| Autor(en) |
Titel |
Quelle |
Links |
| Salama A, Gaedicke G |
Autoimmunhaemolytische Anaemien. [+] |
In: Helmut Gadner, Gerhard Gaedicke, Charlotte Niemeyer (Hrsg.): Pädiatrische Hämatologie und Onkologie 2005, p.147 |
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| Die autoimmunhämolytischen Anämien sind bei Kindern selten. Wenn sie auftreten, sind sie meistens durch eine akute und schwere Hämolyse gekennzeichnet. Wichtigster diagnostischer Test ist neben dem Blutbild der positive direkte Coombs-Test. Nach dem Reaktionsoptimum der Autoantikörper unterscheidet man Wärmeautoantikörper und Kälteautoantikörper. In der Regel sind die autoimmunhämolytischen Anämien sekundäre Erkrankungen, so dass nach primären Grunderkrankungen, besonders solchen aus dem Formenkreis der Autoimmunerkrankungen und nach Immundefekten, gesucht werden muß. Auch im Rahmen von Infektionen können sie auftreten. Medikamentös induzierte Formen sind bei Kindern selten. Für eine adäquate Behandlung ist eine enge Zusammenarbeit zwischen Klinik und Transfusionsmedizin erforderlich, zumal sich die Transfusionstherapie, vor allem im Initialstadium, schwierig gestalten kann. |
| Salzburg J, Burkhardt B, Zimmermann M, Wachowski O, Woessmann W, Oschlies I, Klapper W, Wacker HH, Ludwig WD, Niggli F, Mann G, Gadner H, Riehm H, Schrappe M, Reiter A |
Prevalence, clinical pattern, and outcome of CNS involvement in childhood and adolescent non-Hodgkin's lymphoma differ by non-Hodgkin's lymphoma subtype: a Berlin-Frankfurt-Münster Group Report. |
Journal of clinical oncology 2007, 25: 3915 |
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| Salama A, Kiesewetter H, Kalus U, Movassaghi K, Meyer O |
Massive platelet transfusion is a rapidly effective emergency treatment in patients with refractory autoimmune thrombocytopenia. [+] |
Thrombosis and haemostasis 2008, 100: 762 |
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| Patients with refractory autoimmune thrombocytopenia (ITP) may develop life-threatening bleeding that cannot be immediately controlled by drug administration. To date, there have been no studies conducted to evaluate the efficacy of platelet transfusion alone in such cases. Ten patients with refractory ITP and bleeding or a high bleeding risk were consecutively transfused (one unit/30 min) with apheresis platelet concentrates (APC) without the administration of new drugs. The used APCs (average 3-7 units) contained 2.7 x 10(11) (medium) platelets and were leukodepleted (< or = 1 x 10(6) leukocytes/unit). Platelet serology was performed using standard techniques. Platelet transfusion resulted in an increase in the platelet count to 84 - 157 x 10(3)/microl, and the cessation of bleeding in all patients without any serious adverse effects. Although platelet counts gradually decreased within a few days post-transfusion, bleeding was stopped in all cases. These findings indicate that consecutive platelet transfusion using APCs is a rapidly effective emergency treatment in patients with refractory ITP. |
| Sander A, Zimmermann M, Dworzak M, Fleischhack G, von Neuhoff C, Reinhardt D, Kaspers GJ, Creutzig U |
Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials. [+] |
Leukemia 2010, |
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| Relapse remains the major cause of treatment failure in pediatric acute myeloid leukemia (AML). We analyzed the clinical characteristics, treatment response to relapse treatment and overall survival (OS) of 379 children with AML relapse treated according to three consecutive frontline protocols of the AML-Berlin/Frankfurt/Muenster study group (AML-BFM-87/-93/-98). Of 313 treated patients with data on remission status, 198 children (63%) achieved a second complete remission (CR2). There were no significant differences in remission rates and OS for the intensive reinduction treatment schedules used. The 5-year OS rate was 23% for the total group and 29% for patients treated with curative intent. OS rates increased with study periods from 18 to 34% (P(log rank)=0.012), whereas the proportion of patients receiving only palliative treatment decreased from 23 to 11% (P(CMH)=0.005). Late relapse, no allogeneic stem cell transplantation (SCT) in CR1, age <10 years and favorable cytogenetics were independent favorable prognostic factors for survival. Achievement of CR2 was the most important prognostic factor (OS 44 vs 3%; P(log rank)<0.0001). Overall, one-third of children with relapsed AML can be cured today. SCT in CR2 is recommended for most patients, although its impact on CR2 is discussed.Leukemia advance online publication, 10 June 2010; doi:10.1038/leu.2010.127. |
| Sasco AJ, Vainio H |
From in utero and childhood exposure to parental smoking to childhood cancer: a possible link and the need for action. |
Hum Exp Toxicol 1999, 18: 192 |
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| Satge D, Sasco A, Carlsen N, Stiller C, Rubie H, Hero B, De Bernardi B, de Kraker J, Coze C, Kogner P, Langmark F, Hakvoort-Cammel F, Beck D, von der Weid, Parkes S, Hartmann O, Lippens R, Kamps W, Sommelet D |
A lack of neuroblastoma in Down syndrome. |
Cancer Res 1998, 58: 448 |
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| Sauerbrey A, Bielack S, Kempf-Bielack B, Zoubek A, Paulussen M, Zintl F |
High-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (ASCT) as salvage therapy for relapsed osteosarcoma. |
Bone Marrow Transplant 2001, 27: 933 |
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| Scheer U, Schellong G |
The prognostic value of measuring cell size in acute childhood leukemia (author's transl). |
Klin Pädiatr 1979, 191: 127 |
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| Scheer U, Schellong G, Riehm H |
Verbesserte Prognose der akuten myeloischen Leukämien bei Kindern nach intensivierter Anfangstherapie. |
Klinische Pädiatrie 1979, 191: 210 |
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| Schellong G, Waubke A, Langermann H, Breu H, Kuhne B, Riehm H, Ritter J |
Significance of clinical and intraoperative findings for the prediction of splenic involvement in children with Hodgkin's disease. |
Klin Pädiatr 1982, 194: 242 |
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| Schellong G, Creutzig U, Ritter J |
Treatment of acute myelogenous leukemia in children. |
Med Oncol Tumor Pharmacother 1985, 2: 17 |
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| Schellong G, Bramswig J, Ludwig R, Gerein V, Jobke A, Jürgens H, Kabisch H, Stollmann B, Weinel P, Gadner H, |
Combined treatment strategy in over 200 children with Hodgkin's disease. |
Klin Pädiatr 1986, 198: 137 |
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| Schellong G, Lietzke S, Strauch S, Kuhne B, Schneider B |
Results of ultrasonic, computer tomography and clinical findings for the detection of abdominal involvement in Hodgkin's disease in childhood--a retrospective statistical analysis of 145 patients in the therapeutic study DAL-HD-82. |
Klin Pädiatr 1986, 198: 147 |
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| Schellong G, Waubke-Landwehr A, Langermann H, Riehm H, Bramswig J, Ritter J |
Prediction of splenic involvement in children with Hodgkin's disease. Significance of clinical and intraoperative findings. A retrospective statistical analysis of 154 patients in the German therapy study DAL-HD- 78. |
Cancer 1986, 57: 2049 |
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| Schmidt RF, Thews G (Hrsg) |
Physiologie des Menschen. |
Springer Verlag 23. Aufl. 1987 |
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| Schellong G, Bramswig J, Schwarze E, Wannenmacher M |
An approach to reduce treatment and invasive staging in childhood Hodgkin's disease. |
Bull Cancer 1988, 75: 41 |
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| Schellong G, Hornig I, Bramswig J, Bokkerink J, Steinhoff A, Ludwig R, Niethammer D, Reiter A, von Lengerke H, Heinecke H, Schwarze E, Pötter R, Müller R, Wannenmacher M, |
Significance of procarbazine in the chemotherapy of Hodgkin's disease-- a report of the Cooperative Therapy Study DAL-HD-85. |
Klin Pädiatr 1988, 200: 205 |
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| Schellong G, Hornig I, Schwarze E, Wannenmacher M |
Risk factor adapted treatment of Hodgkin's lymphoma in childhood. |
Recent Results Cancer Res 1989, 117: 205 |
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| Schellong G, Brämswig J, Hörnig-Franz I |
Treatment of children with Hodgkin's disease--results of the German Pediatric Oncology Group. |
Ann Oncol 1992, 3 Suppl 4: 73-6: 73 |
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| Scholz R, Kabisch H, Weber B, Roser K, Delling G, Winkler K |
Studies of the RB1 gene and the p53 gene in human osteosarcomas. |
Pediatr Hematol Oncol 1992, 9: 125 |
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| Schwerdtfeger R, Schmid H, Zingsem J, Beck J, Bender-Götze C, Döpfer R, Peters H, Henze G, Siegert W |
High-dose VP-16 and fractionated total body irradiation followed by autologous bone marrow transplantation in children with relapsed or high-risk acute lymphoblastic leukemia. |
Haematol Blood Transfus 1992, 34: 568 |
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| Schmid H, Henze G, Schwerdtfeger R, Baumgarten E, Besserer A, Scheffler A, Serke S, Zingsem J, Siegert W |
Fractionated total body irradiation and high-dose VP-16 with purged autologous bone marrow rescue for children with high risk relapsed acute lymphoblastic leukemia. |
Bone Marrow Transplant 1993, 12: 597 |
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| Schmidt D, Wischmeyer P, Leuschner I, Sprenger E, Langenau E, von Schweinitz D, Harms D |
DNA analysis in hepatoblastoma by flow and image cytometry. |
Cancer 1993, 72: 2914 |
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| Schneider S, Wildhardt G, Ludwig R, Royer-Pokora B |
Exon skipping due to a mutation in a donor splice site in the WT-1 gene is associated with Wilms' tumor and severe genital malformations. |
Hum Genet 1993, 91: 599 |
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| Schrappe M |
Acute leukemia in children. |
Kinderkrankenschwester 1993, 12: 106 |
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| Schellong G, Brämswig J, Hörnig-Franz I, Schwarze E, Pötter R, Wannenmacher M |
Hodgkin's disease in children. |
Ann Oncol 1994, 5 Suppl 2: 113-5: 113 |
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| Schellong G, Hornig-Franz I, Rath B, Ritter J, Riepenhausen M, Kabisch H, Goldschmitt-Wuttge B, Schmidt P, Niethammer D, Gaedicke G, Schwarze E, Pötter R, |
Reducing radiation dosage to 20-30 Gy in combined chemo-/radiotherapy of Hodgkin's disease in childhood. A report of the cooperative DAL-HD- 87 therapy study. |
Klin Pädiatr 1994, 206: 253 |
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| Schellong G, Hörnig-Franz I, Rath B, Ritter J, Riepenhausen M, Kabisch H, Goldschmitt-Wuttge B, Schmidt P, Niethammer D, Gaedicke G |
Reducing radiation dosage to 20-30 Gy in combined chemo-/radiotherapy of Hodgkin's disease in childhood. A report of the cooperative DAL-HD-87 therapy study. |
Klin Pädiatr 1994, 206: 253 |
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| Schmid H, Schwerdtfeger R, Henze G, Baumgarten E, Besserer A, Scheffler A, Gallardo J, Schmidt-Wolf I, Schwella N, Zingsem J, Siegert W |
Autologous and allogeneic bone marrow transplantation after identical high-dose chemo-radiotherapy in children with relapsed ALL. |
Haematol Blood Transfus 1994, 721 |
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| Schrappe M, Reiter A, Sauter S, Ludwig W, Wormann B, Harbott J, Bender-Gotze C, Dörffel W, Dopfer R, Frey E, |
Concept and interim result of the ALL-BFM 90 therapy study in treatment of acute lymphoblastic leukemia in children and adolescents. |
Klin Pädiatr 1994, 206: 208 |
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| Schweizer P |
Das Rhabdomyosarkom. |
Kinderheilkunde 1994, 10 |
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| Schweizer P |
Resectability of malignant soft tissue tumors. Retrospective analysis of patients in the CWS 86 study. |
Klinische Pädiatrie 1994, 206: 263 |
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| Schwella N, Schwerdtfeger R, Konig V, Blasczyk R, Schmid H, Schmidt-Wolf I, Henze G, Siegert W |
Allogeneic bone marrow transplantation for recurrence of leukemia after autologous bone marrow transplantation. |
Transplantation 1994, 57: 1263 |
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| Scheurlen W, Krauss J, Kühl J |
No preferential loss of one parental allele of chromosome 17p13. 3 in childhood medulloblastoma. |
Int J Cancer 1995, 63: 372 |
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| Schoch C, Rieder H, Freund M, Hoelzer D, Riehm H, Fonatsch C |
Twenty-three cases of acute lymphoblastic leukemia with translocation t(4;11)(q21;q23). |
Annals Hematology 1995, 70: 195 |
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| Schellong G |
The balance between cure and late effects in childhood Hodgkin's lymphoma. |
Ann Oncol 1996, 7 Suppl 4: 67 |
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| Schellong G |
Treatment of children and adolescents with Hodgkin's disease. |
Baillieres Clin Haematol 1996, 9: 619 |
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| Schellong G, Riepenhausen M, Creutzig U, Ritter J, Harbott J, Mann G, Gadner H, Group for |
Incidence of Secondary Leukemias After Therapy of Childhood Hodgkin's Disease Without Nitrogen-Mustard. Results of the German-Austrian Study Group. |
Haematology and Blood Transfusion 1996, 38: 898 |
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| Scheurlen W, Sörensen N, Roggendorf W, Kühl J |
Molecular analysis of medulloblastomas occurring simultaneously in monozygotic twins. |
Eur J Pediatr 1996, 155: 880 |
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| Schlehofer B, Blettner M, Geletneky K, Haaf H, Kaatsch P, Michaelis J, Mueller-Lantzsch N, Niehoff D, Winkelspecht B, Wahrendorf J, Schlehofer J |
Sero-epidemiological analysis of the risk of virus infections for childhood leukaemia. |
Int J Cancer 1996, 65: 584 |
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| Schlieben S, Borkhardt A, Reinisch I, Ritterbach J, Janssen J, Ratei R, Schrappe M, Repp R, Zimmermann M, Kabisch H, Janka-Schaub G, Bartram C, Ludwig W, Riehm H, Lampert F, Harbott J |
Incidence and clinical outcome of children with BCR/ABL-positive acute lymphoblastic leukemia (ALL). A prospective RT-PCR study based on 673 patients enrolled in the German pediatric multicenter therapy trials ALL-BFM-90 and CoALL-05-92. |
Leukemia 1996, 10: 957 |
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| Schrappe M, Reiter A, Riehm H |
Cytoreduction and prognosis in childhood acute lymphoblastic leukemia. |
J Clin Oncol 1996, 14: 2403 |
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| Schellong G, Riepenhausen M, Creutzig U, Ritter J, Harbott J, Mann G, Gadner H |
Low risk of secondary leukemias after chemotherapy without mechlorethamine in childhood Hodgkin's disease. German-Austrian Pediatric Hodgkin's Disease Group. |
J Clin Oncol 1997, 15: 2247 |
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| Scheurlen W, Seranski P, Mincheva A, Kühl J, Sörensen N, Krauss J, Lichter P, Poustka A, Wilgenbus K |
High-resolution deletion mapping of chromosome arm 17p in childhood primitive neuroectodermal tumors reveals a common chromosomal disruption within the Smith-Magenis region, an unstable region in chromosome band 17p11. 2 |
Genes Chromosomes Cancer 1997, 18: 50 |
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| Schrappe M, Creutzig U |
Akue lymphoblastische (ALL) und akute myeloblastische (AML) Leukämie, in Creutzig U, Henze G (Hrsg.) |
Diagnostische und therapeutische Standards in der Pädiatrischen Onkologie, München, Bern, Wien, New York, W Zuckschwerdt Verlag 1997 |
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| Schrappe M, Reiter A |
Maligne Non-Hodgkin-Lymohome im Kindesalter, in Schmoll H-J, Höffken, K, Possinger K, (Hrsg.) |
Kompendium Internistische Onkologie, Berlin, Springer 1997, 1713 |
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| Schrappe M, Reiter A, Welte K, Ludwig W, Harbott J, Lampert F, Henze G, Riehm H |
Risk adapted treatment in childhood acute lymphoblastic leukemia:data from the Berlin-Frankfurt-Münster group. |
Haematology and Blood Transfusion 1997 |
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| Schrappe M, Riehm H |
Akute lymphoblastische Leukämie im Kindesalter in Schmoll,H-J, Höffken K,Possinger K (Hrsg.): |
Kompendium Internistische Onkologie, Berlin, Springer 1997 |
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| Schumacher V, Schneider S, Figge A, Wildhardt G, Harms D, Schmidt D, Weirich A, Ludwig R, Royer-Pokora B |
Correlation of germ-line mutations and two-hit inactivation of the WT1 gene with Wilms tumors of stromal-predominant histology. |
Proc Natl Acad Sci U S A 1997, 94: 3972 |
|
| Schweinitz D |
Hepatoblastom. |
Diagnostische und therapeutische Standards in der Pädiatrischen Onkologie 1997, 76 |
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| Scheurlen WG, Seranski P, Mincheva A, Kühl J, Sörensen N, Krauss J, Lichter P, Poustka A, Wilgenbus KK |
High-resolution deletion mapping of chromosome arm 17p in childhood primitive neuroectodermal tumors reveals a common chromosomal disruption within the Smith-Magenis region, an unstable region in chromosome band 17p11. 2. [+] |
Genes, chromosomes & cancer 1997, 18: 50 |
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| Loss of heterozygosity (LOH) on chromosome arm 17p is the most common genetic aberration in childhood primitive neuroectodermal tumors (PNETs). To determine the frequency and extent of 17p deletions, 29 loci on 17p were investigated in 24 tumors by using restriction fragment length polymorphism (RFLP) and microsatellite analysis. LOH on 17p was found in 9 of 24 tumors. In all tumors with LOH, a continuous stretch from the telomere to chromosome band 17p11.2 was completely deleted, and no interstitial or terminal small-scale deletions were detected in the remaining 15 tumors. In four tumors with LOH on 17p, the chromosomal breakpoint was located between D17S953 and D17S805. To identify this deletion breakpoint on the cytogenetic map of chromosome 17 and to exclude uniparental disomy, we verified our data by using fluorescence in situ hybridization (FISH) analyses. By using two yeast artificial chromosome (YAC) clones that were positive for D17S689 and D17S953, the same breakpoint was confirmed in two specimens of cerebrospinal fluid (CSF) metastases by using FISH on interphase preparations. We demonstrate that, in most childhood PNETs with LOH on 17p, the breakpoint is close to, but not within, the centromere. It varies, and it occurs predominantly between the two markers D17S689 and D17S953, which is an unstable chromosomal region that is deleted or duplicated in the Smith-Magenis syndrome. Because LOH of 17p is associated with the formation of isochromosome 17q in the majority of PNETs, this study provides entry points to determine the molecular nature of this phenomenon. |
| Schilling RF |
Spherocytosis, splenectomy, strokes, and heat attacks. |
Lancet 1997, 350: 1677 |
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| Schellong G |
Pediatric Hodgkin's disease. |
Ann Oncol 1998, 9 Suppl 5:S115-S119 |
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| Scheurlen W, Kühl J |
Current diagnostic and therapeutic management of CNS metastasis in childhood primitive neuroectodermal tumors and ependymomas. |
J Neurooncol 1998, 38: 181 |
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| Scheurlen W, Schwabe G, Joos S, Mollenhauer J, Sörensen N, Kühl J |
Molecular analysis of childhood primitive neuroectodermal tumors defines markers associated with poor outcome. |
J Clin Oncol 1998, 16: 2478 |
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| Schilling F, Berthold F, Erttmann R, Keding G, Michaelis J, Sander J, Treuner J |
Neuroblastom-Früherkennung. Krebsfrüherkennung im Kindesalter. |
Deutsches Ärzteblatt 1998, 95: 1485 |
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| Schilling F, Spix C, Berthold F, Erttmann R, Hero B, Michaelis J, Sander J, Tafese T, Treuner J |
German Neuroblastoma Mass Screening Study at 12 Months of Age. |
Med Pediat Oncol 1998, 31: 435 |
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| Schmandt S, Kühl J |
Chemotherapy as prophylaxis and treatment of meningosis in children less than 3 years of age with medulloblastoma. |
J Neurooncol 1998, 38: 187 |
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| Schneider D, Göbel U |
Erhöhte Werte für Alpha-1-Fetoprotein und humanes Gonadotropin. |
Monatsschr Kinderheilkd 1998, 146: 1094 |
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| Schneider D, Göbel U |
Differentialdiagnostische Bewertung erhöhter Werte für Alpa 1-Fetoprotein und humanes Choriogonadotropin im Kindesalter. |
Tumordiagnose und Therapie 1998, 19: 101 |
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| Schott G, Sperling C, Schrappe M, Ratei R, Martin M, Meyer U, Riehm H, Ludwig W |
Immunophenotypic and clinical features of T-cell receptor gammadelta+ T-lineage acute lymphoblastic leukaemia. |
Br J Haematol 1998, 101: 753 |
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| Schrappe M, Arico M, Harbott J, Biondi A, Zimmermann M, Conter V, Reiter A, Valsecchi M, Gadner H, Basso G, Bartram C, Lampert F, Riehm H, Masera G |
Philadelphia chromosome-positive (Ph+) childhood acute lymphoblastic leukemia. |
Blood 1998, 92: 2730 |
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| Schrappe M, Reiter A, Henze G, Niemeyer C, Bode U, Kühl J, Gadner H, Havers W, Pluss H, Kornhuber B, Zintl F, Ritter J, Urban C, Niethammer D, Riehm H |
Prevention of CNS recurrence in childhood ALL. |
Klin Pädiatr 1998, 210: 192 |
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| Schrappe M, Reiter A, Riehm H |
Prophylaxis and treatment of neoplastic meningeosis in childhood acute lymphoblastic leukemia. |
J Neurooncol 1998, 38: 159 |
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| Scheurlen W, Kühl J |
Current diagnostic and therapeutic management of CNS metastasis in childhood primitive neuroectodermal tumors and ependymomas. [+] |
Journal of neuro-oncology 1998, 38(2-3): 181 |
|
| Metastatic disease is a major problem in the management of the most frequent childhood brain tumors, in ependymoma and primitive neuroectodermal tumors (PNET). Today, contrast enhanced craniospinal MRI and careful analysis of craniospinal fluid are a prerequisite for correct staging of both tumors and imply therapeutic consequences. So far metastatic spread of medulloblastoma and some ependymomas is prevented by conventional chemotherapy and radiotherapy. However, some forms of diffuse metastatic dissemination in medulloblastoma are resistant to conventional therapeutic regimens and require new experimental strategies. |
| Scheurlen WG, Schwabe GC, Joos S, Mollenhauer J, Sörensen N, Kühl J |
Molecular analysis of childhood primitive neuroectodermal tumors defines markers associated with poor outcome. [+] |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1998, 16: 2478 |
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| PURPOSE: The diagnostic and prognostic significance of well-defined molecular markers was investigated in childhood primitive neuroectodermal tumors (PNET). MATERIALS AND METHODS: Using microsatellite analysis, Southern blot analysis, and fluorescence in situ hybridization (FISH), 30 primary tumors and six CSF metastasis specimens were analyzed for loss of heterozygosity (LOH) of chromosomes 1q31, 6q, 9q22, 10q, 11, 16q22, and 17p13.1 and/or high-level amplification of the c-myc gene. Experimental data were compared with clinical stage and outcome. RESULTS: LOH of chromosome 17p13.1 was found most frequently (14 of 30 tumors, six of six CSF metastasis specimens); LOH of chromosomes 10q, 16q22, 11, 6, 9q22, and 1q31 was observed in 20.6%, 20%, 14.3%, 12%, 10%, and 0%, respectively. Eight of 32 tumors and CSF specimens showed amplification of c-myc. All tumors with amplification of c-myc were resistant to therapy and had a fatal outcome (mean survival time, 9.3 months). Tumors that displayed LOH of chromosome 17p were associated with metastatic disease. The prognosis of these tumors was worse only when associated with amplification of c-myc. Three of three patients with LOH of 9q22 relapsed. CONCLUSION: In our study, amplification of c-myc was a poor-prognosis marker in PNET. LOH of chromosome 17p was associated with metastatic disease. Molecular analysis of primary tumors using these markers may be useful for stratification of children with PNET in future prospective studies. The other aberrations investigated were not of significant prognostic value, but may provide an entry point for future large-scale molecular studies. |
| Schellong G, Dörffel W |
Morbus Hodgkin bei Kindern und Jugendlichen. |
Kompendium Internistische Onkologie 1999, 1: 2257 |
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| Schellong G, Potter R, Bramswig J, Wagner W, Prott F, Dörffel W, Körholz D, Mann G, Rath B, Reiter A, Weissbach G, Riepenhausen M, Thiemann M, Schwarze E |
High cure rates and reduced long-term toxicity in pediatric Hodgkin's disease. |
J Clin Oncol 1999, 17: 3736 |
|
| Schmidt B, Koscielniak E, Pilz T, Treuner J |
Radiation therapy in juvenile aggressive fibromatosis. |
Klinische Pädiatrie 1999, 211: 296 |
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| Schneider D, Göbel U |
Diagnostic and therapeutic pitfalls in infants with large sacrococcygeal tumors [letter; comment] [see comments]. |
Pediatr Hematol Oncol 1999, 16: 481 |
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| Schneider D, Hilgenfeld E, Schwabe D, Behnisch W, Zoubek A, Wessalowski R, Göbel U |
Acute myelogenous leukemia after treatment for malignant germ cell tumors in children. |
J Clin Oncol 1999, 17: 3226 |
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| Schuz J, Kaatsch P, Kaletsch U, Meinert R, Michaelis J |
Association of childhood cancer with factors related to pregnancy and birth. |
Int J Epidemiol 1999, 28: 631 |
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| Schuz J, Kaletsch U, Meinert R, Kaatsch P, Michaelis J |
Association of childhood leukaemia with factors related to the immune system. |
Br J Cancer 1999, 80: 585 |
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| Schwartz S, Heinecke A, Zimmermann M, Creutzig U, Schoch C, Harbott J, Fonatsch C, Löffler H, Buchner T, Ludwig W, Thiel E |
Expression of the C-kit receptor (CD117) is a feature of almost all subtypes of de novo acute myeloblastic leukemia (AML), including cytogenetically good-risk AML, and lacks prognostic significance. |
Leuk Lymphoma 1999, 34: 85 |
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| Schweinitz D |
Hepatoblastom. |
Leitlinien Kinderheilkunde 1999 |
|
| Schweinitz D |
Hepatoblastom. |
Onkologisches Daten- und Informationssystem (H Link und H Poliwoda) ODIN 1999 |
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| Schilling F, Berthold F, Erttmann R, Michaelis J, Spix C, Sander J, Schwarz K, Treuner J |
Population-based and controlled study to evaluate neuroblastoma screening at one year of age in Germany. |
Med Pediatr Oncol 2000, 35: 701 |
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| Schilling F, Bihl H, Jacobsson H, Ambros P, Martinsson T, Borgstrom P, Schwarz K, Ambros I, Treuner J, Kogner P |
Combined (111)In-pentetreotide scintigraphy and (123)I-mIBG scintigraphy in neuroblastoma provides prognostic information. |
Med Pediatr Oncol 2000, 35: 688 |
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| Schneider D, Calaminus G, Reinhard H, Gutjahr P, Kremens B, Harms D, Göbel U |
Primary mediastinal germ cell tumors in children and adolescents. |
J Clin Oncol 2000, 18: 832 |
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| Schrappe M, Camitta B, Pui C, Eden T, Gaynon P, Gustafsson G, Janka-Schaub G, Kamps W, Masera G, Sallan S, Tsuchida M, Vilmer E |
Long-term results of large prospective trials in childhood acute lymphoblastic leukemia. |
Leukemia 2000, 14: 2193 |
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| Schrappe M, Reiter A, Ludwig W, Harbott J, Zimmermann M, Hiddemann W, Niemeyer C, Henze G, Feldges A, Zintl F, Kornhuber B, Ritter J, Welte K, Gadner H, Riehm H |
Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy. |
Blood 2000, 95: 3310 |
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| Schrappe M, Reiter A, Zimmermann M, Harbott J, Ludwig W, Henze G, Gadner H, Odenwald E, Riehm H |
Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Berlin-Frankfurt-Münster. |
Leukemia 2000, 14: 2205 |
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| Schulz S, Becker K, Braungart E, Reichmuth C, Klamt B, Becker I, Atkinson M, Gessler M, Hofler H |
Molecular analysis of E-cadherin and cadherin-11 in Wilms' tumours. |
J Pathol 2000, 191: 162 |
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| Schuz J, Grigat J, Stormer B, Rippin G, Brinkmann K, Michaelis J |
Extremely low frequency magnetic fields in residences in Germany. Distribution of measurements, comparison of two methods for assessing exposure, and predictors for the occurrence of magnetic fields above background level. |
Radiat Environ Biophys 2000, 39: 233 |
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| Schuz J, Kaletsch U, Meinert R, Kaatsch P, Michaelis J |
Risk of childhood leukemia and parental self-reported occupational exposure to chemicals, dusts, and fumes. |
Cancer Epidemiol Biomarkers Prev 2000, 9: 835 |
|
| Schwabe J, Francke A, Gerharz C, Willnow U, Schneider D, Nürnberger W |
Immature teratoma arising from an intra-abdominal testis in a 5-month-old boy. |
Med Pediatr Oncol 2000 Aug ;35 (2 ):140 -1 2000, 35: 140 |
|
| Schmitt HJ, Jilg W, Rasch G |
Impfempfehlungen der Ständigen Impfkommission (STIKO) am Robert-Koch-Institut. |
Epidemiologisches Bulletin 2000, 2: 9 |
|
| Schilling F, Ambros P, Bihl H, Martinsson T, Ambros I, Borgstrom P, Jacobsson H, Falkmer U, Treuner J, Kogner P |
Absence of somatostatin receptor expression in vivo is correlated to di- or tetraploid 1p36-deleted neuroblastomas. |
Med Pediatr Oncol 2001, 36: 56 |
|
| Schneider D, Calaminus G, Göbel U |
Diagnostic value of alpha 1-fetoprotein and beta-human chorionic gonadotropin in infancy and childhood. |
Pediatr Hematol Oncol 2001, 18: 11 |
|
| Scholz I, Popp S, Granzow M, Schoell B, Holtgreve-Grez H, Takeuchi S, Schrappe M, Harbott J, Teigler-Schlegel A, Zimmermann M, Fischer C, Koeffler H, Bartram C, Jauch A |
Comparative genomic hybridization in childhood acute lymphoblastic leukemia. |
Cancer Genet Cytogenet 2001, 124: 89 |
|
| Schrappe M |
Workshop on minimal residual disease. |
Leukemia 2001, 15 |
|
| Schrappe M, Creutzig U |
Akute lymphoblastische- (ALL) und akute myeloische (AML) Leukämie im Kindesalter. Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie. |
AWMF online 2001 |
|
| Schuz J, Kaletsch U, Kaatsch P, Meinert R, Michaelis J |
Risk factors for pediatric tumors of the central nervous system. |
Med Pediatr Oncol 2001, 36: 274 |
|
| Schuz J, Kaletsch U, Meinert R, Kaatsch P, Michaelis J |
High-birth weight and other risk factors for Wilms tumour. |
Eur J Pediatr 2001, 160: 333 |
|
| Schuz J, Kaletsch U, Meinert R, Kaatsch P, Spix C, Michaelis J |
Risk factors for neuroblastoma at different stages of disease. Results from a population-based case-control study in Germany. |
J Clin Epidemiol 2001, 54: 702 |
|
| Schneider DT, Schuster AE, Fritsch MK, Calaminus G, Harms D, Göbel U, Perlman EJ |
Genetic analysis of childhood germ cell tumors with comparative genomic hybridization. [+] |
Klinische Padiatrie 2001, 213: 204 |
|
| BACKGROUND: Germ Cell Tumors (GCTs) in children and adolescents constitute a clinically and histologically heterogeneous group of tumors. Compared to GCTs in adults, the numbers of GCTs in children analyzed with cytogenetic and molecular genetic techniques is limited. However, the data available to date reveal a pattern of cytogenetic aberrations different from that in adults. Comparative genomic hybridization (CGH) is a valuable technique for the genetic profiling of tumors that allows screening for chromosomal imbalances consistent with amplification of oncogenes and loss of putative tumor suppressor genes. As CGH does not require tissue culture, it also allows analysing archival tissue samples. PATIENTS: This study focuses exclusively on GCTs in children younger than ten years of age and summarizes the genetic data of 51 tumors. Eighteen teratomas and 33 malignant GCTs were included. Primary sites were the testis (n=10), coccyx (n=13), mediastinum (n=20), ovary (n=5), CNS (n=2), and the face (n=1). METHODS: The experimental procedure includes differential enzymatic fluorescence labeling of tumor and control DNA followed by comparative hybridization to normal male chromosomes, karyotyping and computerized analysis of the fluorescence profiles. RESULTS: With the exception of one testicular and two ovarian tumors, malignant GCTs in children do not show chromosomal gain of 12p, which is characteristic of GCTs in adult patients. Irrespective of the primary site, childhood GCTs show chromosomal imbalances of chromosome 1 (loss of distal 1p, gain of 1q), deletion of 4q and 6q as well as gain of 20q at a high frequency. CONCLUSIONS: These studies will help guiding further investigations elucidating the role of putative tumor suppressor genes at e.g. 1p36 and 6q. In addition, further studies incorporated in prospective therapeutic protocols are necessary to evaluate the prognostic relevance of specific genetic aberrations. |
| Schiller M, Böhm M, Zeidler C, Germeshausen M, Welte K, Luger TA, Bonsmann G |
[Cyclic neutropenia. Detection of a mutation in the gene for neutrophil elastase (ELA2)]. [+] |
Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete 2001, 52: 790 |
|
| Cyclic neutropenia is a rare congenital hematopoietic disease which occurs sporadically or as an autosomal dominantly inherited disorder. Recently, the locus for cyclic neutropenia was mapped to chromosome 19p13.3. Autosomal dominant and sporadic cyclic neutropenia are now attributable to mutations of the ELA2 gene encoding neutrophil elastase. |
| Schilling F, Spix C, Berthold F, Erttmann R, Fehse N, Hero B, Klein G, Sander J, Schwarz K, Treuner J, Zorn U, Michaelis J |
Neuroblastoma screening at one year of age. |
N Engl J Med 2002, 346: 1047 |
|
| Schilling F, Spix C, Berthold F, Erttmann R, Klein G, Sander J, Treuner J |
Neuroblastom-Früherkennung. |
Onkologe 2002, 10: 1103 |
|
| Schilling F, Spix C, Berthold F, Erttmann R, Klein G, Sander J, Treuner J |
Modellprojekt Neuroblastom-Früherkennung - Eine Krebsfrüherkennungsstudie im Kindesalter mit unerwartetem Ausgang. |
Monatschr Kinderheilkd 2002, 150: 934 |
|
| Schuck A, Ahrens S, Konarzewska A, Paulussen M, Frohlich B, Konemann S, Rube C, Rube C, Dunst J, Willich N, Jürgens H |
Hemithorax irradiation for Ewing tumors of the chest wall. |
Int J Radiat Oncol Biol Phys 2002, 54: 830 |
|
| Schuck A, Rube C, Konemann S, Rube C, Ahrens S, Paulussen M, Dunst J, Jürgens H, Willich N |
Postoperative radiotherapy in the treatment of Ewing tumors. |
Strahlenther Onkol 2002, 178: 25 |
|
| Schüz J, Kaatsch P |
Epidemiology of pediatric tumors of the central nervous system. |
Expert Rev Neurotherapeutics 2002, 2: 469 |
|
| Schrappe M, Beier R, Burger B |
New treatment strategies in childhood acute lymphoblastic leukaemia. |
Best Pract Res Clin Haematol 2002, 15: 729 |
|
| Schneider DT, Calaminus G, Wessalowski R, Pathmanathan R, Harms D, Göbel U |
Therapy of advanced ovarian juvenile granulosa cell tumors. [+] |
Klinische Padiatrie 2002, 214: 173 |
|
| BACKGROUND: Gonadal sex cord-stromal tumors are rare tumors that develop from the gonadal non-germ cell component such as granulosa, Sertoli or Leydig cells. Among these, juvenile granulosa cell tumors (JGCT) constitute the largest subgroup of ovarian sex cord-stromal tumors during childhood and adolescence. In local disease (FIGO stage I), the beneficial role of tumor-ovarectomy is well established. In contrast, life expectancy in patients with advanced JGCT (FIGO stage >/= II) is short even after complete tumor resection. The current literature provides only limited and inconclusive data regarding the value of adjuvant chemotherapy in such patients with advanced disease. PATIENTS AND METHODS: Therefore, we analyzed the patients with FIGO stage >/= II JGCT who were prospectively documented as follow-up patients of the German MAKEI trials for non-testicular germ cell tumors and received the recommended cisplatin-based chemotherapy in an adjuvant setting. From 1988 until 2000, 7 patients (age, 4;2 - 18;11 years, median 14;8 years) were registered. Three patients were stage IIc, one stage IIIa, and three stage IIIc. 5 patients underwent laparatomy with adnectomy, which was complete in only two patients. Two patients received laparoscopic tumor resection, which was incomplete in both. All patients received 4 or 6 cycles of adjuvant cisplatin-based three-agent chemotherapy in analogy to the current therapeutic concept applied in malignant germ cell tumors. One patient with a large tumor and multiple peritoneal metastases additionally received 40 Gy abdominal irradiation. RESULTS: All patients achieved complete clinical remission after initial surgery and adjuvant chemotherapy. 4 out of 7 patients are currently remaining in first continuous complete remission after 15 to 111 months follow-up. One patient developed a metachronous tumor of the contralateral ovary after 126 months follow-up and is still alive but currently in therapy of another recurrence. Another patient suffered a tumor recurrence after 12 months but achieved a second complete remission with cisplatin chemotherapy after a follow-up of currently 4 months. One patient achieved complete clinical remission but suffered a diffuse peritoneal tumor recurrence with massive ascites and finally died as a result of tumor progression. In summary, at the time of this report 6 of 7 patients are alive after a median of 47 (15 - 138) months. CONCLUSION: This analysis clearly demonstrates that advanced JGCT can be successfully treated with surgery followed by adjuvant cisplatin-based chemotherapy. Therefore, this study reveals encouraging therapeutic perspectives in these otherwise fatal tumors that merit further investigation in a prospective cooperative trial. |
| Schmidt P, Haas RJ, Göbel U, Calaminus G |
[Results of the German studies (MAHO) for treatment of testicular germ cell tumors in children--an update]. [+] |
Klinische Padiatrie 2002, 214: 167 |
|
| BACKGROUND: The MAHO studies for treatment of testicular germ cell tumors in childhood and adolescence registered between 1982 and 1/2001 260 patients (pts.). Aims of the studies were: 1. Delay of chemotherapy in YST of stage I A. 2. Delay of modified lymphadenectomy for staging in I A tumors. 3. Stepwise reduction of therapy in low stage tumors but increasing therapy in tumors of metastatic pattern. Standard therapy consisted of 4 courses of vinblastine, bleomycin and cisplatin. In stage II C or higher chemotherapy included cisplatin, VP 16 and bleomycin. As salvage therapy VP16, ifosfamide and cisplatin was given. RESULTS: According to histology and stage only 75/260 pts. needed chemotherapy. Out of 140 pts. with YST 139 survived disease free according to a |
| Schwabe J, Calaminus G, Vorhoff W, Engelbrecht V, Hauffa BP, Göbel U |
Sexual precocity and recurrent beta-human chorionic gonadotropin upsurges preceding the diagnosis of a malignant mediastinal germ-cell tumor in a 9-year-old boy. [+] |
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 2002, 13: 975 |
|
| Numerous disorders are known to cause sexual precocity. Beta-human chorionic gonadotropin (beta-HCG)-secreting germ-cell tumors are one of the sources that have to be considered in the differential diagnosis of processes inducing a peripheral precocious puberty. Germ-cell tumors might be located in the ovaries or testes, retroperitoneum, mediastinum or the cranium. We present the case of a 9-year-old boy with sexual precocity and a recurrent transient beta-HCG elevation. After an interval of 2 years with repeated radiological examinations including the mediastinum, a mediastinal tumor was identified by magnetic resonance imaging. To our knowledge, this is the first case of a diagnosis of a mediastinal choriocarcinoma with a recurrent serum beta-HCG elevation. So far, factors that might be responsible for the repeated spontaneous beta-HCG decline are unknown. |
| Schneider DT, Schuster AE, Fritsch MK, Calaminus G, Göbel U, Harms D, Lauer S, Olson T, Perlman EJ |
Genetic analysis of mediastinal nonseminomatous germ cell tumors in children and adolescents. [+] |
Genes, chromosomes & cancer 2002, 34: 115 |
|
| Primary mediastinal germ cell tumors (M-GCTs) represent a heterogeneous group of tumors that varies with regard to age at presentation, histologic differentiation, and outcome. We retrospectively analyzed archival tissue samples of mediastinal mature and immature teratomas (n = 15) and malignant nonseminomatous M-GCTs (n = 20) with comparative genomic hybridization (CGH). The aim of this study was to define distinct genetic subgroups of M-GCT among the pediatric cohort that may differ in their clinical behavior and prognosis. All pure teratomas showed normal CGH profiles. Malignant M-GCTs in infants and children < 8 years old most frequently showed a gain of 1q, 3, and 20q and a loss of 1p, 4q, and 6q. Gain of 12p and sex chromosomal abnormalities were not observed in this age group. In contrast, the gain of 12p was the most common aberration in M-GCTs that arose in children > or = 8 years old. Additional recurrent changes included the loss of chromosome 13 and the gain of chromosome 21. All ten adolescents with malignant M-GCT were male, and five showed a gain of the X chromosome. In two of these five patients, Klinefelter syndrome was confirmed by cytogenetic analysis or by fluorescence in situ hybridization (FISH). In conclusion, CGH analysis of M-GCTs defines distinct genetic subgroups. Mediastinal teratomas show no genetic gains or losses. Malignant M-GCTs in children < 8 years old show the same pattern of gains and losses identified in sacrococcygeal and testicular GCTs at this age, and they lack sex-chromosomal abnormalities. Malignant M-GCTs in children > or = 8 years old show the same genetic profile previously reported in gonadal GCTs at this age. In addition, approximately 50% demonstrate a gain of the X chromosome, consistent with Klinefelter syndrome. Cooperative group studies reveal a significantly better prognosis of malignant M-GCT arising in infants compared to that in adolescents, suggesting that these genetic differences are associated with differences in clinical behavior. |
| Schaeffeler E, Stanulla M, Greil J, Schrappe M, Eichelbaum M, Zanger U, Schwab M |
A novel TPMT missense mutation associated with TPMT deficiency in a 5-year-old boy with ALL. |
Leukemia 2003, 17: 1422 |
|
| Schellong G, Riepenhausen M |
Spätfolgen nach Hodgkinscher Krankheit. |
WIR 2003, 1: 18 |
|
| Schilling F, Spix C, Berthold F, Erttmann R, Klein G, Sander J, Treuner J, Michaelis J |
Neuroblastom-Früherkennung im Alter von einem Jahr in Deutschland. |
Deutsches Ärzteblatt 2003, 25: 1442 |
|
| Schiltmeyer B, Hempel G, Schwab M, Ritter C, Klingebiel T, Boos J |
Population pharmacokinetics of oral busulfan in children. |
Int J Clin Pharmacol Ther 2003, 40: 385 |
|
| Schrappe M |
Prognostic factors in childhood acute lymphoblastic leukemia. |
Indian J Pediatr 2003, 70: 817 |
|
| Schrappe M, Beier R, Burger B |
New treatment strategies in childhood acute lymphoblastic leukaemia. |
Best Pract Res Clin Haematol 2003, 15: 729 |
|
| Schrappe M, Zimmermann M, Stanulla M, Schrauder A |
Stratifizierung der ALL mit Hilfe des Nachweises minimaler Resterkrankung , Rationale und klinische Rationalisierung. |
Monatsschrift Kinderheilkunde 2003, 2: 138 |
|
| Schuck A, Ahrens S, Paulussen M, Kuhlen M, Konemann S, Rube C, Winkelmann W, Kotz R, Dunst J, Willich N, Jürgens H |
Local therapy in localized Ewing tumors: results of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials. |
Int J Radiat Oncol Biol Phys 2003, 55: 168 |
|
| Schuz J, Morgan G, Bohler E, Kaatsch P, Michaelis J |
Atopic disease and childhood acute lymphoblastic leukemia. |
Int J Cancer 2003, 105: 255 |
|
| Schwab M, Westermann F, Hero B, Berthold F |
Neuroblastoma. |
Lancet Oncol 2003, 4: 472 |
|
| Schilling FH, Spix C, Berthold F, Erttmann R, Sander J, Treuner J, Michaelis J |
Children may not benefit from neuroblastoma screening at 1 year of age. Updated results of the population based controlled trial in Germany. [+] |
Cancer letters 2003, 197(1-2): 19 |
|
| Neuroblastoma is the second most frequent malignancy in childhood. We investigated whether screening for neuroblastoma at 1 year of age reduces the incidence of metastatic disease or mortality. Screening was offered in 6 of the 16 German states from 1995 to 2000 with the remaining states serving as controls. We studied 2,581,188 children in the screening area born between 1994 and 1999 and 2,117,600 in the control area. We compared mortality from neuroblastoma and the incidence of disseminated disease in the two groups. The screened group and the control group had similar rates of stage 4 neuroblastoma and mortality due to neuroblastoma. Comparison of the screened group and the control area revealed substantial over diagnosis in the screened participants. The present findings provide no support for mass screening for neuroblastoma at 1 year of age. |
| Schueler AO, Jurklies C, Heimann H, Wieland R, Havers W, Bornfeld N |
Thermochemotherapy in hereditary retinoblastoma. [+] |
Br J Ophthalmol 2003, 87: 90 |
|
| BACKGROUND/AIM: The combination of chemotherapy and transpupillary thermotherapy, thermochemotherapy (TCT) has become an established part of the treatment plan in advanced retinoblastoma. The aim of this study was to identify safe indications, the complications as well as the limitations of this new treatment for retinoblastoma. METHODS: Tumour response and side effects of TCT with an indirect laser ophthalmoscope (spot size about 400 micro m) in 55 tumours of 26 children with bilateral retinoblastoma were analysed. Using the Reese-Ellsworth classification system, nine of 35 eyes were classified as type I, 13 eyes as type II, 10 eyes as type III, and three eyes as type V. The mean age of the children was 0.74 (SD 0.61) years. The mean tumour height was 3.5 (2.3) mm with a mean diameter of 6.1 (4.1) mm. Treatment parameters were 4.3 (1.6) (median 5) thermochemotherapy sessions with a mean energy of 539 (211) mW and a mean duration of 13.5 (5.6) minutes. Chemotherapy courses (vincristine, etoposide, and carboplatin) were repeated every 3 weeks. The mean follow up period was 1.25 (0.6) years. RESULTS: Local recurrence occurred in 21 tumours (38%), with a mean onset of 3.2 (2.9) months after TCT. The risk of tumour recurrence was correlated with tumour height. The recurrence rate was 17% for tumours with a height less than 2 mm, 37% for tumours with a height between 2 and 4 mm, and 63% for larger retinoblastomas. Multivariate analysis identified fish flesh regression after TCT (p = 0.0007) as the most important risk factor for tumour recurrence besides tumour height (p = 0.001) and the necessity of increased laser power during TCT sessions (p = 0.018). Complications during therapy included transient corneal opacification in two eyes (6%), focal iris atrophy (three eyes, 8.5%), peripheral lens opacity (two eyes, 6%), circumscribed transient retinal detachment (one eye, 3%) and diffuse choroidal atrophy (one eye, 3%). CONCLUSION: TCT using an indirect laser ophthalmoscope with a spot size of about 400 micro m was efficient for retinoblastoma with a tumour height less than 4 mm. In larger tumours, the recurrence rate was unacceptably high. Fish flesh regression after TCT correlates with a higher rate of local tumour recurrence. Treatment related complications occurred in less than 9% of the treated eyes. |
| Schneider DT, Jänig U, Calaminus G, Göbel U, Harms D |
Ovarian sex cord-stromal tumors--a clinicopathological study of 72 cases from the Kiel Pediatric Tumor Registry. [+] |
Virchows Archiv : an international journal of pathology 2003, 443: 549 |
|
| We analyzed 72 patients with ovarian sex cord-stromal tumors (OSCST) registered at the German Pediatric Tumor Registry in Kiel over a 20-year period. Juvenile granulosa cell tumors (JGCT, n=48) were the most frequent histological subtype. In addition, there were 14 Sertoli-Leydig cell tumors, 5 sclerosing stromal tumors, 2 sex cord tumors with annular tubules, 2 thecomas and 1 steroid cell tumor. Stage according to FIGO (International Federation of Gynecologists and Obstetricians) was Ia in 39 patients, Ic in 17 patients, II in 3 patients and III in 1 patient (60 patients with complete data). Compared with adult granulosa cell tumors, JGCT showed pronounced mitotic activity [mean 9.8 mitoses/10 high power field (HPF)], which was significantly higher than in other histological subtypes (2.7/10 HPF, P=0.001). Immunohistochemical analysis revealed frequent coexpression of vimentin (positive in 52/52 examined tumors), cytokeratin (27/33), and inhibin (19/20). Of patients, 12 with Ic or higher stage tumors received adjuvant cisplatinum-based chemotherapy. Event-free survival at 10 years was 0.88 +/- 0.05 (38/43 patients with follow-up data). Outcome significantly correlated with stage and mitotic activity (<20 versus > or =20 mitoses/10 HPF: event-free survival 1.0 versus 0.48 +/- 0.05, P=0.0001). In conclusion, this analysis confirms that the majority of patients with OSCST present at low tumor stage and that prognosis in these patients is excellent. Refractory tumors are characterized by high proliferative activity. Therefore, histopathological evaluation substantially contributes to risk assessment in patients with OSCST and might be useful for therapy stratification in prospective therapeutic protocols. |
| Schenk J, Engelmann D, Rohrschneider W, Zieger B, Semler O, Graf N, Troger J |
Rhabdoid tumors of the kidney in childhood. |
Rofo 2004, 176: 965 |
|
| Schrappe M |
Evolution of BFM trials for childhood ALL. |
Annals Hematology 2004, 83 Suppl 1:S121-S123 |
|
| Schuck A, Mattke A, Schmidt B, Kunz D, Harms D, Knietig R, Treuner J, Koscielniak E |
Group II rhabdomyosarcoma and rhabdomyosarcomalike tumors. |
J Clin Oncol 2004, 22: 143 |
|
| Schellong G |
Verhütung und Behandlung schwerer bakterieller Infektionen bei milzlosen Personen – Informationen und Empfehlungen für Ärzte und Patienten. |
Eigenverlag |
|
| Schellong G, Riepenhausen M |
Late effects after therapy of Hodgkin's disease: update 2003/04 on overwhelming post-splenectomy infections and secondary malignancies. [+] |
Klinische Padiatrie 2004, 216: 364 |
|
| BACKGROUND: For a long time, a main focus of paediatric therapy studies for Hodgkin's disease (HD) has been on diminishing adverse late effects. Consequently, the long-term follow-up of patients after HD is very important. The HD late effects project of the GPOH, which evolved from 5 consecutive German-Austrian DAL therapy studies, was aimed at establishing a basis for the further improvement of therapy concepts and of long-term surveillance. PATIENTS AND METHODS: The original cohort consisted of 1 245 study patients from 92 centres enrolled in the DAL studies HD-78 to HD-90 between 1978 and 1995. Initially, follow-up data were submitted by the participating study centres. When the majority of the patients had reached adult age and were no longer seen by the originally treating paediatric colleagues, we contacted them directly by mail every 2-3 years. At the time of analysis (March 2004) information from the preceding 6 years was available in 78.6 % of the patients alive. RESULTS: The median follow-up period of patients at the date of last information was 11.1 years (max. 25.5 years), the median age was 23.7 years (max. 41.1 years). The present report is focused on three out of a wide range of problems evaluated, namely cause of death in 14 patients expired after 10-21 years' follow-up, overwhelming post-splenectomy infections (18 events, 11 fatal), and 46 secondary malignancies. The OS rate after 24 years is 87 % (SE 3 %) in the total group, 83 % (SE 3 %) in 335 asplenic patients, and 93 % (SE 2 %) in 910 non- or partially splenectomised patients. We have initiated activities to improve the prophylactic measures against overwhelming infections in this risk group of asplenic patients. The cumulative incidences of secondary malignancies (SM) after 22 years is 11 % (SE 2 %) for all SM, 10 % (SE 2 %) for solid tumours, 0.8 % (SE 0.5 %) for NHL, and 0.6 % (SE 0.3 %) for leukaemias. The cumulative incidence of breast cancer in female patients at the age of 35 years is 4.0 % (SE 2 %). The effect of reducing the radiotherapy doses in the studies HD-87/HD-90 will become evident within the next years. |
| Schenk JP, Waag KL, Graf N, Wunsch R, Jourdan C, Behnisch W, Troger J, Gunther P |
[3D-visualization by MRI for surgical planning of Wilms tumors]. [+] |
RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin 2004, 176: 1447 |
|
| PURPOSE: To improve surgical planning of kidney tumors in childhood (Wilms tumor, mesoblastic nephroma) after radiologic verification of the presumptive diagnosis with interactive colored 3D-animation in MRI. MATERIALS AND METHODS: In 7 children (1 boy, 6 girls) with a mean age of 3 years (1 month to 11 years), the MRI database (DICOM) was processed with a raycasting-based 3D-volume-rendering software (VG Studio Max 1.1/Volume Graphics). The abdominal MRI-sequences (coronal STIR, coronal T1 TSE, transverse T1/T2 TSE, sagittal T2 TSE, transverse and coronal T1 TSE post contrast) were obtained with a 0.5T unit in 4 - 6 mm slices. Additionally, a phase-contrast-MR-angiography was applied to delineate the large abdominal and retroperitoneal vessels. A notebook was used to demonstrate the 3D-visualization for surgical planning before surgery and during the surgical procedure. RESULTS: In all 7 cases, the surgical approach was influenced by interactive 3D-animation and the information found useful for surgical planning. Above all, the 3D-visualization demonstrates the mass effect of the Wilms tumor and its anatomical relationship to the renal hilum and to the rest of the kidney as well as the topographic relationship of the tumor to the critical vessels. One rupture of the tumor capsule occurred as a surgical complication. For the surgeon, the transformation of the anatomical situation from MRI to the surgical situs has become much easier. CONCLUSION: For surgical planning of Wilms tumors, the 3D-visualization with 3D-animation of the situs helps to transfer important information from the pediatric radiologist to the pediatric surgeon and optimizes the surgical preparation. A reduction of complications is to be expected. |
| Schuck A, Kuhlen M, von Schorlemer L, Ahrens S, Hunold A, Konemann S, Dunst J, Winkelmann W, Jürgens H, Willich N |
Radiotherapy in Ewing's tumors of the vertebral column - Results and analysis of local recurrences. |
STRAHLENTHERAPIE UND ONKOLOGIE 180: 24-24 Suppl. 1, JUN 2004 |
|
| Schneider DT, Calaminus G, Koch S, Teske C, Schmidt P, Haas RJ, Harms D, Göbel U |
Epidemiologic analysis of 1,442 children and adolescents registered in the German germ cell tumor protocols. [+] |
Pediatric blood & cancer 2004, 42: 169 |
|
| BACKGROUND: Germ cell tumors (GCTs) constitute a heterogeneous group of tumors that significantly vary with respect to their clinical presentation and biology. The objective of this analysis was to analyze a large population-based pediatric cohort of GCTs and to evaluate the parameters age, sex, site of the tumor, histology, and potential correlations between these parameters. PROCEDURE: Between 1981 and 2000, 1,442 patients were prospectively enrolled onto the German protocols for testicular and non-testicular GCTs. Tumors were histologically classified according to the WHO. RESULTS: We observed a bimodal age distribution with a first peak during infancy and a second after the onset of puberty. At birth, almost all tumors were teratomas, sometimes with microfoci of yolk sac tumor, which on the other hand, was the predominant histology during childhood. After the onset of puberty, germinomatous GCTs represented the most frequent histological subtype, and malignant non-germinomatous GCTs often presented as mixed tumors with choriocarcinoma and embryonal carcinoma components. During infancy, non-gonadal GCTs accounted for the majority of GCTs, while after the onset of puberty, gonadal GCTs predominated. Notably, among non-gonadal GCTs, there was a female predominance during childhood and a strong male predominance during adolescence. CONCLUSIONS: Two separate groups of GCTs with distinct clinical features relevant for differential diagnosis and the diagnostic assessment can be distinguished. This observation correlates with genetic studies that reveal different genetic changes in childhood and adolescence GCTs. Further studies are needed to elucidate the molecular mechanisms of germ cell and GCT development that account for the age- and sex-dependent clinical manifestation. |
| Schuster FR, Simon A, Laws HJ, Beutel K, Groll AH, Jäger G, Schuster V |
Viral Infections in Pediatric Cancer Patients. |
Klin Pädiatr 2005, 217 Suppl 1:S67 |
|
| Schumacher-Kuckelkorn R, Hero B, Ernestus K, Berthold F |
Lacking immunocytological GD2 expression in neuroblastoma: report of 3 cases. [+] |
Pediatric blood & cancer 2005, 45: 195 |
|
| Immunocytological bone marrow assessment for contamination with neuroblastoma cells is based on their characteristic GD2 surface staining. Neuroblastoma without GD2 expression have been rarely and only after antibody therapy reported. Conventional cytology was performed using Pappenheim staining. For immunocytology, the APAAP method was utilized with the 14G2a anti-GD2 mouse monoclonal antibody. 7 x 10(5) cells on cytospin preparations were investigated. In 2003, 288 bone marrow samples from 191 neuroblastoma patients were investigated by cytology and immunocytology. Three cases demonstrated GD2 negativity on cytologically unambiguous neuroblastoma cells. Two female cases (94 and 37 months of age) with stage 4 neuroblastoma had GD2 expressing neuroblastoma cells in bone marrow at diagnosis. At 2nd relapse 25 and 23 months after diagnosis and 8 months and 12 months after anti-GD2 antibody treatment (ch14.18), the bone marrow infiltrating neuroblastoma cells lacked GD2 staining. The third patient, a 63-month-old girl with bone marrow replacement by neuroblastoma cells showed at diagnosis a mixture of GD2-unstained tumor clumps and very weakly stained neuroblastoma cells. Neuroblastoma cells may lack GD2 expression at diagnosis and at recurrence. This observation has diagnostic and therapeutic implications. |
| Schüz J, Blettner M, Michaelis J, Kaatsch P |
Ursachen von Leukämien im Kindesalter: Resümee einer Fallkontrollstudie des Deutschen Kinderkrebsregisters. |
Dtsch Arztebl 102: A2557-64, 2005. |
|
| Schenk JP, Engelmann D, Zieger B, Semler O, Wuhl E, Furtwangler R, Graf N, Troger J |
[Radiologic differentiation of rhabdoid tumor from Wilms' tumor and mesoblastic nephroma]. [+] |
Der Urologe. Ausg. A 2005, 44: 155 |
|
| Differentiation between rhabdoid tumor (RT) and mesoblastic nephroma (MN) and Wilms' tumor (WT) by imaging studies in babies and young children before histological confirmation is useful to start optimal treatment early. Typical radiologic criteria (crescent-shaped subcapsular liquid areas, tumor lobules, blurred tumor borders, metastasis in the lung, and regional lymph nodes) are described.The results of 26 MRI, 30 CT, and 22 ultrasound examinations of 49 patients (22 RT, 19 WT, and 8 MN, age 2-57 months) were analyzed. The above-mentioned radiologic criteria were classified with score values. The score value distribution was analyzed between the tumor entities and by two investigators.RT had significantly higher score values than the MN and WT. The difference between the two investigators was not significant.As a group RT differentiates from the group of WT and MN, but this is not possible in single cases with the radiologic criteria employed. Only if more signs are observed together in one case can a RT be presumed, which may indicate an early biopsy before chemotherapy. |
| Schlomm T, Gunawan B, Schulten HJ, Sander B, Thangavelu K, Graf N, Leuschner I, Ringert RH, Fuzesi L |
Effects of chemotherapy on the cytogenetic constitution of Wilms' tumor. [+] |
Clinical cancer research 2005, 11: 4382 |
|
| The management of Wilms' tumors consists of a combination of surgery, chemotherapy, and possibly radiotherapy. To date, chemotherapy is being risk stratified according to histologic subtype and stage. Although the cytogenetic characteristics of Wilms' tumors are well established, the cytogenetic effects related to chemotherapy are widely unknown. We herein report on comparative genomic hybridization findings in 41 primary Wilms' tumors of blastemal type, of which 19 had received preoperative chemotherapy (PCT group) and 22 did not (non-PCT group). Overall, imbalances could be detected in 32 tumors, with +1q (17 cases), +7q (10 cases), +7p (6 cases), and -7p (6 cases) as the most common changes. Among these, +7q and -7p were both significantly associated with metastatic disease at the time of surgery (P = 0.002 and 0.007, respectively), and +7q was also associated with higher stage (stages III + IV; P = 0.003). There were significant differences in the cytogenetic constitution of tumors between the two treatment groups. As a trend, tumors in the preoperative-chemotherapy group had fewer changes (mean, 2.7) than those in the non-preoperative-chemotherapy group (mean, 3.8), and the frequencies of imbalances at 7p or +7q, respectively, were significantly lower compared with tumors in the non-preoperative-chemotherapy group (2 of 19 versus 10 of 22, P = 0.019; 1 of 19 versus 9 of 22, P = 0.011). In contrast, -1q was common in both the preop-CT group (10 of 19) and the non-preop-CT group (7 of 22). The results suggest that Wilms' tumor clones with +1q are not obliterated by preoperative chemotherapy, whereas cytogenetically more complex clones with +7q and/or imbalances at 7p seem more responsive and are more likely to be eliminated by chemotherapeutic treatment. |
| Schenk JP, Schrader C, Furtwangler R, Ko HS, Leuschner I, Graf N, Troeger J |
[MRI-morphology and staging of congenital mesoblastic nephroma: evaluation of a collection with 20 patients]. [+] |
RoFo 2005, 177: 1373 |
|
| PURPOSE: To differentiate classic and cellular type of congenital mesoblastic nephroma (CMN) in MRI and to evaluate MRI for staging according to the Societe Internationale de Oncologie Pediatrique (SIOP). MATERIAL AND METHODS: MRI examinations of 20 children with CMN (age 1st to 16th months, classic type n = 11, cellular type n = 7, mixed type n = 2) were analyzed retrospectively. Cysts, necrosis, hemmorhage in the tumor, signal intensity, tumor structure, thrombosis and dilatation of renal vein, crossing of the body midline, peripheral contrast-enhancement, tumor volume and existence of a tumor pseudocapsule in contrast to the residual kidney were described. The radiologic stage was compared with the histopathologic stage (infiltration of perirenal fat and infiltration of the renal sinus). RESULTS: Tumors of the classic type (mean volume 67.9 ml) had necrosis in 1 case, crossed the midline in 1 case, had no cysts or bleeding, and had a peripheral contrast-enhancement in 1 case, and were heterogeneous in 9 cases. The cellular type (mean volume 302.8 ml) had tumor necrosis in 6 cases, bleeding in 3 cases, cysts in 3 cases, crossed the midline in 4 cases, and peripheral contrast enhancement in 2 cases, and was predominantly heterogeneous. Mixed tumor types (7 ml and 202 ml) had tumor necrosis in 1 case and crossed the midline in 1 case, a peripheral contrast enhancement in 2 cases and a homogenous structure in 1 case. The signal intensity in T1 w and T2 w images was not specific. The renal vein was inconspicuous in all children. The evaluation of the infiltration in perirenal fatty tissue was true positive in 1 case, true negative in 10 cases, false negative in 4 cases and false positive in 5 cases. The infiltration of the renal hilus was true positive in 10 children, false positive in 8 cases and true negative in 2 cases. CONCLUSION: A typical finding of CMN in MRI is a heterogeneous tumor without demarcation from the rest of the kidney parenchyma by a pseudocapsule. The cellular type of CMN tends to have a higher tumor volume and shows more necrosis, bleeding and cysts than the classic type in MRI. A peripheral contrast-enhancement in MRI is not characteristic for any type of CMN. Local tumor staging is not possible with MRI. |
| Schenk JP, Gunther P, Schrader C, Ley S, Furtwangler R, Leuschner I, Edelhauser M, Graf N, Troger J |
[Childhood kidney tumors - the relevance of imaging.] [+] |
Der Radiologe 2005, 45: 1112 |
|
| Kidney tumors represent 6.2% of malignant tumors in children. History, clinical course and radiological findings are necessary elements in the differential diagnosis of the different renal tumors. In the case of nephroblastoma, chemotherapy is based solely on the radiological diagnosis without prior histology. In therapy-optimizing studies of the Society of Pediatric Oncology and Hematology, preoperative chemotherapy is performed. Therapy monitoring is performed in the course of and after preoperative chemotherapy to verify tumor response. Radiological staging plays a significant role in deciding on further treatment and in operative planning. Three-dimensional visualization of the abdominal situs can assist preoperative planning. In summary, diagnostic imaging in renal tumors in children plays a role in differential diagnosis, staging, monitoring of therapy, and surgical planning. |
| Scheiderbauer J, Gnekow AK, Emser A, Hildebrandt G, Bamberg M, Kortmann RD |
Multizentrische prospektive kooperative Studie SIOP/GPOH „Low grade glioma„ im Kindesalter von 1996: Ergebnisse nach Strahlentherapie (Deutschland). [+] |
Strahlenther Onkol 2005, 181 (Sondernr 1): 39 |
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| |
| Schrappe M, Creutzig U |
Akute lymphoblastische (ALL) und akute myeloische (AML) Leukämie im Kindesalter. Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie. |
AWMF online 2005 |
|
| Schmidt, RF |
Physiologie des Menschen. |
Springer Verlag 29., vollst. neu bearb. und aktualisierte Aufl., 2005 |
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| Schuck A, Ahrens S, von Schorlemer I, Kuhlen M, Paulussen M, Hunold A, Gosheger G, Winkelmann W, Dunst J, Willich N, Jürgens H |
Radiotherapy in Ewing tumors of the vertebrae: treatment results and local relapse analysis of the CESS 81/86 and EICESS 92 trials. [+] |
International journal of radiation oncology, biology, physics 2005, 63: 1562 |
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| PURPOSE: Treatment results in patients with Ewing tumors of the vertebrae enrolled in the Cooperative Ewing's Sarcoma Study (CESS) 81, 86, and the European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) 92 trials were analyzed with special emphasis on radiation-associated factors. PATIENTS AND METHODS: A retrospective analysis was performed on 116 patients with primary tumors of the cervical, thoracic, or lumbar vertebrae treated between 1981 and 1999. Furthermore, a relapse analysis was done on those patients who underwent radiotherapy and subsequently had a local recurrence. RESULTS: A total of 64.6% of the patients received definitive radiotherapy; 27.5% of patients had surgery and radiotherapy. Only 4 patients (3.4%) underwent definitive surgery. Twenty-seven patients presented with metastases at diagnosis. 22.4% of the total group developed a local relapse. Among the subgroup with definitive radiotherapy, local recurrence was seen in 17 of 75 patients (22.6%). Event-free survival and survival at 5 years were 47% and 58%, respectively. Of the 14 evaluable patients with a local relapse after radiotherapy, 13 were in-field. No correlation between radiation dose and local control could be found. CONCLUSION: Surgery with wide resection margins is rarely possible. The results after definitive radiotherapy in vertebral tumors are comparable to those of other tumor sites when definitive radiotherapy is given. Nearly all local relapses after radiotherapy are in-field. |
| Schuck A, Hamelmann V, Bramswig JH, Konemann S, Rube C, Hesselmann S, Riesenbeck D, Horst E, Bolling T, Paulussen M, Jürgens H, Willich N |
Ovarian function following pelvic irradiation in prepubertal and pubertal girls and young adult women. [+] |
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 2005, 181: 534 |
|
| PURPOSE: To analyze the effect of pelvic radiotherapy on ovarian function in prepubertal and pubertal girls and young adult women. PATIENTS AND METHODS: In a retrospective monoinstitutional analysis, patients < 30 years of age at diagnosis were included who had been irradiated between 1979 and 1998. The main tumor types were Hodgkin's disease (38%), Ewing's sarcoma (20%) and nephroblastoma (11%). Patients were classified into three groups according to the position of the ovary in relation to the radiation portals. Group 1 was defined by direct irradiation of both ovaries. Group 2 patients were included with both ovaries potentially located in the radiation portals. In group 3, at least one ovary was not directly irradiated. The median follow-up was 128 months. RESULTS: 16 of 55 analyzed patients were categorized in group 1. In ten of these patients, hormone status was evaluable. The ovarian doses were >/= 15 Gy. Except for one patient treated with 15 Gy all developed hormone failure. Eight of 14 patients of group 2 were evaluable. Seven of these patients developed ovarian failure. 19 of 24 patients in group 3 were evaluable. Nine of these patients developed ovarian failure. The observed difference in the rate of ovarian failure between the groups is statistically significant (p = 0.045). CONCLUSION: All patients receiving > 15 Gy to the ovaries developed hormone failure. In one case of a patient receiving an ovarian dose of 15 Gy, hormone failure was not found. In case of pelvic irradiation excluding at least one ovary, approximately half of the patients developed ovarian dysfunction, probably also due to the effects of polychemotherapy. |
| Schellong G, Dörffel W, Claviez A, Körholz D, Mann G, Scheel-Walter HG, Bokkerink JP, Riepenhausen M, Luders H, Potter R, Ruhl U, DAL/GPOH |
Salvage therapy of progressive and recurrent Hodgkin's disease: results from a multicenter study of the pediatric DAL/GPOH-HD study group. [+] |
Journal of clinical oncology 2005, 23: 6181 |
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| PURPOSE: To evaluate a salvage therapy (ST-HD-86) for patients with progressive and relapsed Hodgkin's disease after primary treatment in the pediatric DAL/GPOH studies. The essential chemotherapeutic regimens were ifosfamide, etoposide, and prednisone (IEP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). METHODS: One hundred seventy-six patients with progression (n = 51) or first relapse (n = 125) were enrolled by 67 centers. The median time from initial diagnosis to progression/relapse was 1.1 year (range, 0.1 to 15.3 years), and the patients' median age was 14.7 years (range, 4.3 to 24.5 years). Salvage chemotherapy consisted of two to three cycles of IEP alternating with one to two cycles of ABVD supplemented in part by one to two cycles of cyclophosphamide, vincristine, procarbazine, and prednisone or lomustine (CCNU), etoposide, and prednimustine. Radiotherapy was given to involved areas using individualized doses. In the 1990s, additional high-dose chemotherapy with autologous stem-cell transplantation (SCT) was introduced for patients with unfavorable prognosis. RESULTS: Disease-free survival (DFS) and overall survival (OS) after 10 years are 62% and 75%, respectively (SE, 4% each). Of 176 patients, 73 suffered second events. The risk-factor analysis revealed the time to progression/relapse as the strongest prognostic factor (P = .0001). Patients with progression have an inferior outcome (DFS, 41%; OS, 51%), whereas patients with late relapse (> 12 months after end of therapy) do well (DFS, 86%; OS, 90%), although none of them received SCT in second remission. CONCLUSION: The result can be considered favorable. Whereas the salvage strategy for progressive disease has to be optimized further, it is possible to reduce intensity and avoid SCT in late relapses after Hodgkin's disease in childhood/adolescence. |
| Schneider DT, Calaminus G, Harms D, Göbel U, German Maligne Keimzelltumoren Study Group |
Ovarian sex cord-stromal tumors in children and adolescents. [+] |
The Journal of reproductive medicine 2005, 50: 439 |
|
| Ovarian sex cord-stromal tumors (OSCSTs) are a heterogeneous group of tumors that develop from the gonadal non-germ-cell component. Despite recent advances in the clinical and histopathologic diagnosis of OSCSTs, a high degree of uncertainty remains with regard to adequate therapy, particularly in patients presenting with microscopic or macroscopic tumor spread. We review the currently available data on the biology and histology of OSCST in children and adolescents. In addition, we summarize the data from our clinical, histopathologic and genetic analyses of patients that were prospectively reported to the German MAKEI protocols for treatment of nontesticular malignant germ cell tumors. Among these patients, juvenile granulosa cell tumors (JGCTs) constitute the most frequent histologic subtype, followed by Sertoli-Leydig cell tumors (SLCTs) and sclerosing stromal tumors. Patients with JGCT and SLCT show greater mitotic activity than do all those with other histologic types. Furthermore, high mitotic activity is associated with adverse outcome. In addition, prognosis correlates with tumor stage according to the International Federation of Obstetrics and Gynecology. Nevertheless, we observed a favorable response to cisplatin-based chemotherapy in the majority of stage II and III tumors. For the whole cohort of 62 patients, event-free survival was 0.87 +/- 0.05 months and overall survival 0.88 +/- 0.05. Genetic analysis of 27 tumors available for comparative genomic hybridization analysis revealed normal profiles in the majority of tumors and whole chromosomal gain, such as a gain of 12 in single tumors, with no consistent pattern with regard to histology or clinical outcome. This analysis confirmed that most OSCSTs present at a low tumor stage and that prognosis in these patients is excellent. Most important, patients at high risk can be identified through clinical and histopathologic analysis, and the majority can be treated successfully with adjuvant cisplatinum-based chemotherapy. Based on this analysis, a prospective study on OSCST in children and adolescents began recruiting cases in 2005. |
| Schuck A, Ranft A, Dirksen U, Dunst J, Jürgens H, Willich, N |
Radiotherapy in Ewing tumours: Significance of fractionation. |
Strahlentherapie und Onkologie 2006, 182; 67 |
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| Schrauder A, Reiter A, Gadner H, Niethammer D, Klingebiel T, Kremens B, Peters C, Ebell W, Zimmermann M, Niggli F, Ludwig WD, Riehm H, Welte K, Schrappe M |
Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. [+] |
Journal of clinical oncology 2006, 24: 5742 |
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| PURPOSE: The role of hematopoietic stem-cell transplantation (SCT) in first complete remission (CR1) for children with very high-risk (VHR) acute lymphoblastic leukemia (ALL) is still under critical discussion. PATIENTS AND METHODS: In the ALL-Berlin-Frankfurt-Münster (BFM) 90 and ALL-BFM 95 trials, 387 patients were eligible for SCT if there was a matched sibling donor (MSD). T-cell ALL (T-ALL) patients with poor in vivo response to initial treatment represented the largest homogeneous subgroup within VHR patients. RESULTS: Of 191 high-risk (HR) T-ALL patients, 179 patients (94%) achieved CR1. Twenty-three patients received an MSD-SCT. Furthermore, in trial ALL-BFM 95, eight matched unrelated donors (MUDs) and five mismatched family donors (MMFDs) were used. The median time to SCT was 5 months (range, 2.4 to 10.8 months) from diagnosis. The 5-year disease-free survival (DFS) was 67% +/- 8% for 36 patients who received an SCT in CR1 and 42% +/- 5% for the 120 patients treated with chemotherapy alone having an event-free survival time of at least the median time to transplantation (Mantel-Byar, P = .01). Overall survival (OS) rate for the SCT group was 67% +/- 8% at 5 years, whereas patients treated with chemotherapy alone had an OS rate of 47% +/- 5% at 5 years (Mantel-Byar, P = .01). Outcome of patients who received MSD-SCT versus MUD-/MMFD-SCT was comparable (DFS, 65% +/- 10% v 69% +/- 13%, respectively). However, relapses only occurred after MSD-SCT (eight of 23 patients), whereas treatment-related mortality only occurred after MUD-/MMFD-SCT (four of 13 patients). CONCLUSION: SCT in CR1 is superior to treatment with chemotherapy alone for childhood HR-T-ALL. |
| Schmidt M, Simon T, Hero B, Eschner W, Dietlein M, Sudbrock F, Bongartz R, Berthold F, Schicha H |
Is there a benefit of 131 I-MIBG therapy in the treatment of children with stage 4 neuroblastoma? A retrospective evaluation of The German Neuroblastoma Trial NB97 and implications for The German Neuroblastoma Trial NB2004. [+] |
Nuklearmedizin. Nuclear medicine 2006, 45: 145-51; quiz N39 |
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| AIM: (131)I-meta-iodobenzylguanidine ((131)I-MIBG) therapy has been used in neuroblastoma treatment for many years but its value in high intensive first line treatment protocols is not exactly known. PATIENTS, METHODS: Stage 4 neuroblastoma patients >1 year with (123)I-MIBG positive residual disease (primary tumour and/or metastasis) after complete induction chemotherapy according to the German neuroblastoma trial NB97 were retrospectively analyzed. RESULTS: One-hundred-eleven patients had (123)I-MIBG positive residual disease after complete induction chemotherapy. Forty patients received (131)I-MIBG therapy using a median activity of 0.44 GBq/kg body weight. By univariate analysis, patients who underwent (131)I-MIBG therapy had a better 3-year event free survival (3-y-EFS 46 +/- 8%) and 3-year overall survival (3-y-OS 58 +/- 9%) than 71 patients without (131)I-MIBG therapy (3-y-EFS 19 +/- 5%, p = 0.003; 3-y-OS 43 +/- 6%, p = 0.037). However, subgroup analysis of 66 patients who underwent high dose chemotherapy with autologous stem cell transplantation (ASCT) during treatment found a very similar outcome with (131)I-MIBG therapy (3-y-EFS 49 +/- 9%, 3-y-OS 59 +/- 10%) and without (131)I-MIBG therapy (3-y-EFS 33 +/- 9%, p = 0.171; 3-y-OS 59 +/- 9%, p = 0.285) due to the dominating effect of ASCT. By multivariate analysis, (131)I-MIBG therapy had no impact on EFS (p = 0.494) and OS (p = 0.891). Only ASCT, external beam radiation therapy and MYCN amplification were important for EFS and OS. CONCLUSIONS: An independent advantage of I-131-MIBG therapy could not be proven in this retrospective analysis. The ongoing German Neuroblastoma Trial NB2004 will address the influence of (131)I-MIBG therapy with emphasis on tumour dosimetry. |
| Schneider DT, Zahn S, Sievers S, Alemazkour K, Reifenberger G, Wiestler OD, Calaminus G, Göbel U, Perlman EJ |
Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization. [+] |
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2006, 19: 864 |
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| The limited information available to date regarding the genetic alterations in germ cell tumors of the central nervous system has raised concerns about their biologic relationship to other germ cell tumor entities. We investigated fresh-frozen or archival tumor samples from 19 patients with central nervous system germ cell tumors (CNS-GCTs), including seven germinomas, eight malignant nongerminomatous germ cell tumors and four teratomas, using chromosomal comparative genomic hybridization to determine recurrent chromosomal imbalances. All 15 malignant CNS-GCTs and two of four teratomas showed multiple chromosomal imbalances. Chromosomal gains (median: 4 gains/tumor, range: 0-9 gains/tumor) were observed more frequently than losses (median: 1.6 losses/tumor, range: 0-6 losses/tumor). Gain of 12p, which is considered characteristic for germ cell tumors of the adult testis, was detected in 11 of 19 tumors and 10 of 15 malignant CNS-GCTs. In one tumor, gain of 12p was confined to an amplicon at 12p12, corresponding to the commonly amplified region on 12p. Other common gains were found on chromosome arms 1q and 8q (n = 9, each). Among the chromosomal losses, parts of chromosome 11 (n = 5), 18 (n = 4), and 13 (n = 3) were deleted most frequently. Notably, we observed no difference in the genetic profiles of germinomatous and nongerminomatous CNS-GCTs; however, the average number of imbalances was higher in the latter group. A meta-analysis comparing 116 malignant gonadal and extragonadal germ cell tumors revealed that the genomic alterations in CNS-GCTs are virtually indistinguishable from those found in their gonadal or other extragonadal counterparts of the corresponding age group. These data strongly argue in favor of common pathogenetic mechanisms in gonadal and extragonadal germ cell tumors. |
| Schrappe M, Harbott J, Riehm H |
Akute lymphoblastische Leukämien. |
In: Gadner H, Gaedicke G, Niemeyer C, Ritter J, editors. Pädiatrische Hämatologie und Onkologie Berlin, Heidelberg, New York: Springer Verlag, 2006, 656-679. |
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| Schwartz S, Borner K, Müller K, Martus P, Fischer L, Korfel A, Auton T, Thiel E |
Glucarpidase (carboxypeptidase g2) intervention in adult and elderly cancer patients with renal dysfunction and delayed methotrexate elimination after high-dose methotrexate therapy. [+] |
Oncologist 2007, 12: 1299 |
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| Leucovorin and extracorporeal removal of methotrexate (MTX) have limited efficacy in delayed MTX elimination after high-dose methotrexate (HD-MTX) therapy. Glucarpidase (carboxypeptidase G2) cleaves MTX into nontoxic metabolites, but experience with this enzyme is limited in adult patients. We evaluated the effects of glucarpidase intervention in adult and elderly patients with delayed MTX elimination. |
| Schüz J, Weihkopf T, Kaatsch P |
Medication use during pregnancy and the risk of childhood cancer in the offspring. [+] |
European journal of pediatrics 2007, 166: 433 |
|
| The young age at onset of many cancers in childhood has led to investigations on maternal exposures during pregnancy. Data from a population-based case-control study in Germany (1992-1997) that included 1,867 cases and 2,057 controls was used to investigate this question. Maternal use of vitamin, folate or iron supplementation was associated with a reduced risk of non-Hodgkin lymphoma and tumors and, less clearly, with leukemia, but not with CNS tumors. An increased risk of neuroblastoma was associated most markedly with diuretics and other antihypertensives, but also with vitamin, folate or iron supplementation. No associations were seen with pain relievers, antinauseants or cold medications, nor with delivery by Caesarian section. The strengths of this study are its population base, the large number of cases and the inclusion of different case groups to identify disease specificity of associations. The limitation of this study is an exposure assessment relying on maternal self-reports. In conclusion, these data indicate a potential influence of some maternal medication during pregnancy on the risk of childhood cancer in the offspring; however, no clear picture is seen. |
| Schaefer KL, Eisenacher M, Braun Y, Brachwitz K, Wai DH, Dirksen U, Lanvers-Kaminsky C, Jürgens H, Herrero D, Stegmaier S, Koscielniak E, Eggert A, Nathrath M, Gosheger G, Schneider DT, Bury C, Diallo-Danebrock R, Ottaviano L, Gabbert HE, Poremba C |
Microarray analysis of Ewing's sarcoma family of tumours reveals characteristic gene expression signatures associated with metastasis and resistance to chemotherapy. [+] |
European journal of cancer (Oxford, England : 1990) 2008, 44: 699 |
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| In Ewing's sarcoma family of tumours (ESFT), the clinically most adverse prognostic parameters are the presence of tumour metastasis at time of diagnosis and poor response to neoadjuvant chemotherapy. To identify genes differentially regulated between metastatic and localised tumours, we analysed 27 ESFT specimens using Affymetrix microarrays. Functional annotation of differentially regulated genes revealed 29 over-represented pathways including PDGF, TP53, NOTCH, and WNT1-signalling. Regression of primary tumours (n=20) induced by polychemotherapy was found to be correlated with the expression of genes involved in angiogenesis, apoptosis, ubiquitin proteasome pathway, and PI3 kinase and p53 pathways. These findings could be confirmed by in vitro cytotoxicity assays. A set of 46 marker genes correctly classifies these 20 tumours as responding versus non-responding. We conclude that expression signatures of initial tumour biopsies can help to identify ESFT patients at high risk to develop tumour metastasis or to suffer from a therapy refractory cancer. |
| Schrappe M, Creutzig U |
Akute lymphoblastische (ALL) und akute myeloische (AML) Leukämie im Kindesalter. Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie. |
AWMF online 2008 |
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| Schrauder A, von Stackelberg A, Schrappe M, Cornish J, Peters C, ALL-BFM Study Group, EBMT PD WP, I-BFM Study Group |
Allogeneic hematopoietic SCT in children with ALL: current concepts of ongoing prospective SCT trials. [+] |
Bone marrow transplantation 2008, 41 Suppl 2:S71 |
|
| The definition of indications for allogeneic SCT in children with high-risk (HR) ALL in the first remission or after the first or subsequent relapse depends on biological features, response to treatment and survival after chemotherapy alone. As the results of frontline and relapse protocols are improving over time, there is a strong need for prospective SCT trials, ensuring a well-standardized procedure regarding all relevant components that are potentially responsible for heterogeneity in post-SCT outcome. Therefore, in 2003, the ALL-BFM and the ALL-REZ BFM Study Group initiated a prospective, international, multicenter trial (ALL-SCT-BFM 2003). This trial will now be extended to a larger consortium, trial ALL-SCT-BFM-international (ALL-SCT-BFMi). Strict rules define HLA-typing, donor selection, conditioning regimen, GvHD prophylaxis and therapy as well as standards of supportive care to reduce treatment-related mortality and establish an early GVL effect. Moreover, comprehensive and closely reviewed documentation and serious adverse event reporting shall ensure high study quality. Case-by-case discussions of any fatal or critical course during annual meetings will improve the culture of failure management and lead to modifications of guidelines of supportive care. Finally, the results of these prospective trials will determine the current potential of the different SCT procedures in HR or relapsed childhood ALL. |
| Schmidt M, Simon T, Hero B, Schicha H, Berthold F |
The prognostic impact of functional imaging with (123)I-mIBG in patients with stage 4 neuroblastoma >1 year of age on a high-risk treatment protocol: results of the German Neuroblastoma Trial NB97. [+] |
European journal of cancer (Oxford, England : 1990) 2008, 44: 1552 |
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| AIM/PURPOSE: (123)I-meta-iodobenzylguanidine ((123)I-mIBG) scintigraphy is well established for staging and evaluation of response in children with high-risk neuroblastoma but its prognostic value in highly intensive first-line treatment protocols is uncertain. The presence of any (123)I-mIBG positive tumour tissue was correlated with event-free survival (EFS) and overall survival (OS). PATIENTS AND METHODS: The prognostic impact of residual (123)I-mIBG uptake into the primary tumour and metastases for predicting outcome in 113 stage 4 neuroblastoma patients >1 year of the German Neuroblastoma Trial NB97 was assessed using a univariate log-rank test and multivariate Cox regression analysis. RESULTS: All patients had (123)I-mIBG positive disease at initial staging. After four courses of induction chemotherapy, 71% of patients were still (123)I-mIBG positive for the primary tumour and 61% for metastases. After six courses, 39% of patients had (123)I-mIBG uptake by the primary tumour and 45% residual (123)I-mIBG positive metastatic disease. The (123)I-mIBG status of the primary tumour site had no bearing on outcome. Residual (123)I-mIBG positive metastatic disease after four (3-y-EFS 25.7+/-5.3% versus 55.9+/-7.6%, p=0.009; 3-y-OS 49.8+/-6.1% versus 65.0+/-7.3%; p=0.021) and after six chemotherapy cycles (3-y-EFS 27.5+/-6.2% versus 47.4+/-6.4%, p=0.011; 3-y-OS 50.5+/-7.1% vs 60.0+/-6.4%, p=0.031) was associated with poor outcome. CONCLUSION: Functional imaging with (123)I-mIBG scintigraphy can identify poor responders with any persistent metastatic (123)I-mIBG uptake who are at a high risk of disease relapse. (123)I-mIBG response of the primary tumour site had no bearing on outcome. |
| Schrappe M |
Risk-adapted stratification and treatment of childhood acute lymphoblastic leukaemia. [+] |
Radiation protection dosimetry 2008, 132: 130 |
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| Systematic enrollment of children and adolescents with acute lymphoblastic leukaemia (ALL) into clinical trials has allowed the establishment of prognostic parameters derived from initial diagnostic findings. More important, these trials have significantly contributed to the reduction of disease recurrence as much as to the reduction of acute and late side effects. Some problems that are related to the specificity of the parameters used for risk assessment were not overcome: high tumour load by white blood cell count (WBC), age and (rare) cytogenetic subtypes (e.g. t9;22) may characterise a significant proportion of children and adolescents with high-risk ALL. Most patients who will eventually relapse do not present with characteristic features at initial diagnosis. It appears feasible through careful response assessment to identify these patients at risk of relapse, who present initially without specific features. Earlier trials of the ALL-BFM (Berlin/Frankfurt/Münster) study group and others have demonstrated that inadequate leukaemic blast reduction in the peripheral blood or bone marrow after the first few days of therapy is highly predictive of treatment failure. Using clone-specific polymerase chain reaction-based detection of minimal residual disease (MRD) as done in trial AIEOP-BFM ALL 2000 allowed a close surveillance of specific treatment elements when applied in MRD positive patients. This may facilitate innovative chemotherapy approaches and a more rational use of allogeneic haematopoetic stem cell transplantation. In addition, genetic signatures of treatment response or failure have been identified. |
| Schmid H, Jaeger B, Lohse J, Suttorp M |
Longitudinal growth retardation in a prepuberal girl with chronic myeloid leukemia on long-term treatment with imatinib. |
Haematologica 2009, 94: 1177 |
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| Schwarz AK, Stanulla M, Cario G, Flohr T, Sutton R, Möricke A, Anker P, Stroun M, Welte K, Bartram CR, Schrappe M, Schrauder A |
Quantification of free total plasma DNA and minimal residual disease detection in the plasma of children with acute lymphoblastic leukemia. [+] |
Annals of hematology 2009, 88: 897 |
|
| The analysis of total plasma DNA and the monitoring of leukemic clone-specific immunoglobulin and/or T-cell receptor gene rearrangements for the evaluation of minimal residual disease (MRD) in the plasma may be useful tools for prognostic purposes or for early detection of subclinical disease recurrence in children with acute lymphoblastic leukemia (ALL). The aim of this paper is to establish reference ranges for total plasma DNA concentrations and to test the feasibility of MRD measurements employing plasma DNA from children with ALL by using real-time quantitative (RQ)-PCR. Despite wide inter-individual variation, the median concentrations of total plasma DNA for 12 healthy donors (57 ng/ml), 21 children with ALL after day 4 of treatment initiation (62 ng/ml) and 13 children with other malignancies (76 ng/ml) were similar. However, ALL patients had significantly higher concentrations at diagnosis (277 ng/ml) and on treatment day 3 (248 ng/ml) before returning to normal afterwards. Early plasma DNA MRD kinetics could be established for 15 ALL patients and showed good concordance with bone marrow MRD. Plasma DNA was higher in children with ALL at diagnosis but returned to normal within the first four treatment days. Despite low concentrations of DNA, it is feasible to measure MRD kinetics in plasma DNA during ALL induction therapy by adapted real-time PCR methodologies. |
| von Schweinitz, D |
Tumoren der Leber, des Pankreas und des Gastrointestinaltraktes. [+] |
Kinderchirurgie |
|
| Primäre Tumoren der Leber, des Pankreas oder des Gastrointestinaltraktes kommen im Kindesalter sehr selten vor. Dabei kann man in allen drei Organen auf eine große Variabilität der Entitäten stoßen, von denen die Mehrzahl maligne ist. Säuglinge und junge Kinder erkranken außer an gutartigen Tumoren der Leber und des Pankreas vor allem an embryonalen malignen Tumoren dieser Organe, dem Hepatoblastom und dem Pankreatoblastom. Diese zeigen ein gutes Ansprechen auf Chemotherapie. Therapeutisch steht bei den benignen Tumoren, wie auch bei den übrigen malignen Neoplasien der Leber (hepatozelluläres Karzinom, Sarkome), des Pankreas (Pankreaskarzinom) und des Magen-Darm-Traktes (Karzinome) die komplette chirurgische Resektion im Vordergrund. Wie beim Erwachsenen wirken Chemotherapie und Bestrahlung bei den Karzinomen auch des Kindesalters nur schlecht. Während Kinder und Jugendliche mit benignen Tumoren eine gute, solche mit embryonalen malignen Tumoren eine mäßige Überlebenschance haben, ist diese bei Karzinompatienten in der Regel sehr schlecht. |
| Schwarz K, Iolascon A, Verissimo F, Trede NS, Horsley W, Chen W, Paw BH, Hopfner KP, Holzmann K, Russo R, Esposito MR, Spano D, De Falco L, Heinrich K, Joggerst B, Rojewski MT, Perrotta S, Denecke J, Pannicke U, Delaunay J, Pepperkok R, Heimpel H |
Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II. [+] |
Nature genetics 2009, 41: 936 |
|
| Congenital dyserythropoietic anemias (CDAs) are phenotypically and genotypically heterogeneous diseases. CDA type II (CDAII) is the most frequent CDA. It is characterized by ineffective erythropoiesis and by the presence of bi- and multinucleated erythroblasts in bone marrow, with nuclei of equal size and DNA content, suggesting a cytokinesis disturbance. Other features of the peripheral red blood cells are protein and lipid dysglycosylation and endoplasmic reticulum double-membrane remnants. Development of other hematopoietic lineages is normal. Individuals with CDAII show progressive splenomegaly, gallstones and iron overload potentially with liver cirrhosis or cardiac failure. Here we show that the gene encoding the secretory COPII component SEC23B is mutated in CDAII. Short hairpin RNA (shRNA)-mediated suppression of SEC23B expression recapitulates the cytokinesis defect. Knockdown of zebrafish sec23b also leads to aberrant erythrocyte development. Our results provide in vivo evidence for SEC23B selectivity in erythroid differentiation and show that SEC23A and SEC23B, although highly related paralogous secretory COPII components, are nonredundant in erythrocyte maturation. |
| Schrappe M, Nachman J, Hunger S, Schmiegelow K, Conter V, Masera G, Pieters R, Pui CH |
'Educational symposium on long-term results of large prospective clinical trials for childhood acute lymphoblastic leukemia (1985-2000)'. |
Leukemia 2010, 24: 253 |
|
| Schrey D, Borghorst S, Lanvers-Kaminsky C, Hempel G, Gerss J, Möricke A, Schrappe M, Boos J |
Therapeutic drug monitoring of asparaginase in the ALL-BFM 2000 protocol between 2000 and 2007. [+] |
Pediatric blood & cancer 2010, 54: 952 |
|
| BACKGROUND: On a voluntary basis therapeutic drug monitoring (TDM) was implemented in the ALL-BFM 2000 protocol for the three currently used asparaginase (ASNase) preparations (first line: native Escherichia coli ASNase; second line: pegylated ASNase and third line: Erwinia chrysanthemi ASNase). PROCEDURE: Between 2000 and 2007, 2,074 ASNase samples from 763 patients out of 114 hospitals were evaluated (5,000 U/m2 E. coli ASNase (n = 318), 1,000 U/m2 pegylated ASNase (n = 416) and 10,000 U/m2 Erwinia chrysanthemi ASNase (n = 29)). RESULTS: First-line therapy with 5,000 U/m2 E. coli ASNase resulted in an ASNase activity of <100 U/L in 10% of all samples from day +3 after administration. Second-line treatment with 1,000 U/m2 PEG ASNase led to activity values below 100 U/L in approximately 30% of all samples taken +7 days. Relating ASNase activity to route of administration, 10,000 U/m2 Erwinia ASNase IM compared to IV as third-line treatment, led to a higher median activity (IM: median 151.5 U/L, range (0-750 U/L); IV: median 115 U/L, range (0-884 U/L), P = 0.3) and fewer samples below 100 U/L (IM: 15% vs. IV: 45%) at day +2. CONCLUSION: The reduced dose of 5,000 U/m2 E. coli ASNase for induction treatment succeeded to achieve an activity level above 100 U/L in more than 90% of all samples. They confirm that dose reduction is reasonable and provide the basis for future treatment strategies employing ASNase. |
| Schwarz R, Bruland O, Cassoni A, Schomberg P, Bielack S |
The role of radiotherapy in oseosarcoma. [+] |
Cancer treatment and research 2010, 152: 147 |
|
| A survey of the literature shows that the experience with radiotherapy (RT) in the local treatment of osteosarcoma (OS) is limited. This is due to various reasons: OS is a rare tumor and surgery is the treatment of choice with high local control rate, and uncertainty exists in regard to the efficacy and tolerance of radiotherapy. Publications on this topic were analyzed and will be reviewed. Furthermore, experience from the Cooperative Osteosarkomstudiengruppe (COSS)-Registry, including 100 patients (pts) treated using radiotherapy for OS, was analyzed.The COSS-registry includes a total of 175 pts (5% of all pts) with histologically proven OS irradiated over the period of 1980-2007. 100 pts were eligible for analysis. The median age was 18 (3-66) years. Indication for RT was a primary tumor in 66, a local recurrence in 11, and metastases in 23 pts. 94 pts got external photontherapy; 2 pts, proton therapy; 2 pts, neutron therapy; and 2 pts, intraoperative RT. In addition, a group of 17 pts received bone-targeted radionuclide therapy by samarium-153-EDTMP-therapy alone or in combination with external RT. The median dose for external RT was 55.8 Gy (30-120). All the pts received chemotherapy in accordance with different COSS-protocols.The median follow-up was 1.5 (0.2-23) years. Survival and local control rates at 5 years were calculated, and univariate and multivariate analyses performed. 41 pts are alive, 59 pts died. The overall survival rate after biopsy was 41% at 5 years, while the overall survival rates after RT for the whole group, for treatment of primary tumors, local recurrence, and metastases were 36%, 55%, 15%, and 0% respectively.In 41 cases, local control was achieved, whereas local progression or local recurrence occurred in 59 cases, with a median time to local recurrence of 0.5 (0.1-4) years after RT. 15 pts were nonresponders to radiotherapy. Local control for the whole group was 30%. Local control rates for combined surgery and RT were significantly better than those for RT alone (48% vs. 22%, p=0.002). Local control for treatment of primary tumors, local recurrence, and metastases were 40%, 17%, and 0% respectively. Local control for pts given an addition of samarium-153-EDTMP was poor, though not statistically significant . A dose of over 60 Gy had no significant effect on local control. Prognostic factors for survival were indication for RT, RT plus surgery vs. RT alone and tumor location. Prognostic factors for local control were indication for RT, and RT plus surgery vs. RT alone.For the majority of pts, surgery remains the local treatment of choice. Radiotherapy is an important option as local treatment of unresectable tumors, following intralesional resection, or as palliation of symptomatic metastases. Survival prognosis of such pts, however, is poor. Despite the fact that many of these pts will eventually die, they may benefit in terms of prolonged survival and prolonged local control. The combination of surgery, radiotherapy, and chemotherapy can be curative. The consistent use of full-dose chemotherapy is of importance for the response to radiotherapy. Prognostic factors for survival are indication for RT, RT plus surgery vs. RT alone and tumor location. Prognostic factors for local control are indication for RT, and RT plus surgery vs. RT alone. |
| Schneppenheim R, Frühwald MC, Gesk S, Hasselblatt M, Jeibmann A, Kordes U, Kreuz M, Leuschner I, Martin Subero JI, Obser T, Oyen F, Vater I, Siebert R |
Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family with rhabdoid tumor predisposition syndrome. [+] |
American journal of human genetics 2010, 86: 279 |
|
| Rhabdoid tumors of early infancy are highly aggressive with consequent poor prognosis. Most cases show inactivation of the SMARCB1 (also known as INI1 and hSNF5) tumor suppressor, a core member of the ATP-dependent SWI/SNF chromatin-remodeling complex. Familial cases, described as rhabdoid tumor predisposition syndrome (RTPS), have been linked to heterozygous SMARCB1 germline mutations. We identified inactivation of another member of the SWI/SNF chromatin-remodeling complex, its ATPase subunit SMARCA4 (also known as BRG1), due to a SMARCA4/BRG1 germline mutation and loss of heterozygosity by uniparental disomy in the tumor cells of two sisters with rhabdoid tumors lacking SMARCB1 mutations. SMARCA4 is thus a second member of the SWI/SNF complex involved in cancer predisposition. Its general involvement in other tumor entities remains to be established. |
| Schellong G, Riepenhausen M, Bruch C, Kotthoff S, Vogt J, Bölling T, Dieckmann K, Pötter R, Heinecke A, Brämswig J, Dörffel W |
Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for hodgkin disease in children and adolescents: Report from the longitudinal GPOH follow-up project of the German-Austrian DAL-HD studies. [+] |
Pediatric blood & cancer 2010, 55: 1145-52. |
|
| BACKGROUND: To analyze the impact of mediastinal irradiation on the incidence of cardiac late effects in long-term survivors of pediatric Hodgkin disease (HD). METHODS: The study cohort comprised 1,132 survivors of HD who received treatment before 18 years of age in consecutive trials between 1978 and 1995. They had maintained remission without secondary malignancy for 3.1-29.4 years. The cumulative doxorubicin dose was uniformly 160 mg/m(2), the mediastinal radiation dose (MedRD) was 36, 30, 25, 20, or 0 Gy. Follow-up questionnaires complemented by additional contacts served to collect information on late effects from patients and physicians. A central expert panel reviewed all reported cardiac abnormalities. RESULTS: By October 2008, cardiac diseases (CD) had been diagnosed in 50 of 1,132 patients aged 15.0-41.7 (median 32.2) years. The interval since HD therapy was 3.0-28.2 (median 19.5) years. Valvular defects were diagnosed most frequently, followed by coronary artery diseases, cardiomyopathies, conduction disorders, and pericardial abnormalities. The cumulative incidence of CD after 25 years was highest in the MedRD-36 group (21%) decreasing to 10%, 6%, 5%, and 3% in the lower MedRD groups (P < 0.001). Multivariate Cox analysis of several putative risk factors showed MedRD to be the only significant variable predicting for CD-free survival (P = 0.0025). CONCLUSIONS: Our results indicate that lower MedRDs are less cardiotoxic. Consequently, reduction of cardiac late effects may be expected with the lower radiation doses used in current HD protocols. Longer follow-up is needed to confirm the present results. Pediatr Blood Cancer. (c) 2010 Wiley-Liss, Inc. |
| Schneider DT, Brecht IB |
Care for rare cancers: improved care requires improved communication. |
Klinische Padiatrie 2010, 222: 124 |
|
| Schneider DT, Brecht I |
Ein Netzwerk für besonders seltene Tumoren. |
WIR 2010, 3/10, 18 |
|
| von Schweinitz D |
Hepatoblastom. |
Leitlinie der Gesellschäft für Pädiatrische Onkologie und Hämatologie AWMF online 2010 |
|
| Schmid S |
Der Zahlen-GAU. |
Neue Zürcher Zeitung am Sonntag Online 20.03.2011 |
|
| Schmitz M, Breithaupt P, Scheidegger N, Cario G, Bonapace L, Meissner B, Mirkowska P, Tchinda J, Niggli FK, Stanulla M, Schrappe M, Schrauder A, Bornhauser BC, Bourquin JP |
Xenografts of highly resistant leukemia recapitulate the clonal composition of the leukemogenic compartment. [+] |
Blood 2011,Epub ahead of print |
|
| Clonal evolution of the leukemogenic compartment may contribute to alter the therapeutic response in acute lymphoblastic leukemia (ALL). Using xenotransplantation of primary leukemia cells we evaluated the phenotypic and genetic composition of de novo resistant very high risk (VHR) precursor B-cell ALL, a subgroup defined by the persistence of minimal residual disease (MRD) despite intensive chemotherapy. Analysis of copy number alterations (CNA) showed that the xenografted leukemia, even when reconstituted from hundred cells, remained highly related to the diagnostic sample, with minor changes in CNAs, mostly deletions, emerging in most cases in the first passage into mice. At the single cell level, the pattern of mono-and bi-allelic deletions of the CDKN2A locus revealed distinct leukemia subpopulations, which were reproducibly tracked in xenografts. In most VHR-ALL cases, the predominant diagnostic clones were reconstituted in xenografts, as shown by multiplex PCR analysis of Ig/TCR loci. In other cases, the pattern in CNAs and Ig/TCR rearrangement was less concordant in xenografts, suggesting the outgrowth of subclones. These results unequivocally demonstrate the existence of clonally closely related but distinct subsets of leukemia initiating cells in ALL, which has important implications for drug development and preclinical disease modeling. |
| Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grümayer R, Möricke A, Parasole R, Zimmermann M, Dworzak M, Buldini B, Reiter A, Basso G, Klingebiel T, Messina C, Ratei R, Cazzaniga G, Koehler R, Locatelli F, Schäfer BW, Aricò M, Welte K, van Dongen JJ, Gadner H, Biondi A, Conter V |
Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. [+] |
Blood 2011, 118: 2077 |
|
| The prognostic value of MRD in large series of childhood T-ALL has not yet been established. Trial AIEOP-BFM-ALL 2000 introduced standardized quantitative assessment of MRD for stratification, based on immunoglobulin and TCR gene rearrangements as polymerase chain reaction targets: Patients were considered MRD standard risk (MRD-SR) if MRD was negative at day 33 (time point 1 [TP1]) and day 78 (TP2), analyzed by at least 2 sensitive markers; MRD intermediate risk (MRD-IR) if positive either at day 33 or 78 and < 10(-3) at day 78; and MRD high risk (MRD-HR) if ≥ 10(-3) at day 78. A total of 464 patients with T-ALL were stratified by MRD: 16% of them were MRD-SR, 63% MRD-IR, and 21% MRD-HR. Their 7-year event-free-survival (SE) was 91.1% (3.5%), 80.6% (2.3%), and 49.8% (5.1%) (P < .001), respectively. Negativity of MRD at TP1 was the most favorable prognostic factor. An excellent outcome was also obtained in 32% of patients turning MRD negative only at TP2, indicating that early (TP1) MRD levels were irrelevant if MRD at TP2 was negative (48% of all patients). MRD ≥ 10(-3) at TP2 constitutes the most important predictive factor for relapse in childhood T-ALL. The study is registered at http://www.clinicaltrials.gov; |
| Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grümayer R, Möricke A, Parasole R, Zimmermann M, Dworzak M, Buldini B, Reiter A, Basso G, Klingebiel T, Messina C, Ratei R, Cazzaniga G, Köhler R, Locatelli F, Schäfer BW, Aricò M, Welte K, van Dongen JJ, Gadner H, Biondi A, Conter V |
Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. [+] |
Blood 2011, [Epub ahead of print] |
|
| The prognostic value of minimal residual disease (MRD) in large series of childhood T-ALL has not yet been established. Trial AIEOP-BFM-ALL 2000 introduced standardized quantitative assessment of MRD for stratification, based on immunoglobulin and T-cell receptor gene rearrangements as PCR targets: Patients were considered MRD standard risk (MRD-SR) if MRD was negative at day 33 (TP1) and day 78 (TP2), analyzed by at least two sensitive markers; MRD intermediate risk (MRD-IR) if positive either at day 33 or 78 and <10(-3) at day 78; MRD high risk (MRD-HR) if ≥10(-3) at day 78. 464 patients with T-ALL were stratified by MRD: 16% of them were MRD-SR, 63% MRD-IR and 21% MRD-HR. Their 7-year event-free-survival (SE) was 91.1% (3.5), 80.6% (2.3), and 49.8% (5.1) (p-value<0.001), respectively. Negativity of MRD at TP1 was the most favorable prognostic factor. An excellent outcome was also obtained in 32% of patients turning MRD negative only at TP2 indicating that early (TP1) MRD levels were irrelevant if MRD at TP2 was negative (48% of all patients). MRD ≥10(-3) at TP2 carried a significantly higher risk of relapse overall and in major subsets of T-ALL, thus, defining the most important predictive factor for relapse in childhood T-ALL. The study is registered at the US National Institutes of Health website http://clinicaltrials.gov as "Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia" with Protocol identification number NCT00430118 for BFM and NCT00613457 for AIEOP. |
| Schmid I, Häberle B, Albert MH, Corbacioglu S, Fröhlich B, Graf N, Kammer B, Kontny U, Leuschner I, Scheel-Walter HG, Scheurlen W, Werner S, Wiesel T, von Schweinitz D |
Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma. [+] |
Pediatric blood & cancer 2011, 58: 539 |
|
| PURPOSE: Overall survival is poor in children with primary unresectable hepatocellular carcinoma. Sorafenib has been shown to significantly improve progression-free survival in adult hepatocellular carcinoma (HCC) patients. We evaluated the experience of PLADO (cisplatin 80 mg/m(2) /day, doxorubicin 2 × 30 mg/m(2) /day) in combination with sorafenib in pediatric HCC patients. PATIENTS AND METHODS: Clinical data of 12 patients (7-16 years), 7 with unresectable tumor, were retrospectively assessed. RESULTS: In total 6/12 (50%) patients are in complete remission after a median follow-up of 20 months (4 with PLADO/sorafenib/resection, 2 with liver transplantation after local relapse). Of the seven patients with unresectable tumor, PLADO/sorafenib resulted in partial response (PR) in four, stable disease (SD) in two, and progression in one. Three are alive in CR after complete resection after 12 (alternative therapy after two cycles PLADO/sorafenib), 12 and 18 months (six cycles PLADO/sorafenib), respectively. All four patients with elevated alpha-fetoprotein levels had a marked drop after two cycles. Of the five patients with primary complete tumor resection one is alive disease-free at 27 months. Four had local or metastatic relapses (13, 7, 12, and 13 months), two of whom were rescued by liver transplantation (CR after 25 and 32 months). The main toxicity attributable to sorafenib was a hand-foot skin reaction (HFSR) in seven patients. CONCLUSION: Sorafenib in combination with PLADO may be a promising approach in pediatric HCC; HFSR was the most important toxicity. Data based on prospective studies are needed to evaluate pharmacokinetics, resectability rates, and survival in pediatric HCC treated with sorafenib. Pediatr Blood Cancer © 2011 Wiley-Liss, Inc. |
| Schneider DT, Brecht IB, Olson ThA, Ferrari A (Eds) |
Rare Tumors In Children and Adolescents. [+] |
Series: Pediatric Oncology 2012, ISBN 978-3-642-04196 |
|
| This is the first book to be devoted exclusively to rare tumors in children and adolescents, and its aim is to provide up-to-date information on their diagnosis and clinical management. |
| Schrappe M, Hunger SP, Pui CH, Saha V, Gaynon PS, Baruchel A, Conter V, Otten J, Ohara A, Versluys AB, Escherich G, Heyman M, Silverman LB, Horibe K, Mann G, Camitta BM, Harbott J, Riehm H, Richards S, Devidas M, Zimmermann M |
Outcomes after induction failure in childhood acute lymphoblastic leukemia. [+] |
N Engl J Med 2012, 366: 1371 |
|
| Failure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL). |
| von Schweinitz D |
Hepatoblastoma: recent developments in research and treatment. [+] |
Seminars in pediatric surgery 2012, 21: 21 |
|
| Hepatoblastoma is the most common liver tumor of early childhood. According to recent studies its incidence seems to be increasing in North America and Europe. Since new histological variants have been described recently the formerly clear-cut distinction of hepatoblastoma and hepatocellular carcinoma may not be valid anymore and a new histological classification will be inaugurated by an international working group. Recent research identified prognostically relevant gene signatures as well as potential molecular targets for therapy of hepatoblastoma. The multicentric study groups in the USA, Europe and Japan recommend cisplatin based chemotherapy for neoadjuvant and adjuvant treatment. However, their risk stratification systems and general treatment strategies differ substantially. Therefore the four groups agreed to pool their patients' data for an analysis of prognostic criteria which can be used for defining common risk groups. While 90% of standard risk and 65% of high risk hepatoblastomas can be cured, the still dismal outcome of multifocal disseminated and metastasising tumors warrants the investigation of new cytotoxic drugs and substances against specific molecular targets. |
| Schmid I, Häberle B, Albert MH, Corbacioglu S, Fröhlich B, Graf N, Kammer B, Kontny U, Leuschner I, Scheel-Walter HG, Scheurlen W, Werner S, Wiesel T, von Schweinitz D |
Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma. [+] |
Pediatric blood & cancer 2012, 58: 539 |
|
| Overall survival is poor in children with primary unresectable hepatocellular carcinoma. Sorafenib has been shown to significantly improve progression-free survival in adult hepatocellular carcinoma (HCC) patients. We evaluated the experience of PLADO (cisplatin 80 mg/m(2) /day, doxorubicin 2 × 30 mg/m(2) /day) in combination with sorafenib in pediatric HCC patients. |
| Schönberger S, Okpanyi V, Calaminus G, Heikaus S, Leuschner I, Nicholson JC, Stoecklein NH, Schneider DT, Borkhardt A |
EPCAM-A novel molecular target for the treatment of pediatric and adult germ cell tumors. [+] |
Genes, chromosomes & cancer 2013, 52: 24 |
|
| Germ cell tumors (GCTs) are thought to develop from totipotent primordial germ cells. Although the epithelial cell adhesion molecule (EPCAM) is expressed on embryonic stem cells as well as different tumor cells, it has not yet been extensively studied in GCTs. We analyzed EPCAM expression by quantitative RT-PCR in 48 fresh-frozen GCT specimens of different histology (10 mature teratoma, MT; 6 immature teratoma, IT; 7 dysgerminoma; 6 mixed malignant GCTs; 19 yolk sac tumor, YST) and in the GCT cell lines NCCIT, TE76.T, JAR and 2102Ep, and correlated its expression with AFP and hCG protein levels, histologic differentiation, and clinical follow-up data. EPCAM protein was visualized by immunohistochemistry of selected corresponding paraffin embedded tumor tissues. EPCAM was expressed in malignant but not in benign GCTs irrespective of age, sex, site and clinical stage of tumor (P = 0.001). In primary teratomas, EPCAM expression increased with their grade of immaturity (mean 2(-ΔCt) values: MT 0.23, IT 1.61, P = 0.007) and significantly correlated with serum AFP (P = 0.03) and hCG (P = 0.03) levels in malignant GCTs. Particularly high EPCAM levels were found in nonseminomatous GCTs such as YSTs (8.49) and choriocarcinoma (13.54). Immunohistochemical analysis verified gene expression data showing a distinct EPCAM staining in YST. Similarly in vitro, highest EPCAM expression was measured in GCT cell lines comprising yolk sac (2102Ep: 5.59) or choriocarcinoma (JAR: 10.65) components. This first comprehensive analysis of EPCAM in GCTs revealed high EPCAM expression in YSTs and choriocarcinomas. Thus, these nonseminomatous GCTs may be interesting targets for EPCAM immunotherapy, which has to be evaluated in further studies. |
| Schrappe M, Möricke A, Reiter A, Henze G, Welte K, Gadner H, Ludwig WD, Ritter J, Harbott J, Mann G, Klingebiel T, Gruhn B, Niemeyer C, Kremens B, Niggli F, Debatin KM, Ratei R, Stanulla M, Beier R, Cario G, Schrauder A, Zimmermann M |
Key Treatment Questions in Childhood Acute Lymphoblastic Leukemia: Results in 5 Consecutive Trials Performed by the ALL-BFM Study Group From 1981 to 2000. [+] |
Klinische Padiatrie 2013, 225(S 01):S62-S72 |
|
| Between 1981 and 2000, 6 609 children (<18 years of age) were treated in 5 consecutive trials of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). Patients were treated in up to 82 centers in Germany, Austria, and Switzerland. Probability of 10-year event-free survival (survival) improved from 65% (77%) in study ALL-BFM 81-78% (85%) in ALL-BFM 95. In parallel to relapse reduction, major efforts focused on reducing acute and late toxicity through advanced risk adaptation of treatment. The major findings derived from these ALL-BFM trials were as follows: 1) preventive cranial radiotherapy could be safely reduced to 12 Gy in T-ALL and high-risk ALL patients and eliminated in non-high-risk non-T-ALL patients, if it was replaced by high-dose and intrathecal methotrexate; 2) omission of delayed reintensification severely impaired outcome of low-risk patients; 3) 6 months less maintenance therapy caused an increase in systemic relapses; 4) slow response to an initial 7-day prednisone window was identified as adverse prognostic factor; 5) condensed induction therapy resulted in a significant improvement of outcome; 6) the daunorubicin dose in induction could be safely reduced in low-risk patients; 7) intensification of consolidation/reintensification treatment led to considerable improvement of outcome in high-risk patients. |
| Mannucci PM, Mancuso ME, Santagostino E |
How we choose factor VIII to treat hemophilia. [+] |
Blood 2012, 119: 4108 |
|
| In high-income countries, the large availability of coagulation factors for replacement therapy of patients with hemophilia A has raised the life expectancy of these lifelong bleeders to that of males from the general population. The practicing clinician is offered a multitude of choices among several commercial brands of factor VIII extracted from human plasma or engineered from mammalian cell cultures by means of recombinant DNA technology. This article has the goal to offer our opinions on how to choose among the different products, that we consider interchangeable relevant to their clinical efficacy in the control of bleeding and safety from pathogen transmission. Hence, the main determinants of our choices are price and the risk of occurrence of factor VIII inhibitory alloantibodies. With this as background, we present the rationale underlying the choices for different categories of patients with severe hemophilia A: previously untreated patients, multiply treated patients, and patients undergoing immune tolerance induction with large doses of factor VIII to eradicate inhibitors. Mention is also made to the possible strategies that should be implemented to make available coagulation factors for replacement therapy in developing countries. |
| Seeger K, Adams H, Buchwald D, Beyermann B, Kremens B, Niemeyer C, Ritter J, Schwabe D, Harms D, Schrappe M, Henze G |
TEL-AML1 fusion transcript in relapsed childhood acute lymphoblastic leukemia. The Berlin-Frankfurt-Münster Study Group. |
Blood 1998, 91: 1716 |
|
| Seeger K, Buchwald D, Peter A, Taube T, Stackelberg A, Schmitt G, Henze G |
TEL-AML1 fusion in relapsed childhood acute lymphoblastic leukemia. |
Blood 1999, 94: 374 |
|
| Seeger K, Buchwald D, Taube T, Peter A, Stackelberg A, Schmitt G, Köchling J, Henze G |
TEL-AML1 positivity in relapsed B cell precursor acute lymphoblastic leukemia in childhood. Berlin-Frankfurt-Münster Study Group [letter] [see comments]. |
Leukemia 1999, 13: 1469 |
|
| Seeger K, Stackelberg A, Taube T, Buchwald D, Körner G, Suttorp M, Dörffel W, Tausch W, Henze G |
Relapse of TEL-AML1-positive acute lymphoblastic leukemia in childhood. |
J Clin Oncol 2001, 19: 3188 |
|
| Seeger K, Viehmann S, Buchwald D, Harbott J, Schrappe M, Stary J, Henze G, Trka J |
Treatment response and residual-disease monitoring in initial and relapsed TEL-AML1 positive childhood ALL. |
Leukemia 2001, 15: 280 |
|
| Seidemann K, Meyer U, Jansen P, Yakisan E, Rieske K, Führer M, Kremens B, Schrappe M, Reiter A |
Impaired renal function and tumor lysis syndrome in pediatric patients with non-Hodgkin's lymphoma and B-ALL. Observations from the BFM-trials. |
Klin Pädiatr 1998, 210: 279 |
|
| Seidemann K, Tiemann M, Henze G, Sauerbrey A, Muller S, Reiter A |
Therapy for non-Hodgkin lymphoma in children with primary immunodeficiency. |
Med Pediatr Oncol 1999, 33: 536 |
|
| Seidemann K, Henze G, Beck J, Sauerbrey A, Kühl J, Mann G, Reiter A |
Non-Hodgkin's lymphoma in pediatric patients with chromosomal breakage syndromes (AT and NBS). |
Ann Oncol 2000, 11 Suppl 1: 141 |
|
| Seidemann K, Tiemann M, Schrappe M, Yakisan E, Simonitsch I, Janka-Schaub G, Dörffel W, Zimmermann M, Mann G, Gadner H, Parwaresch R, Riehm H, Reiter A |
Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. |
Blood 2001, 97: 3699 |
|
| Seidemann K, Tiemann M, Lauterbach I, Mann G, Simonitsch I, Stankewitz K, Schrappe M, Zimmermann M, Niemeyer C, Parwaresch R, Riehm H, Reiter A |
Primary mediastinal large B-cell lymphoma with sclerosis in pediatric and adolescent patients. |
J Clin Oncol 2003, 21: 1782 |
|
| Seidemann K, Zimmermann M, Book M, Meyer U, Burkhardt B, Welte K, Reiter A, Stanulla M |
Tumor necrosis factor and lymphotoxin alfa genetic polymorphisms and outcome in pediatric patients with non-Hodgkin's lymphoma: results from Berlin-Frankfurt-Münster Trial NHL-BFM 95. |
J Clin Oncol 2005, 23: 8414 |
|
| Seidel MG, Fritsch G, Matthes-Martin S, Lawitschka A, Lion T, Pötschger U, Rosenmayr A, Fischer G, Gadner H, Peters C |
In vitro and in vivo T-cell depletion with myeloablative or reduced-intensity conditioning in pediatric hematopoietic stem cell transplantation. [+] |
Haematologica 2005, 90: 1405 |
|
| BACKGROUND AND OBJECTIVES: Anti-thymocyte globulin (ATG) is given in various conditioning regimens for children and young adults undergoing hematopoietic stem cell transplantation (HSCT) from HLA non-identical donors in order to reduce the risks of graft-versus-host disease (GvHD) and rejection after the transplant. The aim of this study was to define the effect of in vitro T-cell depletion in addition to ATG on the reconstitution of T-cell-mediated immunity. DESIGN AND METHODS: We retrospectively analyzed the engraftment kinetics and clinical performance of 134 patients (median age 5.80 years) who received ATG during myeloablative or reduced intensity conditioning, and either in vitro T-cell-depleted or unmanipulated grafts. RESULTS: T-cell reconstitution was significantly delayed after T-cell-depleted grafts, irrespectively of the conditioning intensity (p<0.001). The incidence of fatal viral and fungal infections was higher in recipients of T-cell-depleted grafts than in those receiving unmanipulated grafts (26.6-29% versus |
| Seifert G, Kanitz JL, Pretzer K, Henze G, Witt K, Reulecke S, Voss A |
Improvement of Heart Rate Variability by Eurythmy Therapy After a 6-Week Eurythmy Therapy Training. [+] |
Integr Cancer Ther 2011, [Epub ahead of print] |
|
| Background. Eurythmy therapy (EYT) is a mind-body therapy used in anthroposophic medicine. Recently, the authors were able to show that at comparable workloads, EYT stimulated heart rate variability (HRV) whereas conventional ergometer training attenuated HRV. Furthermore, a long-term improvement of quality of life (QoL) and stress coping strategies by EYT could be shown. Objective. This study aimed to evaluate the long-term effects of EYT training on HRV. Design: A total of 23 healthy women (mean age = 44.57 ± 8.04 years) performed 10 hours of EYT over a period of 6 weeks. Electrocardiograms were recorded before and after the EYT trial. HRV was quantified by the extent of high (HF), low (LF), very low (VLF), and ultra low frequency (ULF) oscillations of heart rate. RESULTS: Autonomic regulation was significantly changed following the EYT training compared with baseline. Especially the proportion referring to the total power (P) of HF/P and LF/P increased, whereas ULF/P and (ULF+VLF)/P decreased after the training period. CONCLUSION: EYT shifted the autonomic regulation proportionally referring to the total power mainly caused by changes of ULF and VLF components of HRV. The LF and HF spectral components were also decreased following EYT while their proportion in relation to the total variance of the power spectrum was increased. The proportional enhancement of the higher frequency and the decrease of the ULF and VLF components are probably an indicator of an improvement of autonomic regulation processes by more relaxed physical activity after the EYT training, thus supporting the plausibility of the improved QoL and better stress coping strategies. |
| Seifert G, Rutkowski S, Jesse P, Madeleyn R, Reif M, Henze G, Längler A |
2. Anthroposophic Supportive Treatment in Children With Medulloblastoma Receiving First-line Therapy. [+] |
J Pediatr Hematol Oncol 2011, Epub ahead of print |
|
| BACKGROUND: The use of anthroposophic medicine (AM) is popular in Central Europe, especially in German-speaking countries. Although these therapies are judged to be beneficial by many patients, there are few data with regard to the safety and efficacy in pediatric oncology. Several theoretical concerns have been published with regard to tumor enhancement or promotion of metastatic dissemination due to mistletoe. To test the indirect safety of supportive anthroposophic treatment accompanying the first-line treatment in children with medulloblastoma in this respect we performed a retrospective matched-pair analysis of patients with medulloblastoma treated by standard first-line radiochemotherapy with or without a concomitantly applied panel of AM including mistletoe. The question was whether the effectiveness of the first-line therapy is altered by AM.
PROCEDURE: Seventeen patients with AM were matched in a 1:2 ratio with 34 patients from the database of the German HIT study group with regard to the criteria of diagnosis, age, status of metastatic dissemination, resection status, and first-line therapy.
RESULTS: The overall survival after 10 years was 58.33% for the AM group and 57.14% for the control group, that is, showing no statistically significant difference (stratified Cox regression; P=0.6023). Event-free survival (including metastases) also did not differ between the groups (stratified Cox regression; P=0.4275).
CONCLUSIONS: AM consisting of different combinations of specific pharmacologic and nonpharmacologic interventions seems to be safe with respect to any potential negative impact on the first-line therapy. There is no evidence with regard to tumor enhancement. The effectiveness of the supportive AM cannot be assessed on the basis of these data. |
| Seitz G, Dantonello TM, Int-Veen C, Blumenstock G, Godzinski J, Klingebiel T, Schuck A, Leuschner I, Koscielniak E, Fuchs J, on behalf of the CWS-96 Study Group |
Treatment efficiency, outcome and surgical treatment problems in patients suffering from localized embryonal bladder/prostate rhabdomyosarcoma: A report from the cooperative soft tissue sarcoma trial CWS-96. [+] |
Pediatr Blood Cancer 2011, 56: 718 |
|
| BACKGROUND: To analyze the clinical course, treatment modalities, complications and outcome of patients suffering from localized embryonal bladder/prostate rhabdomyosarcoma (BPRMS) treated on the CWS-96 trial.
PROCEDURE: There were 85 patients with BPRMS enrolled and 63 patients with embryonal non-metastatic BPRMS were analyzed. Fifty-six patients received neoadjuvant chemotherapy and response was assessed radiographically after 9 weeks. Local therapy with radiation and or surgery was performed based on age, tumor size, and response. Patients were treated with adjuvant chemotherapy following local control.
RESULTS: Patient's age ranged from 0 to 16 years with a median follow up of 5.3 years. Eighty nine percent of the patients had IRS group III disease. The 5-year overall survival (OS) for the whole group was 76.3 ± 5.6% and the 5-year event-free survival (EFS) 69.8 ± 6.2%. Seventeen patients underwent preoperative radiochemotherapy followed by tumor resection (5-year-OS: 87.8 ± 8.1%). Eight patients were treated with solely radiochemotherapy (87.5 ± 11.7%). Twenty-five patients received chemotherapy and tumor resection (OS: 83.6 ± 7.5%). Thirteen patients underwent incomplete tumor resection and were treated with radiochemotherapy postoperatively (OS: 39.9 ± 14.8%, P < 0.05 vs. other groups).
CONCLUSIONS: Local therapy is an important factor for prognosis of localized embryonal BPRMS. Inadequate primary or secondary surgery compromises the outcome and should be avoided. Radiotherapy alone, complete surgical tumor resection or combined preoperative radiotherapy with surgical resection lead to similar good local control rates and prognosis. Pediatr Blood Cancer 2011;56:718-724. © 2010 Wiley-Liss, Inc. |
| Selle B, Bar C, Hecker S, Schmidt-Rohr U, Viehmann S, Debatin K, Reinhardt D |
ABL-specific tyrosine kinase inhibitor imatinib as salvage therapy in a child with Philadelphia chromosome-positive acute mixed lineage leukemia (AMLL). |
Leukemia 2002, 16: 1393 |
|
| Selo N, Bölling T, Ernst I, Pape H, Martini C, Rübe C, Timmermann B, Fischedick K, Kortmann RD, Gerss J, Koch R, Willich N |
Acute toxicity profile of radiotherapy in 690 children and adolescents: RiSK data. [+] |
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 2010, 97: 119 |
|
| BACKGROUND AND PURPOSE: The "Registry for the evaluation of side effects after radiation in childhood and adolescence" (risk) was introduced to characterize adverse effects of radiotherapy in childhood and adolescence prospectively. The aim of this analysis was to characterize the pattern of acute side effects. MATERIALS AND METHODS: Since 2001, patients receiving radiotherapy in one of the German pediatric therapy trials have been registered in RiSK with detailed information regarding radiation doses to organs at risk and characterization of acute toxicities. RESULTS: From 2001 to May 2009, 690 patients have been characterized for acute toxicity in primary therapy. Acute toxicity ≥ grade 1 was observed in 506 patients. In patients irradiated in their lung and liver, patients with grade 1 or 2 acute toxicities showed higher organ volumes exposed to radiation doses <20 Gray (Gy) compared to patients without toxicities. For the salivary glands, there was a positive correlation between the acute toxicity grade and the maximum radiation dose to the organ; the lower GI tract showed a similar trend. The impact of different chemotherapy regimens on these acute side effects remains unclear. Age did not have any impact on side effects. CONCLUSION: This analysis gives a comprehensive overview of the acute toxicities of radiotherapy in children and adolescents. With prolongation of follow-up, detailed analyses regarding late toxicities will be possible with the characterization of dose-volume-effect relationships. |
| Sevenet N, Lellouch-Tubiana A, Schofield D, Hoang-Xuan K, Gessler M, Birnbaum D, Jeanpierre C, Jouvet A, Delattre O |
Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations. |
Hum Mol Genet 1999, 8: 2359 |
|
| Seyger M, Ritterbach J, Creutzig U, Gnekow A, Göbel U, Graf N, Reiter A, Lampert F, Harbott J |
12q13, a new recurrent breakpoint in acute non-lymphoblastic leukemia. |
Cancer Genet Cytogenet 1995, 80: 23 |
|
| Seyyedi S, Parlowsky T, Bucsky P |
Interimsanalyse der interdisziplinären multizentrischen Therapieoptimierungsstudie im Kindes- und Jugendalter, GPOH-MET 97. |
Monatsschr. Kinderheilk 2002, 150: 1303-1304. |
|
| Shannon KM, O'Connell P, Martin GA, Paderanga D, Olson K, Dinndorf P, McCormick F |
Loss of the normal NF1 allele from the bone marrow of children with type 1 neurofibromatosis and malignant myeloid disorders. |
N Engl J Med 1994, 330: 597 |
|
| Shalapour S, Eckert C, Seeger K, Pfau M, Prada J, Henze G, Blankenstein T, Kammertoens T |
Leukemia-associated genetic aberrations in mesenchymal stem cells of children with acute lymphoblastic leukemia. [+] |
Journal of molecular medicine 2010, 88: 249 |
|
| Childhood acute lymphoblastic leukemia (ALL) is caused by malignant immature lymphocytes. Even though childhood ALL can be cured in a large number of patients, around 20% of the patients suffer a relapse after chemotherapy. The origin of the relapse is unclear at the present time. Given the high plasticity of cells, we searched for leukemia-associated genetic aberrations and immunoglobulin (IG) gene rearrangements in mesenchymal stem cells (MSC) from childhood B-cell precursor ALL patients. MSC from all ten ALL patients analyzed presented the chromosomal translocations that had been detected in leukemia cells (TEL-AML1, E2A-PBX1, or MLL rearrangement). The proportions of translocation-positive MSC varied between 10% and 54% depending on the patients and the time point of analysis. Leukemia-specific IG gene rearrangements were detected in the MSC from three ALL patients. The detection of leukemia-associated genetic aberrations in MSC indicates a clonal relationship between MSC and leukemia cells and suggests their involvement in the pathogenesis and/or pathophysiology of childhood ALL. |
| Shalapour S, Hof J, Kirschner-Schwabe R, Bastian L, Eckert C, Prada J, Henze G, von Stackelberg A, Seeger K |
High VLA-4 expression is associated with adverse outcome and distinct gene expression changes in childhood B-cell precursor acute lymphoblastic leukemia at first relapse. [+] |
Haematologica 2011, 96: 1627 |
|
| Resistance to therapy and subsequent relapse remain major challenges in the clinical management of relapsed childhood acute lymphoblastic leukemia. As the bone marrow environment plays an important role in survival and chemotherapy resistance of leukemia cells by activating different signaling pathways, such as the VLA-4 and PI3K/Akt pathways, we studied the prognostic and biological impact of VLA-4 expression in leukemia cells from children with relapsed B-cell precursor acute lymphoblastic leukemia and its influence on the sensitivity of the leukemia cells to drugs. |
| Shen JJ, Williams BJ, Zipursky A, Doyle J, Sherman SL, Jacobs PA, Shugar AL, Soukup SW, Hassold TJ |
Cytogenetic and molecular studies of Down syndrome individuals with leukemia. |
Am J Hum Genet 1995, 56: 915 |
|
| Shimizu Y, Schull WJ, Kato H |
Cancer risk among atomic bomb survivors: the RERF Life Span Study. Radiation Effects Research Foundation. |
JAMA 1990, 264: 601 |
|
| Shi L, Eichelbauer D, Borchard F, Jürgens H, Göbel U, Schneider E |
Specificity and function of monoclonal antibodies directed against Ewing sarcoma cells. |
Cancer Immunol Immunother 1994, 38: 208 |
|
| Shields CL, Shields JA, Baez K, Cater JR, De Potter P |
Optic nerve invasion of retinoblastoma. Metastatic potential and clinical risk factors. [+] |
Cancer 1994, 73: 692 |
|
| BACKGROUND. Optic nerve invasion is one of the predictors for retinoblastoma metastases. This study was designed to investigate the risk of optic nerve invasion and clinical features that may identify those children with optic nerve invasion. METHODS. We reviewed the charts of 289 children with retinoblastoma treated initially with enucleation. Logistic regression analysis was performed to assess the risk for metastases from varying degrees of optic nerve invasion and to assess the clinical and histopathologic predictors of optic nerve invasion. RESULTS. There were 84 eyes (29%) with optic nerve invasion. The invasion was prelamina cribrosa in 44 cases (15%), up to but not posterior to the lamina cribrosa in 21 cases (7%), posterior to the lamina cribrosa but not to the cut end of the optic nerve in 17 cases (6%), and to the site of optic nerve transection in 2 cases (1%). Patients with optic nerve invasion were more likely to develop metastasis (P = 0.0016), particularly those with invasion to the postlaminar and cut section of the optic nerve (P = 0.0001). Development of metastasis was not statistically associated with laminar or prelaminar involvement. If those patients with choroidal invasion simultaneous with optic nerve invasion were excluded from evaluation, the presence of optic nerve invasion alone was not significant for development of metastasis. The clinical factors found to be predictive for optic nerve invasion from a univariate analysis included exophytic growth pattern (P = 0.011), elevated intraocular pressure (> 22 mm Hg) (P = 0.02), and tumor thickness greater than or equal to 15 mm (P = 0.03). The histopathologic factor significantly associated with optic nerve invasion (univariate analysis) was simultaneous choroidal invasion (P = 0.001). A trend toward an association with optic nerve invasion was found with vitreous hemorrhage (P = 0.06), iris neovascularization (P = 0.10), and poorly differentiated retinoblastoma (P = 0.07). A multivariate analysis showed the most significant clinical factors to be exophytic growth pattern (P = 0.002), tumor thickness greater than or equal to 15 mm (P = 0.01), and vitreous hemorrhage (P = 0.05). CONCLUSIONS. Optic nerve invasion of retinoblastoma beyond the lamina cribrosa is associated with a greater metastatic risk. Large exophytic retinoblastoma with secondary glaucoma is at highest risk for optic nerve invasion. |
| Shields CL, Shields JA, Needle M, de Potter P, Kheterpal S, Hamada A, Meadows AT |
Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma. [+] |
Ophthalmology 1997, 104: 2101 |
|
| OBJECTIVE: The purpose of the study is to investigate chemoreduction and adjuvant treatment (AT) for retinoblastoma and its effect on complete retinal tumor control, vitreous seed control, and subretinal seed control. DESIGN: The study design was a prospective, nonrandomized clinical trial. PARTICIPANTS: There were 130 intraocular retinoblastomas in 52 eyes of 32 consecutive patients observed for at least 1 year after initiation of treatment. INTERVENTION: Treatment with chemoreduction using vincristine, etoposide, and carboplatin (VEC) and adjuvant treatment (+ AT) (cryotherapy, laser photocoagulation, thermotherapy, chemothermotherapy, plaque radiation therapy, or external beam radiation therapy) were assessed. MAIN OUTCOME MEASURES: The effect of chemoreduction for 6 cycles (VEC x 6) versus fewer than 6 cycles (VEC x <6) on retinoblastoma control was analyzed. Furthermore, the impact of adjuvant treatment (+ AT) versus no adjuvant treatment (no AT) on retinoblastoma control was analyzed. RESULTS: Retinal tumors showed favorable initial regression with chemoreduction. Adjuvant treatment was applied to 93% of the retinal tumors after chemoreduction and only 2% recurred over the mean follow-up of 17 months (range 13-27 months). Vitreous seeds and subretinal seeds showed initial regression and often complete disappearance with chemoreduction. In those eyes with seeds before treatment, the addition of AT to VEC for 6 cycles decreased the vitreous seed recurrence from 75% to 0% (P = 0.04) and also decreased the subretinal seed recurrence from 67% to 0% (P = 0.003). More important, when considering that enucleation or external beam radiation therapy was the only other treatment option for these 52 eyes, the authors were successful in avoiding these methods in 42% of cases. Of the 36 eyes classified as Reese-Ellsworth group 5, there was 78% ocular salvage, and external beam radiation therapy was avoided in 25% of these eyes. There was a 100% ocular salvage in the group 5 eyes that received VEC for 6 cycles + AT to retinal tumors and seeds. CONCLUSIONS: Chemoreduction and AT to intraocular retinoblastoma and its seeds provides good retinal tumor control, even in eyes with advanced disease. Chemoreduction alone generally is not adequate to achieve complete tumor seed control. Cautious follow-up of affected patients is recommended because the risk for recurrent vitreous and subretinal seeds is substantial and proper treatment is critical for salvaging the eye. |
| Shields JA |
Importance of early diagnosis of retinoblastoma. |
The British journal of ophthalmology 1999, 83: 1315 |
|
| Shields CL, Honavar SG, Meadows AT, Shields JA, Demirci H, Naduvilath TJ |
Chemoreduction for unilateral retinoblastoma. [+] |
Archives of ophthalmology 2002, 120: 1653 |
|
| OBJECTIVE: To evaluate conservative management of unilateral retinoblastoma using chemoreduction and focal treatment. DESIGN: Prospective nonrandomized single-center clinical trial. SETTING: Ocular Oncology Service at Wills Eye Hospital of Thomas Jefferson University, Philadelphia, Pa, in conjunction with the Division of Oncology at The Children's Hospital of Philadelphia. PARTICIPANTS: Thirty eyes of 30 patients with unilateral retinoblastoma treated with chemoreduction between June 1, 1994, and August 31, 1999, that would otherwise have been managed with enucleation or external beam radiotherapy. INTERVENTION: All patients received treatment for retinoblastoma with a planned 6 cycles of chemoreduction using vincristine sulfate, etoposide, and carboplatin, combined with focal treatment (cryotherapy or thermotherapy) to each retinal tumor. MAIN OUTCOME MEASURES: The main outcome measure was the postchemoreduction need for external beam radiotherapy or enucleation. The cumulative probability of each outcome was estimated using Kaplan-Meier survival analysis. A secondary outcome measure was final visual acuity in the affected eye. The clinical features at the time of patient presentation were analyzed for their impact on the main outcomes using a series of Fisher exact tests and Cox proportional hazards regressions. RESULTS: Eighteen eyes (60%) were classified as having Reese-Ellsworth (RE) groups I through IV retinoblastoma and 12 eyes (40%), group V retinoblastoma. By using Kaplan-Meier estimates, we found a need for either external beam radiotherapy or enucleation in 68% of eyes by 5 years. In fact, 38% of those in groups I through IV required either treatment, whereas all of those in group V required the additional use of either treatment. Specifically, the need for external beam radiotherapy occurred in 27% of eyes by 5 years. Eleven percent of those in groups I through IV and 50% of group V required external beam radiotherapy by 5 years. The factors predictive of the need for external beam radiotherapy included RE group V disease, tumor thickness greater than 5 mm, and presence of vitreous seeds. The need for enucleation occurred in 47% of eyes by 5 years using Kaplan-Meier analysis. Specifically, 29% of those in groups I through IV and 67% of group V required enucleation by 5 years. The factors predictive of the need for enucleation included age at diagnosis older than 12 months, RE group V disease, tumor base diameter greater than 15 mm, and tumor thickness greater than 5 mm. At a mean follow-up of 29 months, the final visual acuity was 20/200 or better in 6 eyes (20%) and worse than 20/200 in 14 (47%); enucleation was needed in 10 (33%). Of the 26 eyes with initial macular involvement of retinoblastoma, final visual acuity was 20/200 or better in 6 (23%). No patient developed retinoblastoma metastasis, pinealoblastoma, or second malignant neoplasms. CONCLUSIONS: Chemoreduction is an option for selected eyes with unilateral retinoblastoma. Those with advanced RE group V retinoblastoma showed poorest results, while those with less advanced groups I through IV disease showed best results, maintaining the globe in 71% of eyes, sometimes with satisfactory functional visual acuity. |
| Shields CL, Shields JA |
Basic understanding of current classification and management of retinoblastoma. [+] |
Current opinion in ophthalmology 2006, 17: 228 |
|
| The current classification and management strategies for retinoblastoma are discussed. |
| Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, Shields JA |
The International Classification of Retinoblastoma predicts chemoreduction success. [+] |
Ophthalmology 2006, 113: 2276 |
|
| To evaluate the reliability of the International Classification of Retinoblastoma (ICRB) for predicting treatment success with chemoreduction (CRD). |
| Shields CL, Shields JA |
Retinoblastoma management: advances in enucleation, intravenous chemoreduction, and intra-arterial chemotherapy. [+] |
Current opinion in ophthalmology 2010, 21: 203 |
|
| To provide an update on current management of retinoblastoma |
| Shields CL, Shields JA |
Intra-arterial chemotherapy for retinoblastoma: the beginning of a long journey. [+] |
Clinical & experimental ophthalmology 2010, 38: 638 |
|
| Conservative management of retinoblastoma has evolved from external beam radiotherapy to systemic chemotherapy by intravenous route and now to localized chemotherapy by intra-arterial route in some cases. With 16-year experience, systemic chemotherapy has been found effective for minimal to moderately advanced retinoblastoma with tumour control of 90% or better, few side effects and even hope for return of some vision. Localized intra-arterial chemotherapy with delivery under fluoroscopy and catheterization of the ophthalmic artery is now undergoing evaluation and appears to provide striking control for retinoblastoma, particularly recurrent tumour seeds following other therapies. The limitations and complications of this approach have yet to be defined. Toxicity of the chemotherapy to the delicate retinal vessels is unknown. Despite its allure, intra-arterial chemotherapy should be used with caution, as in other fields of paediatric oncology it has been found to provide no advantage over intravenous chemotherapy. Time will tell. |
| Shu XO, Stewart P, Wen WQ, Han D, Potter JD, Buckley JD, Heineman E, Robison LL |
Parental occupational exposure to hydrocarbons and risk of acute lymphocytic leukemia in offspring. |
Cancer Epidemiol Biomarkers Prev 1999, 8: 783 |
|
| Siemer S, Lehmann J, Reinhard H, Graf N, Loffler G, Hendrik H, Remberger K, Stockle M |
Prenatal diagnosis of congenital mesoblastic nephroma associated with renal hypertension in a premature child. [+] |
International journal of urology : official journal of the Japanese Urological Association 2004, 11: 50 |
|
| In the present article, we report, for the first time, a prenatal diagnosis of a congenital mesoblastic nephroma in combination with a post-partum hyperreninemia with hypertension. A newborn was delivered at 35 weeks gestation who had an intrauterine diagnosis of a renal mass as early as 32 weeks gestational age by ultrasound examination. Tumor nephrectomy was performed on day 11 after delivery when an increase in hypertension was observed in the newborn. |
| Siepermann M, Koscielniak E, Dantonello T, Klee D, Boos J, Krefeld B, Borkhardt A, Hoehn T, Asea A, Wessalowski R |
Oral low-dose chemotherapy: Successful treatment of an alveolar rhabdomyosarcoma during pregnancy. [+] |
Pediatr Blood Cancer 2011, [Epub ahead of print] |
|
| We report for the first time the impact of neoadjuvant oral low-dose chemotherapy consisting of oral trofosfamide, idarubicin, and etoposide (O-TIE) in the case of alveolar rhabdomyosarcoma (RMS) in the lower jaw of an 18-year-old woman at 27 weeks of gestation, without fetal complications and a highly efficient anti-tumor response. Our study suggests the possible application of O-TIE treatment in a neoadjuvant setting during pregnancy and recommends a schedule that can be considered for the treatment of patients with high-risk sarcomas who cannot be treated with intensive chemotherapy for various reasons. Pediatr Blood Cancer © 2011 Wiley-Liss, Inc. |
| Siepermann M, Koscielniak E, Dantonello T, Klee D, Boos J, Krefeld B, Borkhardt A, Hoehn T, Asea A, Wessalowski R |
Oral low-dose chemotherapy: successful treatment of an alveolar rhabdomyosarcoma during pregnancy. [+] |
Pediatric blood & cancer 2012, 58: 104 |
|
| We report for the first time the impact of neoadjuvant oral low-dose chemotherapy consisting of oral trofosfamide, idarubicin, and etoposide (O-TIE) in the case of alveolar rhabdomyosarcoma (RMS) in the lower jaw of an 18-year-old woman at 27 weeks of gestation, without fetal complications and a highly efficient anti-tumor response. Our study suggests the possible application of O-TIE treatment in a neoadjuvant setting during pregnancy and recommends a schedule that can be considered for the treatment of patients with high-risk sarcomas who cannot be treated with intensive chemotherapy for various reasons. |
| Signorello LB, Mulvihill JJ, Green DM, Munro HM, Stovall M, Weathers RE, Mertens AC, Whitton JA, Robison LL, Boice JD Jr |
Congenital anomalies in the children of cancer survivors: a report from the childhood cancer survivor study. [+] |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2012 Jan 20; 30: 239 |
|
| Children with cancer receive mutagenic treatments, which raises concern about the potential transmissibility of germline damage to their offspring. This question has been inadequately studied to date because of a lack of detailed individual treatment exposure assessment such as gonadal radiation doses. |
| Silies H, Blaschke G, Hohenlochter B, Rossi R, Jürgens H, Boos J |
Excretion kinetics of ifosfamide side-chain metabolites in children on continuous and short-term infusion. |
Int J Clin Pharmacol Ther 1998, 36: 246 |
|
| Simon T, Hero B, Berthold F |
Testicular and paratesticular involvement by metastatic neuroblastoma. |
Cancer 2000, 88: 2636 |
|
| Simon A, Fleischhack G, Marklein G, Ritter J |
Antimicrobial prophylaxis of bacterial infections in pediatric oncology patients. |
Klin Pädiatr 2001, 213 Suppl 1:A22-A37 |
|
| Simon T, Voth E, Berthold F |
Asymmetric salivary gland 123I-meta-iodobenzylguanidine uptake in a patient with cervical neuroblastoma and Horner syndrome. |
Med Pediat Oncol 2001, 36: 489 |
|
| Simon A, Fleischhack G |
Non-pharmacologic strategies to prevent and control infectious complications in pediatric hematology/oncology patients. |
Klin Pädiatr 2001, 213 Suppl 1:A9-A21 |
|
| Simon T, Hero B, Dupuis W, Selle B, Berthold F |
The incidence of hearing impairment after successful treatment of neuroblastoma. |
Klin Pädiatr 2002, 214: 149 |
|
| Simon A |
Evidenzbasierte Empfehlungen zur Anwendung dauerhafter, zentralvenöser intravaskulärer Zugänge in der pädiatrischen Onkologie. |
mhp-Verlag Wiesbaden 2002 |
|
| Simon T, Hero B, Berthold F |
Diagnostik und Therapie des Neuroblastoms. |
Kinder- und Jugendmedizin 2003, 1: 31 |
|
| Simon T, Hero B, Hunneman DH, Berthold F |
Tumour markers are poor predictors for relapse or progression in neuroblastoma. [+] |
European journal of cancer (Oxford, England : 1990) 2003, 39: 1899 |
|
| The value of the tumour markers vanillylmandelic acid (VMA) and homovanillic acid (HVA) in urine (u) and serum (s), neurone-specific enolase (NSE), and lactate dehydrogenase (LDH) in the early prediction of relapse/progression in neuroblastoma is not known. We analysed the data of neuroblastoma patients who had successfully completed first-line treatment and had laboratory results available from their initial diagnosis and from relapse/progression (n=196). Patients' overall survival from relapse or progression was 21.5+/-4.2% (mean+/-standard deviation). At diagnosis, we found abnormal results in 75% for VMA and/or HVA (s), 92% for VMA and/or HVA (u), 90% for NSE, and 81% for LDH. We found a lower incidence of abnormal results at relapse or progression with 40% for VMA and/or HVA (s), 54% for HVA and/or VMA (u), 61% for NSE, and 48% for LDH. Sensitivity of all markers was higher for metastatic compared with local recurrence. NSE was the best, being able to detect 42% of the localised relapses, 77% of the combined local/metastatic relapses, and 69% of the metastatic recurrences. Relapse or progression in neuroblastoma cannot be detected reliably by monitoring tumour markers alone. Therefore, follow-up of neuroblastoma patients must include clinical assessment and imaging studies. |
| Simon T, Spitz R, Faldum A, Hero B, Berthold F |
New definition of low-risk neuroblastoma using stage, age, and 1p and MYCN status. [+] |
Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology 2004, 26: 791 |
|
| Data from patients with localized and stage 4S neuroblastoma were analyzed to define a new, extended low-risk group that does not require postoperative chemotherapy. Nine hundred eight patients with stage 1 to 3 and 4S disease without MYCN amplification were included. The prognostic impacts of age, stage, serum lactate dehydrogenase (LDH) activity, histology, and alterations of chromosomes 1p, 11q, and 3p were analyzed. By univariate analysis, alterations of chromosomes 1p and 11q were correlated with poor event-free survival (EFS) and overall survival (OS). Chromosome 3p alterations were prognostic only for EFS. Age, stage, and histology were found prognostic for EFS and OS. Stage 3 patients older than 2 years showed the worst outcome and were excluded from multivariate analysis. By multivariate analysis, status of 1p (P = 0.005, hazard ratio [HR] 3.6) and 11q (P = 0.024, HR 2.8) proved prognostic for EFS but only 1p status (P = 0.009, HR 3.0) for OS. The new low-risk group was defined as no MYCN amplification and either stage 1, stage 2 without 1p alterations, stage 3 two years of age or younger without 1p alteration, or stage 4S. These patients had a better outcome (3-year EFS 88.0 +/- 1.3%, 3-year OS 97.4 +/- 0.6%) than stage 2 and 3 patients with 1p alterations and stage 3 patients older than 2 years (3-year EFS 51.7 +/- 6.5%, P < 0.001; 3-year OS 83.4 +/- 4.5%; P < 0.001). The authors conclude that postoperative chemotherapy is required only in a small group of patients with localized and stage 4S disease without MYCN amplification. |
| Simon T, Hero B, Faldum A, Handgretinger R, Schrappe M, Niethammer D, Berthold F |
Consolidation treatment with chimeric anti-GD2-antibody ch14. 18 in children older than 1 year with metastatic neuroblastoma. [+] |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2004, 22: 3549 |
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| PURPOSE: Antibody treatment is considered tolerable and potentially effective in the therapy of neuroblastoma. We have analyzed stage 4 neuroblastoma patients older than 1 year who underwent consolidation treatment with the chimeric monoclonal anti-GD2-antibody ch14.18. PATIENTS AND METHODS: Stage 4 patients older than 1 year who completed initial treatment without event were eligible. ch14.18 was scheduled in a dose of 20 mg/m2/d during 5 days in six cycles every 2 months. Patients who did not receive ch14.18 served as controls. RESULTS: Of 334 assessable patients, 166 received ch14.18, 99 received a 12-month low-dose maintenance chemotherapy (MT) instead, and 69 had no additional treatment. During 695 ch14.18 cycles, fever (55% of cycles), abnormal C-reactive protein without infection (35%), cough (24%), rash (22%), and pain (16%) were the main side effects. Univariate analysis found similar event-free survival (EFS) for the three groups (3-year EFS, 46.5% +/- 4.1%, 44.4% +/- 4.9%, 37.1% +/- 5.9% for patients treated with antibody ch14.18, MT, and no additional therapy, respectively; log-rank test, P =.314). For overall survival (OS), ch14.18 treatment (3-year OS, 68.5% +/- 3.9%) was superior to MT (3-year OS, 56.6% +/- 5.0%) or no additional therapy (3-year OS, 46.8% +/- 6.2%; log-rank test, P =.018). Separate univariate analysis of patients with autologous stem-cell transplantation revealed no difference between patients with ch14.18 treatment and no additional consolidation. Multivariate analysis failed to demonstrate an advantage of antibody treatment for EFS and OS. CONCLUSION: Consolidation treatment of stage 4 neuroblastoma with ch14.18 was associated with considerable but manageable side effects. Compared with oral maintenance chemotherapy and no consolidation treatment, ch14.18 had no clear impact on the outcome of patients. |
| Simon A, Beutel K, Marklein G, Fleischhack G |
Bacterial infections in pediatric cancer patients. |
Klin Pädiatr 2005, 217 Suppl 1:S17 |
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| Simon T, Hero B, Faldum A, Handgretinger R, Schrappe M, Niethammer D, Berthold F |
Infants with stage 4 neuroblastoma: the impact of the chimeric anti-GD2-antibody ch14. 18 consolidation therapy. [+] |
Klinische Padiatrie 2005, 217: 147 |
|
| BACKGROUND: Antibody treatment is considered tolerable and potentially effective in the therapy of neuroblastoma. We have analyzed the clinical data of infants < 1 year with stage 4 neuroblastoma with regard to the consolidation treatment. PATIENTS AND METHODS: Infants < 1 year with stage 4 neuroblastoma who completed initial treatment (6-8 chemotherapy cycles followed either by 4 cycles low dose oral chemotherapy or high dose chemotherapy with stem cell transplantation) without event were eligible for this trial. Consolidation therapy consisted of 6 cycles of antibody ch14.18 (20 mg/m(2) x d ch14.18 for 5 days every 2 months) or 12 months oral maintenance chemotherapy (MT). RESULTS: Of 59 evaluable patients, 31 received a total of 159 ch14.18 cycles, 16 received MT instead, and 12 had no further treatment. Fever (47 % of cycles), abnormal CRP without infection (25 %), rash (23 %), cough (16 %), and pain (8 %) were the main side effects. Univariate analysis found no difference in event free survival (3-year-EFS 80.5 +/- 7.1 %, 87.5 +/- 8.3 %, and 75.0 +/- 12.5 % for patients treated with antibody ch14.18, MT, and no further therapy, p = 0.433) and overall survival (3-year-OS 90.1 +/- 5.4 %, 93.8 +/- 6.0 %, and 91.7 +/- 8.0 % for patients treated with antibody ch14.18, MT, and no further therapy, p = 0.931). Multivariate analysis failed to demonstrate an advantage of antibody treatment. CONCLUSION: The outcome of infants with stage 4 neuroblastoma is good. Consolidation treatment with ch14.18 was tolerable but associated with fever, elevated CRP, rash, cough, and pain as side effects. Compared to oral maintenance chemotherapy and no consolidation treatment, ch14.18 treatment had no impact on the patients' outcome which confirms the results found in children > 1 year. |
| Simon T, Hero B, Bongartz R, Schmidt M, Müller RP, Berthold F |
Intensified external-beam radiation therapy improves the outcome of stage 4 neuroblastoma in children > 1 year with residual local disease. [+] |
Strahlentherapie und Onkologie 2006, 182: 389 |
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| BACKGROUND AND PURPOSE: In neuroblastoma, the value of radiation therapy in high-intensive first-line treatment protocols is still not exactly known but radiation-associated long-term effects need to be considered. The impact of external-beam radiation therapy (EBRT) on event-free (EFS) and overall survival (OS) of stage 4 neuroblastoma patients of the NB97 trial was analyzed. PATIENTS AND METHODS: The authors retrospectively analyzed data of 110 stage 4 neuroblastoma patients > or = 1 year who underwent induction therapy and high-dose chemotherapy with stem cell transplantation without relapse. Intensified local EBRT (36 Gy) of the residual tumor volume was reserved for patients with residual viable tumor documented by MRI and corresponding metaiodobenzylguanidine (MIBG) uptake. RESULTS: 13 patients who received EBRT for local residual disease had similar outcome (3-year EFS 85 +/- 10%, 3-year OS 92 +/- 7%) as 74 patients without any MIBG residual (3-year EFS 61 +/- 6%, 3-year OS 75 +/- 6%). Outcome was worse in 23 children without EBRT to residual primary (3-year EFS 25 +/- 10%, 3-year OS 51 +/- 11%). Separate analysis of 14 patients with isolated localized residual disease found far better outcome of eight patients with EBRT (3-year EFS 100%, 3-year OS 100%) compared to six patients without EBRT (3-year EFS 20 +/- 18%, 3-year OS 20 +/- 18%). Multivariate analysis identified EBRT as influential on EFS (hazard ratio 0.27) and OS (hazard ratio 0.17) in addition to MYCN amplification and presence of primary tumor site MIBG residual. CONCLUSION: EBRT appeared effective in high-intensive treatment of stage 4 neuroblastoma. It seems to compensate the disadvantage of incomplete response to induction chemotherapy. These retrospective results need confirmation by a prospective randomized trial. |
| Simon T, Längler A, Berthold F, Klingebiel T, Hero B |
Topotecan and etoposide in the treatment of relapsed high-risk neuroblastoma: results of a phase 2 trial. [+] |
Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology 2007, 29: 101 |
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| We initiated a phase 2 trial with a combination of topotecan and etoposide (TE) in patients with relapse after intensive first line chemotherapy for neuroblastoma. TE chemotherapy consisted of topotecan (schedule A: 1.0 mg/m2/d 30-minute-infusion days 1 to 5, B: 0.7 mg/m2/d continuous infusion days 1 to 7, and C: 1.0 mg/m2/d continuous infusion days 1 to 7) followed by etoposide (100 mg/m2/d 1-hour-infusion days 8 to 10). TE was repeated every 28 days. The treatment was continued until severe nonhematopoietic toxicity or progression occurred or the treating physician chose alternative consolidation treatment after response to TE. Forty patients received 153 TE cycles. Grades 3 to 4 leukopenia was frequently observed in all schedules (A 51% of cycles, B 48%, and C 74%, P=0.141). Thrombocytopenia (A 69%, B 63%, and C 93%, P=0.004) and neutropenic fever (A 12%, B 29%, and C 37%, P=0.048) occurred more frequently in schedule C. No treatment-related fatal toxicity was observed. Among 36 patients evaluable for response, 4 patients achieved complete and 13 patients achieved partial remission (47%). We conclude that the combination of TE is effective and tolerable in the treatment of relapsed high-risk neuroblastoma. |
| Simon T, Längler A, Harnischmacher U, Frühwald MC, Jorch N, Claviez A, Berthold F, Hero B |
Topotecan, cyclophosphamide, and etoposide (TCE) in the treatment of high-risk neuroblastoma. Results of a phase-II trial. [+] |
Journal of cancer research and clinical oncology 2007, 133: 653 |
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| PURPOSE: Relapsed high-risk neuroblastoma patients still have a poor prognosis. This phase-II trial assessed a new topotecan containing chemotherapy approach in patients with active disease. METHODS: Chemotherapy consisted of topotecan (1.0 mg/m(2)/day 168-h continuous infusion), cyclophosphamide (100 mg/m(2)/day 1-h-infusion days 1-7 starting 6 h prior to topotecan), and etoposide (100 mg/m(2)/day 1-h-infusion days 8-10). Patients with relapsed neuroblastoma were scheduled for six cycles, untreated patients for two cycles followed by standard high-risk treatment. RESULTS: Main toxicity observed during 153 cycles were grade 3-4 leukopenia (97% of cycles), thrombocytopenia (92%), neutropenic fever (52%), and mucositis (10%). No treatment related fatal toxicity occurred. Complete or partial response was achieved in 19 of 31 (61%) evaluable relapsed patients and 8 of 11 (72%) untreated patients. CONCLUSIONS: The combination of topotecan, cyclophosphamide, and etoposide is tolerable and effective in relapsed and untreated neuroblastoma. Myelotoxicity is the main side effect but seems justified in view of the encouraging response rates. A randomized phase-III trial in primary disease has been commenced. |
| Simon T, Berthold F, Borkhardt A, Kremens B, De Carolis B, Hero B |
Treatment and outcomes of patients with relapsed, high-risk neuroblastoma: results of German trials. [+] |
Pediatr Blood Cancer 2011, 56: 578 |
|
| BACKGROUND:
The prognosis of high-risk neuroblastoma patients has improved over the last decades. However, many patients experience relapse after successful initial treatment. We retrospectively analyzed the long-term outcome of relapsed patients of three consecutive national neuroblastoma trials.
METHODS:
Patients were included when they fulfilled all of the following criteria: Age at diagnosis being 1 year or older, first diagnosis between 1990 and 2007, stage 4 disease or stage 3 neuroblastoma with MYCN amplification, and relapse or progression after successful first-line autologous stem cell transplantation (ASCT).
RESULTS:
A total of 451 high-risk neuroblastoma patients 1 year or older underwent ASCT during first-line treatment, 253 experienced recurrence of disease, 158 received salvage chemotherapy, and 23 of them finally underwent a second ASCT. These 23 patients had a better median survival (2.08 years) and 3-year survival rate from recurrence (43.5 ± 10.9%) compared to 74 patients who had no second chemotherapy (median survival 0.24 years, 3-year survival rate 4.0 ± 2.6%) and 135 patients who underwent second-line chemotherapy but did not undergo second ASCT (median survival of 0.89 years, 3-year survival rate 9.6 ± 2.8%, P < 0.001). By February 2010, 3/23 patients were in complete remission, 3/23 in very good partial remission, 1/23 in partial remission, 14/23 patients died of disease after successful second ASCT, and 2/23 died of complications due to second ASCT.
CONCLUSION:
Intensive second-line therapy is feasible. A small subgroup of relapsed high-risk neuroblastoma patients may benefit from intensive relapse chemotherapy and second ASCT. The potential of long-term survival justifies clinical trials on intensive second-line treatment. |
| Simon T, Hero B, Faldum A, Handgretinger R, Schrappe M, Klingebiel T, Berthold F |
Long term outcome of high-risk neuroblastoma patients after immunotherapy with antibody ch14. 18 or oral metronomic chemotherapy. [+] |
BMC Cancer 2011, 18; 11: 21. |
|
| BACKGROUND: The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB) ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort.
METHODS: A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide). In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months). Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69) served as controls.
RESULTS: The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098). In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038). The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4%) compared to NB90 MT (34 ± 5%, p = 0.026) and to no consolidation (35 ± 6%, p = 0.019). Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found.
CONCLUSIONS: Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective. |
| Simon T, Niemann CA, Hero B, Henze G, Suttorp M, Schilling FH, Berthold F |
Short- and long-term outcome of patients with symptoms of spinal cord compression by neuroblastoma. [+] |
Developmental medicine and child neurology 2012, 54: 347 |
|
| Prospective trials on neuroblastoma-induced myelopathy are lacking. Therefore, we retrospectively analysed patients in four national neuroblastoma trials. |
| Skolin I, Axelsson K, Ghannad P, Hernell O, Wahlin YB |
Nutrient intake and weight development in children during chemotherapy for malignant disease. |
Oral Oncol 1997, 33 : 364 |
|
| Skokowa J, Germeshausen M, Zeidler C, Welte K |
Severe congenital neutropenia: inheritance and pathophysiology. [+] |
Current opinion in hematology 2007, 14: 22 |
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| Severe congenital neutropenia is a heterogeneous disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10/l. In this review we summarize our current knowledge on inheritance and pathophysiolgy of congenital neutropenia. |
| Skokowa J, Lan D, Thakur BK, Wang F, Gupta K, Cario G, Brechlin AM, Schambach A, Hinrichsen L, Meyer G, Gaestel M, Stanulla M, Tong Q, Welte K |
NAMPT is essential for the G-CSF-induced myeloid differentiation via a NAD(+)-sirtuin-1-dependent pathway. [+] |
Nature medicine 2009, 15: 151 |
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| We identified nicotinamide phosphoribosyltransferase (NAMPT), also known as pre-B cell colony enhancing factor (PBEF), as an essential enzyme mediating granulocyte colony-stimulating factor (G-CSF)-triggered granulopoiesis in healthy individuals and in individuals with severe congenital neutropenia. Intracellular NAMPT and NAD(+) amounts in myeloid cells, as well as plasma NAMPT and NAD(+) levels, were increased by G-CSF treatment of both healthy volunteers and individuals with congenital neutropenia. NAMPT administered both extracellularly and intracellularly induced granulocytic differentiation of CD34(+) hematopoietic progenitor cells and of the promyelocytic leukemia cell line HL-60. Treatment of healthy individuals with high doses of vitamin B3 (nicotinamide), a substrate of NAMPT, induced neutrophilic granulocyte differentiation. The molecular events triggered by NAMPT include NAD(+)-dependent sirtuin-1 activation, subsequent induction of CCAAT/enhancer binding protein-alpha and CCAAT/enhancer binding protein-beta, and, ultimately, upregulation of G-CSF synthesis and G-CSF receptor expression. G-CSF, in turn, further increases NAMPT levels. These results reveal a decisive role of the NAD(+) metabolic pathway in G-CSF-triggered myelopoiesis. |
| Slavc I, Urban C, Ritter J, Ambros P, Haas O, Köller U, Kurz R |
Paraparesis secondary to a spinal mass as the presenting feature of erythroleukaemia in a 10-month-old child. |
Eur J Pediatr 1992, 151: 332 |
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| Sluga M, Windhager R, Lang S, Heinzl H, Bielack S, Kotz R |
Local and systemic control after ablative and limb sparing surgery in patients with osteosarcoma. |
Clin Orthop 1999, 120 |
|
| Smith MA, Seibel NL, Altekruse SF, Ries LA, Melbert DL, O'Leary M, Smith FO, Reaman GH |
Outcomes for children and adolescents with cancer: challenges for the twenty-first century. [+] |
Journal of clinical oncology 2010, 28: 2625 |
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| PURPOSE: This report provides an overview of current childhood cancer statistics to facilitate analysis of the impact of past research discoveries on outcome and provide essential information for prioritizing future research directions. METHODS: Incidence and survival data for childhood cancers came from the Surveillance, Epidemiology, and End Results 9 (SEER 9) registries, and mortality data were based on deaths in the United States that were reported by states to the Centers for Disease Control and Prevention by underlying cause. RESULTS: Childhood cancer incidence rates increased significantly from 1975 through 2006, with increasing rates for acute lymphoblastic leukemia being most notable. Childhood cancer mortality rates declined by more than 50% between 1975 and 2006. For leukemias and lymphomas, significantly decreasing mortality rates were observed throughout the 32-year period, though the rate of decline slowed somewhat after 1998. For remaining childhood cancers, significantly decreasing mortality rates were observed from 1975 to 1996, with stable rates from 1996 through 2006. Increased survival rates were observed for all categories of childhood cancers studied, with the extent and temporal pace of the increases varying by diagnosis. CONCLUSION: When 1975 age-specific death rates for children are used as a baseline, approximately 38,000 childhood malignant cancer deaths were averted in the United States from 1975 through 2006 as a result of more effective treatments identified and applied during this period. Continued success in reducing childhood cancer mortality will require new treatment paradigms building on an increased understanding of the molecular processes that promote growth and survival of specific childhood cancers. |
| Smith-Whitley, Kim, Thompson, Alexis A |
Indications and complications of transfusions in sickle cell disease. [+] |
Pediatric blood & cancer 2012, 59, 358 |
|
| Red cell transfusion remains an important part of the management of acute and chronic complications in SCD. The ongoing and emerging uses of transfusions in SCD may have significant benefits; however, the potential complications of transfusions also deserve careful consideration. In this report we review current indications for transfusions, transfusion complications, modifications of transfusion practices to mitigate risk, and potential considerations to improve transfusion outcomes. |
| Smoots DW, Geyer JR, Lieberman DM, Berger MS |
Predicting disease progression in childhood cerebellar astrocytoma. |
Childs Nerv Syst 1998, 14: 636 |
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| Soling A, Schurr P, Berthold F |
Expression and clinical relevance of NY-ESO-1, MAGE-1 and MAGE-3 in neuroblastoma. |
Anticancer Res 1999, 19: 2205 |
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| Sommet J, Missud F, Holvoet L, Ithier G, Lorrot M, Benkerrou M, Faye A |
Morbidity among child travellers with sickle-cell disease visiting tropical areas: an observational study in a French tertiary care centre. [+] |
Archives of disease in childhood 2013, epub ahead of print |
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| OBJECTIVE: To examine morbidity among children with sickle-cell disease (SCD) during and after travel to a tropical area. DESIGN: Observational study. SETTING: Tertiary care children; Robert Debré Hospital, Paris, France. POPULATION: Children with SCD younger than 18 years old and managed in the SCD referral centre at the Robert Debré Hospital who travelled to a tropical or subtropical area between 1 June 2009 and 31 December 2009. MAIN OUTCOME: To assess morbidity, we used the number of clinical events requiring medical consultation during the trip as the primary outcome and the number of hospitalisations required after returning as the secondary outcome. RESULTS: Thirty-nine children were included. The median age was 7.8 years (4.3-11.7 years). All of the children and their parents attended a pretravel visit focusing on the prevention of travel-related diseases. Twelve children (30%) consulted a physician while they were abroad. Thirteen children (33%) were hospitalised, and 23 children (59%) consulted a physician while they were abroad or within 3 months after returning to France. Considering the 3 months before and after travel, the number of children hospitalised after travel (n=12, 30.7%) was significantly higher than the number hospitalised before (n=4, 10.2%; p=0.01). One child was hospitalised for multifocal osteoarthritis as a complication of Salmonella enterica septicaemia of gastrointestinal origin. CONCLUSIONS: Travels to tropical areas are associated with high morbidity in children with SCD. Salmonella infection is a particularly significant threat, and empirical antibiotic therapy should be prescribed routinely for traveller's diarrhoea in this population. |
| Sonnemann J, Eckervogt V, Truckenbrod B, Boos J, Winkelmann W, van Valen F |
The bisphosphonate pamidronate is a potent inhibitor of Ewing's sarcoma cell growth in vitro. |
Anticancer Drugs 2003, 14: 767 |
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| Sperling C, Büchner T, Creutzig U, Ritter J, Harbott J, Fonatsch C, Sauerland C, Mielcarek M, Löffler H, Ludwig W |
Clinical, morphologic, cytogenetic and prognostic implications of CD34 expression in childhood and adult de novo AML. |
Leukemia and Lymphoma 1995, 17: 417 |
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| Spix C, Aareleid T, Stiller C, Magnani C, Kaatsch P, Michaelis J |
Survival of children with neuroblastoma. time trends and regional differences in Europe, 1978--1992. |
Eur J Cancer 2001, 37: 722 |
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| Spitz R, Hero B, Westermann F, Ernestus K, Schwab M, Berthold F |
Fluorescence in situ hybridization analyses of chromosome band 1p36 in neuroblastoma detect two classes of alterations. |
Genes Chromosomes Cancer 2002, 34: 299 |
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| Spitz R, Hero B, Ernestus K, Berthold F |
FISH analyses for alterations in chromosomes 1, 2, 3, and 11 define high-risk groups in neuroblastoma. |
Med Pediatr Oncol 2003, 41: 30 |
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| Spitz R, Hero B, Ernestus K, Berthold F |
Deletions in chromosome arms 3p and 11q are new prognostic markers in localized and 4s neuroblastoma. |
Clin Cancer Res 2003, 9: 52 |
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| Spix C, Michaelis J, Berthold F, Erttmann R, Sander J, Schilling F |
Lead-time and overdiagnosis estimation in neuroblastoma screening. |
Stat Med 2003, 22: 2877 |
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| Spix C, Schüz J, Klein G, Kaatsch P |
Epidemiologie solider Tumoren im Kindes- und Jugendalter. |
Kinder- und Jugendmedizin 2003, 4 |
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| Spitz R, Hero B, Ernestus K, Berthold F |
Gain of distal chromosome arm 17q is not associated with poor prognosis in neuroblastoma. [+] |
Clinical cancer research : an official journal of the American Association for Cancer Research 2003, 9: 4835 |
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| PURPOSE: In several studies, gain of the distal long arm of chromosome 17 was shown to be a frequent and prognostically relevant factor in neuroblastoma, in addition to MYCN amplification (MNA) or 1p deletion. We asked whether this observation could be confirmed in a German cohort. EXPERIMENTAL DESIGN: To evaluate the frequency and prognostic impact of 17q gain, we investigated tissue samples from 193 neuroblastoma patients by the use of fluorescence in situ hybridization. The DNA probe (MPO) was located in distal 17q in the region of interest as used by several groups. To analyze the association of patients' outcome with the breakpoint position within 17q, we used the more proximal DNA probe ERBB2 in 17q21 on a selected number of cases. Gain was defined as an excess of 17q material compared with the chromosome 17 centromere in at least 50% of the analyzed tumor cells. In addition, alterations in chromosomes 1p, 3p, and 11q, as well as MYCN status, were determined to describe the interrelationship between the different parameters and to evaluate an independent prognostic influence. RESULTS: Gain of 17q was found in 61% of the investigated tumors. An additional 23% displayed an excess of 17q in less than half of all cells. Gain correlated with stage 4 disease (P = 0.003) and with other chromosomal alterations, such as 1p (P < 0.001), 3p (P = 0.01), 11q (P = 0.001), and MNA (P = 0.016), as well as with increased patient age (P = 0.01). Outcome was not different between patients with 17q gain compared with those without, however. A prognostic influence could not be delineated in all stages or in localized or in stage 4 subgroups or in the MYCN nonamplified patient cohort. Outcome did not differ between patients with additional 17q material in <10% of the cells or in >70%. Patients showing a breakpoint in the more proximal part of 17q could not be described as having a more favorable outcome compared with patients with a more distal breakpoint. Prognosis was poor in patients with MNA and/or 11q loss either with or without 17q gain. A multivariate analysis including the chromosomal parameters 17q, 11q, and MYCN status, as well as stage, showed MYCN and 11q status (P < 0.001), but not 17q or stage as significant prognostic factors. CONCLUSION: Although the most frequent aberration in neuroblastoma to date, we found no association between 17q gain and an inferior prognosis in our cohort; the status of MYCN and 11q, however, allowed reliable prediction of patients' outcomes. |
| Spitz R, Hero B, Skowron M, Ernestus K, Berthold F |
MYCN-status in neuroblastoma: characteristics of tumours showing amplification, gain, and non-amplification. [+] |
European journal of cancer (Oxford, England : 1990) 2004, 40: 2753 |
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| While the role of MYCN-amplification (MNA) for risk assessment in neuroblastoma is undisputed, the phenomenon of gene copy excess below the amplification threshold is rarely described. To discuss biological characteristics and the clinical impact of the so-called MYCN-gain versus amplified or non-amplified cases, we investigated the MYCN status of 659 patients uniformly analysed by fluorescence in situ hybridisation. The number of MYCN-amplified tumours in our cohort was 18% (116/659); an additional 38 tumours (6%) displayed MYCN-gain. Both alterations were associated with an advanced stage disease, an increased patient age and further chromosomal alterations. Most of the amplified neuroblastomas displayed 1p aberrations, whereas MYCN-gain tumours correlated with 11q alterations. In contrast to the amplified cases, tumours with gain displayed no increased MYCN RNA levels. MNA versus non-amplification discriminated between good and poor outcomes, independent of stage, age and the degree of amplification. However, patients with amplified tumours showed a significantly better outcome when this was combined with non-stage 4 disease and age <1 year versus stage 4 and age < 1 year. Although MYCN-gain was associated with poor event-free-survival (EFS) in stages 1-3, 4S (P=0.005), this might be related to associated genetic aberrations and not to the MYCN-gain itself. A survival difference between neuroblastomas with gain and single copy MYCN could not be delineated. In conclusion, MNA predicts a poor outcome for neuroblastoma patients of all stages and age. MYCN-gain is also a characteristic feature of advanced stage tumours and older patients, but is not associated with higher MYCN expression and appears not to be discriminative in predicting patient outcome. |
| Spitz R, Hero B, Simon T, Berthold F |
Loss in chromosome 11q identifies tumors with increased risk for metastatic relapses in localized and 4S neuroblastoma. [+] |
Clinical cancer research 2006, 12(11 Pt 1): 3368 |
|
| PURPOSE: To improve risk prediction in neuroblastoma and to specify the type of a possible relapse, alterations in the long arm of chromosome 11 were analyzed. EXPERIMENTAL DESIGN: A representative cohort of 611 neuroblastomas was investigated for deletion events in distal chromosome 11q using interphase fluorescence in situ hybridization. RESULTS: Alterations in 11q were found in 159 of 611 tumors in the whole cohort (26%) and were associated with stage 4 disease (P < 0.001) and age at diagnosis of >2.5 years (P < 0.001). Event-free survival and overall survival were significantly poorer for patients with 11q loss in the whole cohort (event-free survival and overall survival, P < 0.001) and in different subsets: neuroblastoma without MYCN amplification (MNA) (event-free survival and overall survival, P < 0.001), with MNA (event-free survival, P = 0.03; overall survival, P = 0.02), and MYCN-nonamplified stage 1, 2, 3, and 4S tumors with and without del 1p (event-free survival and overall survival, P < 0.001). In stage 4, the 11q status did not discriminate outcome. By multivariate analysis, the 11q status proved prognostic for event-free survival in the whole cohort (P = 0.008; hazard ratio, 1.573) and in the subgroup of stages 1, 2, 3, and 4S without MNA (P < 0.001; hazard ratio, 3.534). Moreover, 11q alterations were strongly correlated with the occurrence of metastatic relapses (P < 0.001). CONCLUSION: In addition to the current risk stratification, the status of 11q enables the identification of patients with an increased risk for relapses in general and metastatic relapses in particular. |
| Spitz R, Oberthuer A, Zapatka M, Brors B, Hero B, Ernestus K, Oestreich J, Fischer M, Simon T, Berthold F |
Oligonucleotide array-based comparative genomic hybridization (aCGH) of 90 neuroblastomas reveals aberration patterns closely associated with relapse pattern and outcome. [+] |
Genes, chromosomes & cancer 2006, 45: 1130 |
|
| The study of genomic alterations in neuroblastoma is of particular importance since several cytogenetic markers proved to be closely associated with the clinical phenotype. To disclose patterns of gains and losses, we performed high-resolution oligonucleotide array-based comparative genomic hybridization (aCGH). A total cohort of 90 patients was classified into 6 subsets according to tumor stage and outcome: Stages 1-3+ (with event), Stage 1-3- (no event), Stage 4+/-, and Stage 4S+/-. The aberration patterns in Stages 1-3- and 4S- tumors differed from all other groups as they were predominantly characterized by losses (3, 4, 14, X) and gains (7, 17) of whole chromosomes. However, 59/65 (91%) tumors of Stages 1-3+ or Stage 4 revealed numerous structural copy number alterations (sCNA). While deletions in chromosomes 1, 3, and 11 discriminated outcome in Stage 4, there were no specific sCNA that distinguished tumor stage within the subgroup of unfavorable tumors. sCNA in 1p, 3p, 11q, 17q, or MYCN amplification (MNA) was seen among 22/24 patients who died, 10/12 with metastatic relapses, and 5/9 with local recurrences. Detailed breakpoint analyses on chromosomes 1, 3, 11, and 17 disclosed preferred breaking areas, although breakpoints were not identical. Amplifications were found in 18 patients and involved 2p24 (MYCN) and other segments of chromosome 2, as well as regions on chromosome arms 6q, 12q, and 17q. One single feature in 21q21.1 (BU678720, without known function yet) attracted particular attention since five patients showed a homozygous loss of this sequence. |
| Spitz R, Betts DR, Simon T, Boensch M, Oestreich J, Niggli FK, Ernestus K, Berthold F, Hero B |
Favorable outcome of triploid neuroblastomas: a contribution to the special oncogenesis of neuroblastoma. [+] |
Cancer genetics and cytogenetics 2006, 167: 51 |
|
| There is a well-known association between patient outcome and tumor ploidy in neuroblastoma. To date, however, most clinical trials have not used this parameter for therapy stratification. Using conventional cytogenetics and fluorescence in situ hybridization (FISH), we investigated 36 tumors in terms of ploidy and chromosome 1 copy number (polysomy). In addition, interphase FISH for polysomy was performed on a second cohort of 440 neuroblastomas, together with the status of 1p, MYCN, and 11q. The main goals were as follows: (1) to assess the reliability of FISH to determine ploidy; (2) to illustrate associations between somy 1 and clinical/biologic factors; and (3) to investigate the role of somy 1 for predicting outcome. The comparison between karyotyping and FISH in the smaller cohort revealed 86% consistency between ploidy and polysomy (31/36). According to FISH, trisomic tumors in the second cohort showed structural chromosomal aberrations less frequently compared to di-/tetrasomic tumors (15 vs. 60%, P < 0.001). The portion of trisomic neuroblastomas was higher in stages 1, 2, and 4S versus stages 3 and 4 (55 vs. 24%, P < 0.001) and in children 18 months or younger versus those older than 18 months (55 vs. 19%, P < 0.001). Prognosis was significantly better for trisomic tumors versus di-/tetrasomic in the whole cohort [event-free (EFS) and overall survival (OS), P < 0.001]. In the subgroup without abnormalities of other molecular markers, EFS of trisomic neuroblastomas was better (P = 0.048), but was most likely due to an unequal stage distribution. In further subgroups, in terms of age and stage, significance between the somy groups was not reached, neither for EFS nor OS. The multivariate analyses including age, stage, chromosomal markers, and somy 1 confirmed the lack of independent prognostic power for the copy number of chromosome 1. This study demonstrates the following: (1) FISH is a practical alternative to other more labor-intensive techniques for determining ploidy; (2) trisomic tumors correlate with younger age at diagnosis, localized stage, and the lack of structural alterations; and (3) polysomy is not an independent prognostic marker. The sharp decline of trisomic tumors after the age of 18 months supports the idea of different genetic tumor entities. |
| Spix C, Schmiedel S, Kaatsch P, Schulze-Rath R, Blettner M |
Case-control study on childhood cancer in the vicinity of nuclear power plants in Germany 1980-2003. [+] |
European journal of cancer (Oxford, England : 1990) 2008, 44: 275 |
|
| The 1984 Windscale study raised concern about a possible association between living in the vicinity of nuclear power plants and childhood cancer. No such effect for all cancers was seen in ecological studies in Germany (1980-1995). Results from exploratory analyses led to a new study. Pre-selected areas around all 16 major nuclear power plants in Germany formed the study area. The design is a matched case-control study; cases are all cancers under five years diagnosed in 1980-2003: 1592 cases, and 4735 controls. Inverse distance of place of residence to the nearest nuclear power plant at the time of diagnosis was used as the independent variable in a conditional logistic regression model. Results show an increased risk for childhood cancer under five years when living near nuclear power plants in Germany. The inner 5-km zone shows an increased risk (odds ratio 1.47; lower one-sided 95% confidence limit 1.16). The effect was largely restricted to leukaemia. The results are compatible with the corresponding subgroups in the previous German ecological studies, with which this study shares most of the cases. They contrast with the lack of an effect observed or expected from other studies due to low doses from routine nuclear power plant operation. |
| Spix C, Spallek J, Kaatsch P, Razum O, Zeeb H |
Cancer survival among children of Turkish descent in Germany 1980-2005: a registry-based analysis. [+] |
BMC cancer 2008, 8: 355 |
|
| BACKGROUND: Little is known about the effect of migrant status on childhood cancer survival. We studied cancer survival among children of Turkish descent in the German Cancer Childhood Registry, one of the largest childhood cancer registries worldwide. METHODS: We identified children of Turkish descent among cancer cases using a name-based approach. We compared 5-year survival probabilities of Turkish and other children in three time periods of diagnosis (1980-87, 1988-95, 1996-2005) using the Kaplan-Meier method and log-rank tests. RESULTS: The 5-year survival probability for all cancers among 1774 cases of Turkish descent (4.76% of all 37.259 cases) was 76.9% compared to 77.6% in the comparison group (all other cases; p = 0.15). We found no age- or sex-specific survival differences (p-values between p = 0.18 and p = 0.90). For the period 1980-87, the 5-year survival probability among Turkish children with lymphoid leukaemia was significantly lower (62% versus 75.8%; p < 0.0001), this remains unexplained. For more recently diagnosed leukaemias, we saw no survival differences for Turkish and non-Turkish children. CONCLUSION: Our results suggest that nowadays Turkish migrant status has no bearing on the outcome of childhood cancer therapies in Germany. The inclusion of currently more than 95% of all childhood cancer cases in standardised treatment protocols is likely to contribute to this finding. |
| Spix C, Schulze-Rath R, Kaatsch P, Blettner M |
Case-control study on risk factors for leukaemia and brain tumours in children under 5 years in Germany. [+] |
Klinische Padiatrie 2009, 221: 362 |
|
| In the context of a case control study on the cancer risk for children under five by distance to the nearest nuclear power plant, we collected information on other risk factors in a subset. We present the interview study as if it had been an independent study. Parents of 471 cases with Leukaemia, Lymphoma or CNS (Central Nervous System)-tumour from the German Childhood Cancer Registry, diagnosed at age under 5 in the years 1993-2003, and 1,457 matched controls were to be interviewed. For Leukaemia, 243 cases/604 controls, and for CNS 102 cases/246 controls participated, lymphoma cases were too few. Questions related to social status, ionizing radiation, pregnancy and birth, immune system, and selected toxins. The analysis is exploratory in nature; variables were selected by backward elimination. For leukaemia we found a significant protective effect of social contacts (OR=0.50, 95% CI [0.29;0.87]) and a risk for high birth weight (OR=1.96 95% CI [1.12;3.41] comparing >4,000 g to |
| Spix C, Mergenthaler A, Kaatsch P |
[Data exchange between the German Childhood Cancer Registry and the Epidemiological Cancer State Registries]. |
Klinische Padiatrie 2009, 221: 398 |
|
| Spix C, Kaatsch P, Blettner M |
The German and the French studies on childhood leukemia and nuclear power: differences and similarities. |
International journal of cancer 2012, [Epub ahead of print] |
|
| Spix C |
Fertility in survivors of childhood cancer. |
Deutsches Arzteblatt international 2012, 109: 124 |
|
| Sposto R, Ertel IJ, Jenkin RD, Boesel CP, Venes JL, Ortega JA, Evans AE, Wara W, Hammond D |
The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Childrens Cancer Study Group. |
J Neurooncol 1989, 7: 165 |
|
| Spycher BD, Feller M, Zwahlen M, Röösli M, von der Weid NX, Hengartner H, Egger M, Kuehni CE |
Childhood cancer and nuclear power plants in Switzerland: A census based cohort study. |
Int J Epidemiol 2011 Jul 12. [Epub ahead of print] |
|
| Stansfeld AG, Diebold J, Noel H, Kapanci Y, Rilke F, Kelenyi G, Sundstrom C, Lennert K, van Unnik JA, Mioduszewska O, et al. |
Updated Kiel classification for lymphomas. |
Lancet 1988, 1: 292 |
|
| Stahnke K, Ritter J, Schellong G, Beck J, Kabisch H, Lampert F, Creutzig U |
Rezidivbehandlung bei akuter myeloischer Leukämie im Kindesalter. Eine retrospektive Analyse der in der Studie AML-BFM- 83 aufgetretenen Rezidive. |
Klinische Pädiatrie 1992, 204: 253 |
|
| Stahnke K, Creutzig U, Ritter J, Group for |
Second remission in relapsed childhood acute myelogenous leukemia after pretreatment with the AML-BFM-83 protocol. |
Haematology and Blood Transfusion 1993, 36: 500 |
|
| Stahnke K, Ritter J, Boos J, Creutzig U |
Mitoxantrone-etoposide or HD-Ara-C/mitoxantrone for remission induction in children with first relapse of AML. |
Haematology and Blood Transfusion 1996,V: 200 |
|
| Stahnke K, Boos J, Bender-Götze C, Ritter J, Zimmermann M, Creutzig U |
Duration of first remission predicts remission rates and longterm survival in children with relapsed acute myelogenous leukemia. |
Leukemia 1998, 12: 1543 |
|
| Stanulla M, Loning L, Welte K, Schrappe M |
Secondary brain tumours in children with ALL. |
Lancet 1999, 354: 1126 |
|
| Stanulla M, Kasper B, Schrappe M, Viehmann S, Harbott J, Ludwig W, Welte K |
Granulocyte colony-stimulating factor receptor expression and 11q23/MLL genotype in childhood acute lymphoblastic leukemia developing during the first 18 months of life. |
Leukemia 2000, 14: 337 |
|
| Stanulla M, Schrappe M, Brechlin A, Zimmermann M, Welte K |
Polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia. |
Blood 2000, 95: 1222 |
|
| Stanulla M, Stumm M, Dieckvoss B, Seidemann K, Schemmel V, Müller-Brechlin A, Schrappe M, Welte K, Reiter A |
No evidence for a major role of heterozygous deletion 657del5 within the NBS1 gene in the pathogenesis of non-Hodgkin's lymphoma of childhood and adolescence. |
Br J Haematol 2000, 109: 117 |
|
| Stanulla M, Schrauder A, Welte K, Schrappe M |
Tumor necrosis factor and lymphotoxin-alpha genetic polymorphisms and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia. |
BMC Blood Disord 2001, 1 |
|
| Stam R, Den Boer M, Meijerink J, Ebus M, Peters G, Noordhuis P, Janka-Schaub G, Armstrong S, Korsmeyer S, Pieters R |
Differential mRNA expression of Ara-C-metabolizing enzymes explains Ara-C sensitivity in MLL gene-rearranged infant acute lymphoblastic leukemia. |
Blood 2003, 101: 1270 |
|
| Stams W, Den Boer M, Beverloo H, Meijerink J, Stigter R, van Wering E, Janka-Schaub G, Slater R, Pieters R |
Sensitivity to L-asparaginase is not associated with expression levels of asparagine synthetase in t(12;21)+ pediatric ALL. |
Blood 2003, 101: 2743 |
|
| Stam R, MM van, Den Boer M, Ebus M, Janka-Schaub G, Allen J, Pieters R |
Multidrug resistance genes in infant acute lymphoblastic leukemia. |
Leukemia 2004, 18: 78 |
|
| Stams WA, den Boer ML, Holleman A, Appel IM, Beverloo HB, van Wering ER, Janka-Schaub GE, Evans WE, Pieters R |
Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia. [+] |
Blood 2005, 105: 4223 |
|
| Resistance to L-asparaginase in leukemic cells may be caused by an elevated cellular expression of asparagine synthetase (AS). Previously, we reported that high AS expression did not correlate to L-asparaginase resistance in TEL-AML1-positive B-lineage acute lymphoblastic leukemia (ALL). In the present study we confirmed this finding in TEL-AML1-positive patients (n = 28) using microarrays. In contrast, 35 L-asparaginase-resistant TEL-AML1-negative B-lineage ALL patients had a significant 3.5-fold higher AS expression than 43 sensitive patients (P < .001). Using real-time quantitative polymerase chain reaction (RTQ-PCR), this finding was confirmed in an independent group of 39 TEL-AML1-negative B-lineage ALL patients (P = .03). High expression of AS was associated with poor prognosis (4-year probability of disease-free survival [pDFS] 58% +/- 11%) compared with low expression (4-year pDFS 83% +/- 7%; P = .009). We conclude that resistance to l-asparaginase and relapse risk are associated with high expression of AS in TEL-AML1-negative but not TEL-AML1-positive B-lineage ALL. |
| Stams WA, den Boer ML, Beverloo HB, Meijerink JP, van Wering ER, Janka-Schaub GE, Pieters R |
Expression levels of TEL, AML1, and the fusion products TEL-AML1 and AML1-TEL versus drug sensitivity and clinical outcome in t(12;21)-positive pediatric acute lymphoblastic leukemia. [+] |
Clinical cancer research 2005, 11: 2974 |
|
| PURPOSE: t(12;21)(p13; q22), present in approximately 25% of pediatric precursor B-ALL, is highly sensitivity to L-asparaginase and the prognosis depends on the intensity of the treatment protocol. This study analyzes the relationship between the mRNA expression of the genes and fusion products involved in t(12;21), in vitro sensitivity to prednisolone, vincristine, and L-asparaginase, and long-term clinical outcome in t(12;21)+ acute lymphoblastic leukemia (ALL) patients. EXPERIMENTAL DESIGN: Long-term clinical outcome in 45 t(12;21)+ ALL patients was related to mRNA expression of TEL, AML1, TEL-AML1, and AML1-TEL, determined by real-time quantitative PCR, and the in vitro sensitivity to prednisolone, vincristine, and L-asparaginase, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. RESULTS: A significant approximately 3.5-fold lower TEL expression in t(12;21)+ compared with t(12;21)- ALL samples (P = 0.006) and normal controls (P = 0.004) was found. Expression of AML1 did not differ between t(12;21)+ and t(12;21)- ALL. However, AML1 expression in the leukemic cells was 2-fold higher compared with normal controls (P = 0.02). The TEL-AML1 fusion product was expressed in all t(12;21)+ cases, whereas the reciprocal fusion product AML1-TEL was expressed in only 76%. High expression levels of TEL-AML1 [hazard ratio (HR), 1.3; 95% confidence interval (95% CI), 1.10-1.57; P = 0.003], AML1-TEL (HR, 4.9; 95% CI, 1.99-12.40; P = 0.001) and AML1 (HR, 1.1; 95% CI, 1.03-1.22; P = 0.006) were associated with a poor long-term clinical outcome within t(12;21)+ ALL. Cellular drug resistance towards prednisolone, vincristine, and L-asparaginase could not explain this predictive value. Multivariate analysis including age and WBC showed that only high AML1-TEL expression is an independent poor prognostic factor in t(12;21)+ childhood ALL. CONCLUSION: High AML1-TEL expression is an independent poor prognostic factor in t(12;21)+ childhood ALL. |
| Stanulla M, Seidemann K, Schnakenberg E, Book M, Mehles A, Welte K, Schrappe M, Reiter A |
Methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and risk of pediatric non-Hodgkin lymphoma in a German study population. |
Blood 2005, 105: 906 |
|
| Stanulla M, Schaeffeler E, Flohr T, Cario G, Schrauder A, Zimmermann M, Welte K, Ludwig WD, Bartram CR, Zanger UM, Eichelbaum M, Schrappe M, Schwab M |
Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia. [+] |
JAMA 2005, 293: 1485 |
|
| CONTEXT: Early response to multiagent chemotherapy, including mercaptopurine, as measured by minimal residual disease is an important prognostic factor for children with acute lymphoblastic leukemia (ALL). Thiopurine methyltransferase (TPMT) is involved in the metabolism of mercaptopurine and subject to genetic polymorphism, with heterozygous individuals having intermediate and homozygous mutant individuals having very low TPMT activity. OBJECTIVE: To assess the association of TPMT genotype with minimal residual disease load before and after treatment with mercaptopurine in the early treatment course of childhood ALL. DESIGN, SETTING, AND PATIENTS: TPMT genotyping of childhood ALL patients (n = 814) in Germany consecutively enrolled in the ALL-BFM (Berlin-Frankfurt-Münster) 2000 study from October 1999 to September 2002. Minimal residual disease was analyzed on treatment days 33 and 78 for risk-adapted treatment stratification. A 4-week cycle of mercaptopurine was administered between these 2 minimal residual disease measurements. Patients (n = 4) homozygous for a mutant TPMT allele, and consequently deficient in TPMT activity, were treated with reduced doses of mercaptopurine and, therefore, not included in the analyses. MAIN OUTCOME MEASURES: Minimal residual disease load before (day 33) and after (day 78) mercaptopurine treatment. Loads smaller than 10(-4) were defined as negative. RESULTS: Patients (n = 55) heterozygous for allelic variants of TPMT conferring lower enzyme activity had a significantly lower rate of minimal residual disease positivity (9.1%) compared with patients (n = 755) with homozygous wild-type alleles (22.8%) on day 78 (P = .02). This translated into a 2.9-fold reduction in risk for patients with wild-type heterozygous alleles (relative risk, 0.34; 95% confidence interval, 0.13-0.86). CONCLUSIONS: TPMT genotype has a substantial impact on minimal residual disease after administration of mercaptopurine in the early course of childhood ALL, most likely through modulation of mercaptopurine dose intensity. Our findings support a role for minimal residual disease analyses in the assessment of genotype-phenotype associations in multiagent chemotherapeutic trials. |
| von Stackelberg A, Henze G |
Rezidive der akuten lymphoblastischen Leukämie. |
In: Gadner H, Gaedicke G, Niemeyer C, Ritter J, editors. Pädiatrische Hämatologie und Onkologie Berlin, Heidelberg, New York: Springer Verlag Springer Verlag, 2006, 680 |
|
| Stanulla M, Cario G, Meissner B, Schrauder A, Möricke A, Riehm H, Schrappe M |
Integrating molecular information into treatment of childhood acute lymphoblastic leukemia--a perspective from the BFM Study Group. [+] |
Blood cells, molecules & diseases 2007, 39: 160 |
|
| Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood and is treated with chemotherapy alone or, in particular subgroups, with additional radiation therapy and/or stem cell transplantation. The treatment intensity is adjusted according to prognostic factors associated with the risk of ALL recurrence. On Berlin-Frankfurt-Münster (BFM) protocols, the widely applicable early in vivo response to treatment as measured by the reduction of leukemic cells in the blood or bone marrow is currently the most important prognostic factor. However, although overall long-term cure rates for childhood ALL treated on risk-adapted protocols have dramatically improved over the last decades and, to date, are higher than 75%, a significant number of patients still die due to recurrent disease or the toxicity of treatment applied. One goal in future BFM trials will be to take advantage of a better molecular understanding of leukemia and host characteristics to dissect the mechanisms underlying the differences in treatment response. This short review focuses on the evolution of treatment response in BFM trials and provides a perspective on our strategy for improving molecular characterization of childhood ALL and implementing more individualized and novel therapeutic approaches. |
| Staege MS, Banning-Eichenseer U, Weissflog G, Volkmer I, Burdach S, Richter G, Mauz-Körholz C, Föll J, Körholz D |
Gene expression profiles of Hodgkin's lymphoma cell lines with different sensitivity to cytotoxic drugs. [+] |
Experimental hematology 2008, 36: 886 |
|
| OBJECTIVE: The prognosis of patients with Hodgkin's lymphoma (HL) has been significantly improved as a result of combination treatment including chemotherapy. However, some patients are refractory to chemotherapy. Therefore, identification of new targets might be useful for development of alternative treatment strategies. In addition, identification of markers associated with chemoresistance can be used to identify patients with increased risk of relapse. MATERIALS AND METHODS: By using high-density DNA microarrays, we analyzed the gene-expression profile of HL-cell lines in comparison to a set of normal tissues. Furthermore, we tested the sensitivity of HL cells for cytotoxic drugs (cisplatin, etoposide, melphalan) and compared the gene-expression profile of chemotherapy-resistant and -sensitive cell lines. Differentially expressed genes were validated by polymerase chain reaction and flow cytometry. RESULTS: In addition to genes with high expression in all cell lines, we observed differences between the gene-expression profile of chemotherapy-resistant and -sensitive cells. Genes upregulated in resistant cells include cytokine receptors (IL5RA, IL13RA1), markers expressed on antigen-presenting cells (CD40, CD80), as well as genes with known association to chemoresistance, e.g., myristoylated alanine-rich protein kinase C substrate. In addition, the tumor antigen PRAME (preferentially expressed antigen in melanoma) was expressed in resistant cell lines only. CONCLUSION: Genes with high expression in HL cells might be potential targets for development of future therapeutic interventions. Expression of tumor antigens together with costimulatory molecules in chemotherapy-resistant HL cells might become targets for cytotoxic T-cell responses against HL cells. |
| von Stackelberg A, Hartmann R, Bührer C, Fengler R, Janka-Schaub G, Reiter A, Mann G, Schmiegelow K, Ratei R, Klingebiel T, Ritter J, Henze G, ALL-REZ BFM Study Group |
High-dose compared with intermediate-dose methotrexate in children with a first relapse of acute lymphoblastic leukemia. [+] |
Blood 2008, 111: 2573 |
|
| High-dose methotrexate (MTX) has been extensively used for treatment of acute lymphoblastic leukemia (ALL). To determine the optimal dose of MTX in childhood relapsed ALL, the ALL Relapse Berlin-Frankfurt-Münster (ALL-REZ BFM) Study Group performed this prospective randomized study. A total of 269 children with a first early/late isolated (n = 156) or combined (n = 68) bone marrow or any isolated extramedullary relapse (n = 45) of precursor B-cell (PBC) ALL (excluding very early marrow relapse within 18 months after initial diagnosis) were registered at the ALL-REZ BFM90 trial and randomized to receive methotrexate infusions at either 1 g/m(2) over 36 hours (intermediate dose, ID) or 5 g/m(2) over 24 hours (high dose, HD) during 6 (or 4) intensive polychemotherapy courses. Intensive induction/consolidation therapy was followed by cranial irradiation, and by conventional-dose maintenance therapy. Fifty-five children received stem-cell transplants. At a median follow-up of 14.1 years, the 10-year event-free survival probability was .36 (+/- .04) for the ID group (n = 141), and .38 (+/- .04) for the HD group (n = 128, P = .919). The 2 groups did not differ in terms of prognostic factors and other therapeutic parameters. In conclusion, methotrexate infusions at 5 g/m(2) per 24 hours, compared with 1 g/m(2) per 36 hours, are not associated with increased disease control in relapsed childhood PBC acute lymphoblastic leukemia. |
| Stanulla M, Schaeffeler E, Möricke A, Coulthard SA, Cario G, Schrauder A, Kaatsch P, Dördelmann M, Welte K, Zimmermann M, Reiter A, Eichelbaum M, Riehm H, Schrappe M, Schwab M |
Thiopurine methyltransferase genetics is not a major risk factor for secondary malignant neoplasms after treatment of childhood acute lymphoblastic leukemia on Berlin-Frankfurt-Münster protocols. [+] |
Blood 2009, 114: 1314 |
|
| Thiopurine methyltransferase (TPMT)is involved in the metabolism of thiopurines such as 6-mercaptopurine and 6-thioguanine. TPMT activity is significantly altered by genetics, and heterozygous and even more homozygous variant people reveal substiantially decreased TPMT activity. Treatment for childhood acute lymphoblastic leukemia (ALL) regularly includes the use of thiopurine drugs. Importantly, childhood ALL patients with low TPMT activity have been considered to be at increased risk of developing therapy-associated acute myeloid leukemia and brain tumors. In the present study, we genotyped 105 of 129 patients who developed a secondary malignant neoplasm after ALL treatment on 7 consecutive German Berlin-Frankfurt-Münster trials for all functionally relevant TPMT variants. Frequencies of TPMT variants were similarly distributed in secondary malignant neoplasm patients and the overall ALL patient population of 814 patients. Thus, TPMT does not play a major role in the etiology of secondary malignant neoplasm after treatment for childhood ALL, according to Berlin-Frankfurt-Münster strategies. |
| Stanulla M, Schrappe M |
Treatment of childhood acute lymphoblastic leukemia. [+] |
Seminars in hematology 2009, 46: 52 |
|
| Childhood acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. Studies in ALL have been a model for clinical and basic research beyond pediatric hemato-oncology. As a result of sustained and well-organized research efforts since the early 1960s, childhood ALL now can be successfully treated in about 80% of patients by the application of intensive combination chemotherapy regimens, which in specific patient subgroups may need to be supplemented with radiation therapy and/or hematopoietic stem cell transplantation. Triggered by the observation of specific clinical presenting features, biological characteristics, and early treatment response being associated with treatment outcome, therapy intensity in contemporary ALL protocols is adjusted according to prognostic factors predicting the risk of relapse. While the goal of effective therapy for the majority of children with ALL has been achieved, significant numbers of patients still die due to recurrent disease or the toxicity of treatment. Thus, future research must extend our molecular understanding of leukemia and host factors in order to even more specifically identify the mechanisms underlying the differences in treatment response and outcome, and to finally address the therapeutic needs of the individual child. |
| Staege MS, Körholz D |
New treatment strategies for Hodgkin's lymphoma. |
Leukemia research 2009, 33: 886 |
|
| von Stackelberg A, Völzke E, Kühl JS, Seeger K, Schrauder A, Escherich G, Henze G, Tallen G, for the ALL-REZ BFM Study Group |
Outcome of children and adolescents with relapsed acute lymphoblastic leukaemia and non-response to salvage protocol therapy: A retrospective analysis of the ALL-REZ BFM Study Group. [+] |
European journal of cancer 2011, 47: 90 |
|
| AIM OF THE STUDY: Non-response (NR) to treatment of childhood relapsed acute lymphoblastic leukaemia (ALL) is an end-point of protocol therapy. Subsequent management has not yet been standardised. This study analyses different approaches after NR to aid optimising future strategies. PATIENTS AND METHODS: Ninety-three children with NR to treatment according to ALL relapse-protocols of the Berlin/Frankfurt/Muenster (BFM) Study Group (03/1990-2006/1999) were retrospectively assigned to a curative (C: intensive polychemotherapies, stem cell transplantation (SCT); n=51), palliative (P: 1-2 antineoplastic agents; n=23) or supportive (S: no antineoplastic therapy; n=19) treatment approach. RESULTS: Median survival after diagnosis of NR were 121 (C), 89 (P) and 42 (S) days, respectively (p<0.001). In cohort C, a complete remission (2ndCR) was obtained in 16/51 patients, among these 13 only after SCT, and nine children achieved partial remission. Ten of the 51 patients died from treatment-related complications, 39/51 from disease progression. Today, two patients are still in continuous CR after SCT. Adverse prognostic factors were overrepresented in the non-curative cohorts. Time-point of relapse and treatment after NR were independent predictors of survival duration. Most patients without antineoplastic treatment died at home, the majority of the others in the hospital. CONCLUSIONS: Treatment after NR has been heterogeneous and customised. Therapies with curative intent are capable of inducing 2ndCR but associated with high treatment-related morbidity, -mortality and minimal survival. NR patients may, therefore, be ideal candidates for controlled phase I/II trials, thus offering them a chance to benefit from new drugs and promoting drug development for cohorts with better prognosis. |
| Stahl M, Ranft A, Paulussen M, Bölling T, Vieth V, Bielack S, Görtitz I, Braun-Munzinger G, Hardes J, Jürgens H, Dirksen U |
19. Risk of recurrence and survival after relapse in patients with Ewing sarcoma. [+] |
Pediatr Blood Cancer 2011,Epub ahead of print |
|
| BACKGROUND:
The prognosis in patients with relapsed Ewing sarcoma is unfavorable. Our investigation identifies factors predicting for the outcome following relapse.
PROCEDURE:
We analyzed type of relapse, time to relapse and overall survival after relapse (OSr) in 714 patients with first recurrence. All patients had been treated within the Cooperative Ewing Sarcoma Studies (CESS) 81 or 86, or the European Intergroup CESS (EICESS 92). OSr time was calculated from diagnosis of first relapse to last follow-up or death.
RESULTS:
Median follow-up time from diagnosis of primary disease was 2.2 years (mean = 4.0; range: 0.2-24.9). Relapse sites were local in 15%, combined local and systemic in 12%, and systemic in 73%. Among patients with a localized primary tumor, 20% relapsed locally, while 12% showed combined and 68% systemic relapse. When the primary disease was disseminated, 82% developed systemic, 13% combined, and 5% local relapse. Five-year OSr was 0.13 (SE = 0.01). Outcome following local relapse, with a 5-year survival rate of 0.24 (P < 0.001), was superior to outcome after systemic or combined recurrence. Five-year OSr was 0.07 (SE = 0.01) in patients who relapsed 0-2 years after the diagnosis of primary disease, as compared to a 5-year OSr of 0.29 (SE = 0.03) when relapse occurred later.
CONCLUSIONS:
5-year OSr in Ewing sarcoma is poor (<0.2). Prognostically favorable factors are: late onset (>2 years) and strictly localized relapse. |
| Stanulla M, Bourquin JP |
Behandlung der akuten lymphoblastischen Leukämie im Kindesalter. |
Pharm unserer Zeit 2012, 3 |
|
| Steinberg S, Hartmann R, Wisniewski S, Berger K, Beck J, Henze G |
Late sequelae of CNS recurrence of acute lymphoblastic leukemia in childhood. |
Klin Pädiatr 1998, 210: 200 |
|
| Steiner M, Burkart W, Grosche B, Kaletsch U, Michaelis J |
Trends in infant leukaemia in West Germany in relation to in utero exposure due to Chernobyl accident. |
Radiat Environ Biophys 1998, 37: 87 |
|
| Steinbach D, Dörffel W, Eggers G, Holfeld E, Kluba U, Krause I, Lauterbach I, Reiss T, Rieske K, Scharfe V, Schumacher R, Weigel H, Weinmann G, Zintl F, Hermann J |
Improved results in the treatment of acute myeloid leukemia - Results of study AML-BFM-93 in East Germany with comparisons to the preceding studies AML-I-82 and AML-II-87. |
Klin Pädiatr 2001, 213: 162 |
|
| Steinbach D, Hermann J, Littlewood T, Zintl F |
Risk group definition in children with acute myeloid leukemia by calculating individual risk factors on the basis of a multivariate stepwise Cox regression analysis. |
Leuk Lymphoma 2001, 42: 1289 |
|
| Steliarova-Foucher E, Berrino F, Coebergh J, Kaatsch P, Lacour B, Michaelis J, Mitlon N, Stiller C, Parkin D |
ACCISpass 1. 01, software for analysis and presentation of data on incidence and survival of children and adolescents in Europe. |
European Network of Cancer Registries 2002 |
|
| Steliarova-Foucher E, Stiller C, Kaatsch P, Berrino F, Coebergh J, Lacour B, Parkin M |
Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since 1970s. |
Lancet 2004 |
|
| Steliarova-Foucher E, Stiller C, Lacour B, Kaatsch P |
International Classification of Childhood Cancer, third edition. [+] |
Cancer 2005, 103: 1457 |
|
| BACKGROUND: The third edition of the International Classification of Diseases for Oncology (ICD-O-3), which was published in 2000, introduced major changes in coding and classification of neoplasms, notably for leukemias and lymphomas, which are important groups of cancer types that occur in childhood. This necessitated a third revision of the 1996 International Classification of Childhood Cancer (ICCC-3). METHODS: The tumor categories for the ICCC-3 were designed to respect several principles: agreement with current international standards, integration of the entities defined by newly developed diagnostic techniques, continuity with previous childhood classifications, and exhaustiveness. RESULTS: The ICCC-3 classifies tumors coded according to the ICD-O-3 into 12 main groups, which are split further into 47 subgroups. These 2 levels of the ICCC-3 allow standardized comparisons of the broad categories of childhood neoplasms in continuity with the previous classifications. The 16 most heterogeneous subgroups are broken down further into 2-11 divisions to allow study of important entities or homogeneous collections of tumors characterized at the cytogenetic or molecular level. Some divisions may be combined across the higher-level categories, such as the B-cell neoplasms within leukemias and lymphomas. CONCLUSIONS: The ICCC-3 respects currently existing international standards and was designed for use in international, population-based, epidemiological studies and cancer registries. The use of an international classification system is especially important in the field of pediatric oncology, in which the low frequency of cases requires rigorous procedures to ensure data comparability. |
| Steliarova-Foucher E, Stiller C, Kaatsch P, Berrino F, Coebergh JW, ACCIS Scientific Committee |
Trends in childhood cancer incidence in Europe, 1970-99. |
Lancet 2005, 365: 2088 |
|
| Steffens J, Treiyer A, Calaminus G |
[Management of pediatric testicular tumors : diagnosis, therapy, and follow-up]. [+] |
Der Urologe. Ausg. A 2009, 48: 359 |
|
| Based on findings from the Prepubertal Testis Tumor Registry by the Urologic Section of the American Academy of Pediatrics and collaborative data in the literature, a modern algorithm for the surgical management of prepubertal testis tumors is presented. Following testicular surgery, patients with universally benign tumors, such as teratoma, may be released from oncological follow-up. Children with stage I yolk sac tumors should be monitored closely with periodic AFP tumor marker evaluation and imaging according to the primary dissemination (e.g., ultrasound, chest x-ray, and computed tomography). Patients with recurrent or metastatic yolk sac tumors should be treated with platinum-based chemotherapy and appropriate follow-up. Retroperitoneal lymph node dissection is not recommended except for patients with residual retroperitoneal masses following chemotherapy. Aggressive treatment is warranted for metastatic Sertoli cell and metastatic undifferentiated stromal tumors. |
| Stegmaier S, Poremba C, Schaefer KL, Leuschner I, Kazanowska B, Békássy AN, Bielack SS, Klingebiel T, Koscielniak E |
Prognostic value of PAX-FKHR fusion status in alveolar rhabdomyosarcoma: A report from the cooperative soft tissue sarcoma study group (CWS). [+] |
Pediatr Blood Cancer 2011, 57: 406 |
|
| BACKGROUND: Alveolar Rhabdomyosarcomas (RMA) are characterized by chromosomal translocations, fusing the PAX3 or PAX7 gene with FKHR in about 85%. Previous studies have suggested that the fusion type is associated with prognosis. In order to investigate the predictive value of the PAX-FKHR fusion status on disease outcome of patients with RMA treated in the CWS trials we performed a retrospective analysis.
PROCEDURE: Between 1986 and 2004, out of 446 patients with RMA treated in four consecutive CWS trials, tumor samples from 126 patients were available for RT-PCR analysis. Survival depending on fusion status in context with known clinical risk-factors was analyzed.
RESULTS: Out of 126 samples, 121 had adequate quality for PAX-FKHR fusion status analysis. PAX-FKHR fusions were detected in 101 samples: 60% PAX3-FKHR and 24% PAX7-FKHR fusions, 17% were fusion-negative. There was no significant difference in survival between patients with PAX3-FKHR versus PAX7-FKHR positive tumors. The fusion transcript negative cohort showed a more favorable outcome than the fusion transcript positive cohort among patients with metastatic disease. From the established clinical risk-factors none was associated with a significantly higher risk of failure or death in a multivariate analysis.
CONCLUSIONS: PAX-FKHR fusion type was not a significant predictor for survival in our analysis. More extensive molecular analyses are needed to identify features with prognostic relevance and useful therapeutic impact. Pediatr Blood Cancer © 2011 Wiley-Liss, Inc. |
| Steinbach D, Wilhelm B, Kiermaier HR, Creutzig U, Schrappe M, Zimmermann M, Debatin KM, Gruhn B, von Stackelberg A, Jürgens H, Strahm B, Reinhardt D, Möricke A |
35. Long term survival in children with acute leukaemia and complications requiring mechanical ventilation. [+] |
Arch Dis Child 2011, [Epub ahead of print] |
|
| Objective Previous reports have indicated that the short term prognosis for patients with malignant diseases and serious adverse events requiring mechanical ventilation (SAEV) is improving. The purpose of this study was to determine whether these patients can be cured of malignant disease or whether they survive SAEV only to subsequently relapse. Patients and methods The authors report the outcome of children with SAEV treated in the multicentre studies ALL-BFM 95 and AML-BFM 98. Data from 1182 patients with acute lymphoblastic leukaemia (ALL) and 334 patients with acute myeloid leukaemia (AML) were analysed. 88 patients (51 ALL and 37 AML) developed SAEV. Results The prognosis was almost identical in ALL and AML patients (survival of SAEV patients: 48%, 95% CI 38% to 58%; overall survival after 5 years: 31%, 95% CI 21% to 41%). Prognosis was independent of the time between leukaemia diagnosis and SAEV. Approximately 20% of children who required haemodialysis (n=14) or cardiac resuscitation (n=16) achieved long term survival, but no patient who fulfilled more than three of six identified risk factors (age ≥10 years, high risk leukaemia, C reactive protein ≥150 mg/l, administration of inotropic infusion, cardiac resuscitation and haemodialysis) survived (n=16; 0%, 95% CI 0% to 20%). Conclusions Intensive care improves the short and long term survival of children with leukaemia. 64% (95% CI 50% to 78%) of children with acute leukaemia who survived SAEV achieved long term survival. Prognosis mainly depends on age and leukaemia risk group. |
| Stiller CA, Nectoux J |
International incidence of childhood brain and spinal tumours. |
Int J Epidemiol 1994, 23: 458 |
|
| Stöhr M, Brandt T, Einhäupl KM (Hrsg) |
Neurologische Syndrome in der Intensivmedizin. Differentialdiagnose und Akuttherapie. |
Kohlhammer Verlag 1190 |
|
| Stohr W, Langer T, Kremers A, Brecht I, Treuner J, Dinnesen A, Beck J |
Hearing function in soft tissue sarcoma patients after treatment with carboplatin. |
Oncology Reports 2004, 12: 767 |
|
| Stohr W, Langer T, Kremers A, Bielack S, Lamprecht-Dinnesen A, Frey E, Beck JD, German Late Effects Working Group in the German Society of Pediatric Oncology and Hematology |
Cisplatin-induced ototoxicity in osteosarcoma patients: a report from the late effects surveillance system. [+] |
Cancer investigation 2005, 23: 201 |
|
| The aim of this study was to analyze cisplatin-induced ototoxicity in a recent study trial. Seventy-four patients who had received cisplatin for the treatment of osteosarcoma (median cumulative dose: 360 mg/m2) were investigated prospectively for ototoxicity in a multicenter trial. Hearing function was tested by audiometry. We evaluated the incidence and dependencies of hearing loss. After cessation of therapy, 51% of the patients showed a hearing loss of >20 dB in the frequency range of 4-8 kHz. Only in one patient a hearing loss was found at 2 kHz, and in none at 1 kHz. At a cumulative cisplatin dose of < or = 240 mg/m2, almost no ototoxicity was found. Incidence and magnitude of hearing loss increased significantly with a higher cumulative dose. Furthermore, hearing thresholds were significantly poorer in children <12 years. A further follow-up investigation showed only a marginal change in hearing function. We conclude that ototoxicity is moderate in our group of patients and probably irreversible. |
| Stohr W, Paulides M, Brecht I, Kremers A, Treuner J, Langer T, Beck JD |
Comparison of epirubicin and doxorubicin cardiotoxicity in children and adolescents treated within the German Cooperative Soft Tissue Sarcoma Study (CWS). [+] |
Journal of cancer research and clinical oncology 2006, 132: 35 |
|
| Purpose: Up to now, cardiotoxicity of epirubicin has been studied almost exclusively in adult cancer patients. The aim of this study was to investigate epirubicin in children and adolescents, in comparison with doxorubicin. Methods: About 172 soft tissue sarcoma patients (mean age at diagnosis: 8.3 years), treated with epirubicin (median cumulative dose: 450 mg/m(2)) or doxorubicin (median cumulative dose: 240 mg/m(2)) within the high-risk group of the CWS-96 study, were examined in a prospective multicentre study. Heart function was analysed by echocardiography, measuring left-ventricular fractional shortening (FS). The median follow up was 27.7 months. Results: Incidence of clinically manifest cardiomyopathy was 0% (0/60; 95% CI: 0-6.0%) in patients treated with epirubicin, and 0.9% (1/108; 95% CI: 0-5.1%) in patients treated with doxorubicin. A further three patients showed subclinical cardiomyopathy. There was no difference in FS between the two treatment arms. Conclusions: Cardiotoxicity was low in our study. For the short term, cardiotoxicity seems to be only a minor problem in patients treated with epirubicin as applied in this cohort. |
| Stöhr W, Paulides M, Bielack S, Jürgens H, Treuner J, Rossi R, Langer T, Beck JD |
Ifosfamide-induced nephrotoxicity in 593 sarcoma patients: a report from the Late Effects Surveillance System. [+] |
Pediatric blood & cancer 2007, 48: 447 |
|
| BACKGROUND: Ifosfamide is widely used in paediatric oncology, but its use is limited by nephrotoxic side effects. The aim of this study was to evaluate the incidence and risk factors of tubulopathy, with special emphasis on the influence of age, where different findings have been published so far. PROCEDURE: Five hundred ninety three children and adolescents treated for Ewing, osteo- or soft-tissue sarcoma (median age at diagnosis: 11.7 years) were prospectively investigated for nephrotoxicity in the Late Effects Surveillance System (LESS) study. Tubulopathy was diagnosed in case of continuing hypophosphatemia and proteinuria. RESULTS: After a median follow up of 19 months, 27 patients (4.6%; 95% CI: 3.0-6.6%) had newly developed tubulopathy. This incidence was 0.4% (95% CI: 0-2.4%) in patients treated with a cumulative ifosfamide dose of < or =24 g/m2, 6.5% (95% CI: 3.6-10.7%) after 24-60 g/m2, and 8.0% (95% CI: 4.2-13.6%) after > or = 60 g/m2. In multivariate analysis, children younger than 4 years at time of diagnosis had an 8.7-fold (95% CI: 3.5-21.8) higher risk for tubulopathy than older patients. Neither carboplatin treatment nor abdominal irradiation showed any significant influence. CONCLUSION: Ifosfamide-induced nephrotoxicity was found in 4.6% of patients. Risk factors were the cumulative ifosfamide dose and young age at treatment. |
| Stöhr W, Paulides M, Bielack S, Jürgens H, Koscielniak E, Rossi R, Langer T, Beck JD |
Nephrotoxicity of cisplatin and carboplatin in sarcoma patients: a report from the late effects surveillance system. [+] |
Pediatric blood & cancer 2007, 48: 140 |
|
| BACKGROUND: Cisplatin and carboplatin are both nephrotoxic and can induce, to a different degree, impairment in glomerular function and hypomagnesemia. Prospective longitudinal studies on these renal impairments are rare in children and adolescents. PROCEDURE: Six hundred and fifty one sarcoma patients were investigated prospectively for nephrotoxicity in the Late Effects Surveillance System (LESS) network (median follow-up 2 years). Median cumulative dose was 360 mg/m(2) for cisplatin, and 1,500 mg/m(2) for carboplatin. Patients not treated with any platinum derivative were used as controls. Most patients (including controls) also received ifosfamide. Renal function was tested by serum magnesium, serum creatinine, and the GFR as estimated by the Schwartz formula. We evaluated incidence, dependencies, and the course of impairments. RESULTS: There was no observed platinum-induced reduction of glomerular function over time. After cessation of antineoplastic therapy, hypomagnesemia (<0.7 mmol/L) occurred in 12.1% (95% CI: 6.8%-19.4%) of patients after cisplatin therapy, and in 15.6% (95% CI: 5.3%-32.8%) after carboplatin therapy, in comparison with 4.5% (95% CI: 2.0%-8.7%) in patients without any treatment with platinum derivatives (P = 0.008). In all groups, the frequency of hypomagnesemia decreased with ongoing follow-up, but serum magnesium remained lower in platinum treated patients throughout the study period. CONCLUSION: Nephrotoxicity after treatment with cisplatin and carboplatin was mild in our study. Further studies have to show if serum magnesium is permanently decreased in platinum treated patients and if this will result in any clinically relevant impairment. |
| Stoepker C, Hain K, Schuster B, Hilhorst-Hofstee Y, Rooimans MA, Steltenpool J, Oostra AB, Eirich K, Korthof ET, Nieuwint AW, Jaspers NG, Bettecken T, Joenje H, Schindler D, Rouse J, de Winter JP |
SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype. [+] |
Nat Genet 2011, 43: 138 |
|
| DNA interstrand crosslink repair requires several classes of proteins, including structure-specific endonucleases and Fanconi anemia proteins. SLX4, which coordinates three separate endonucleases, was recently recognized as an important regulator of DNA repair. Here we report the first human individuals found to have biallelic mutations in SLX4. These individuals, who were previously diagnosed as having Fanconi anemia, add SLX4 as an essential component to the FA-BRCA genome maintenance pathway. |
| Strother D, Ashley D, Kellie SJ, Patel A, Jones-Wallace D, Thompson S, Heideman R, Benaim E, Krance R, Bowman L, Gajjar A |
Feasibility of four consecutive high-dose chemotherapy cycles with stem-cell rescue for patients with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor after craniospinal radiotherapy: results of a collaborative study. [+] |
J Clin Oncol 2001, 19: 2696 |
|
| PURPOSE: This study was designed to determine the feasibility and safety of delivering four consecutive cycles of high-dose cyclophosphamide, cisplatin, and vincristine, each followed by stem-cell rescue, every 4 weeks, after completion of risk-adapted craniospinal irradiation to children with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor (PNET). PATIENTS AND METHODS: Fifty-three patients, 19 with high-risk disease and 34 with average-risk disease, were enrolled onto this study. After surgical resection, high-risk patients were treated with topotecan in a 6-week phase II window followed by craniospinal radiation therapy and four cycles of high-dose cyclophosphamide (4,000 mg/m2 per cycle), with cisplatin (75 mg/m2 per cycle), and vincristine (two 1.5-mg/m2 doses per cycle). Support with peripheral blood stem cells or bone marrow and with granulocyte colony-stimulating factor was administered after each cycle of high-dose chemotherapy. Treatment of average-risk patients consisted of surgical resection and craniospinal irradiation, followed by the same chemotherapy given to patients with high-risk disease. The expected duration of the chemotherapy was 16 weeks, with a cumulative cyclophosphamide dose of 16,000 mg/m2 and a planned dose-intensity of 1,000 mg/m2/wk. RESULTS: Fifty of the 53 patients commenced high-dose chemotherapy, and 49 patients completed all four cycles. The median length of chemotherapy cycles one through four was 28, 27, 29, and 28 days, respectively. Engraftment occurred at a median of 14 to 15 days after infusion of stem cells or autologous bone marrow. The intended dose-intensity of cyclophosphamide was 1,000 mg/m2/wk; the median delivered dose-intensity was 1,014, 1,023, 974, and 991 mg/m2/wk for cycles 1 through 4, respectively; associated median relative dose-intensity was 101%, 102%, 97%, and 99%. No deaths were attributable to the toxic effects of high-dose chemotherapy. Early outcome analysis indicates a 2-year progression-free survival of 93.6% +/- 4.7% for the average-risk patients. For the high-risk patients, the 2-year progression-free survival is 73.7% +/- 10.5% from the start of therapy and 84.2% +/- 8.6% from the start of radiation therapy. CONCLUSION: Administering four consecutive cycles of high-dose chemotherapy with stem-cell support after surgical resection and craniospinal irradiation is feasible in newly diagnosed patients with medulloblastoma/supratentorial PNET with aggressive supportive care. The early outcome results of this approach are very encouraging |
| Strahm B, Nöllke P, Zecca M, Korthof ET, Bierings M, Furlan I, Sedlacek P, Chybicka A, Schmugge M, Bordon V, Peters C, O'Marcaigh A, de Heredia CD, Bergstraesser E, Moerloose BD, van den Heuvel-Eibrink MM, Starý J, Trebo M, Wojcik D, Niemeyer CM, Locatelli F, EWOG-MDS study group |
Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. [+] |
Leukemia 2011, 25: 455 |
|
| We report on the outcome of children with advanced primary myelodysplastic syndrome (MDS) transplanted from an HLA-matched sibling (MSD) or an unrelated donor (UD) following a preparative regimen with busulfan, cyclophosphamide and melphalan. Ninety-seven patients with refractory anemia with excess blasts (RAEB, n=53), RAEB in transformation (RAEB-T, n=29) and myelodysplasia-related acute myeloid leukemia (MDR-AML, n=15) enrolled in the European Working Group of MDS in Childhood (EWOG-MDS) 98 study and given hematopoietic stem cell transplantation (HSCT) were analyzed. Median age at HSCT was 11.1 years (range 1.4-19.0). Thirty-nine children were transplanted from an MSD, whereas 58 were given the allograft from a UD (n=57) or alternative family donor (n=1). Stem cell source was bone marrow (n=69) or peripheral blood (n=28). With a median follow-up of 3.9 years (range 0.1-10.9), the 5-year probability of overall survival is 63%, while the 5-year cumulative incidence of transplantation-related mortality (TRM) and relapse is 21% each. Age at HSCT greater than 12 years, interval between diagnosis and HSCT longer than 4 months, and occurrence of acute or extensive chronic graft-versus-host disease were associated with increased TRM. The risk of relapse increased with more advanced disease. This study indicates that HSCT following a myeloablative preparative regimen offers a high probability of survival for children with advanced MDS. |
| Strahm B, Nöllke P, Zecca M, Korthof ET, Bierings M, Furlan I, Sedlacek P, Chybicka A, Schmugge M, Bordon V, Peters C, O'Marcaigh A, de Heredia CD, Bergstraesser E, Moerloose BD, van den Heuvel-Eibrink MM, Starý J, Trebo M, Wojcik D, Niemeyer CM, Locatelli F, EWOG-MDS study group |
Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. [+] |
Leukemia 2011, 25: 455 |
|
| We report on the outcome of children with advanced primary myelodysplastic syndrome (MDS) transplanted from an HLA-matched sibling (MSD) or an unrelated donor (UD) following a preparative regimen with busulfan, cyclophosphamide and melphalan. Ninety-seven patients with refractory anemia with excess blasts (RAEB, n=53), RAEB in transformation (RAEB-T, n=29) and myelodysplasia-related acute myeloid leukemia (MDR-AML, n=15) enrolled in the European Working Group of MDS in Childhood (EWOG-MDS) 98 study and given hematopoietic stem cell transplantation (HSCT) were analyzed. Median age at HSCT was 11.1 years (range 1.4-19.0). Thirty-nine children were transplanted from an MSD, whereas 58 were given the allograft from a UD (n=57) or alternative family donor (n=1). Stem cell source was bone marrow (n=69) or peripheral blood (n=28). With a median follow-up of 3.9 years (range 0.1-10.9), the 5-year probability of overall survival is 63%, while the 5-year cumulative incidence of transplantation-related mortality (TRM) and relapse is 21% each. Age at HSCT greater than 12 years, interval between diagnosis and HSCT longer than 4 months, and occurrence of acute or extensive chronic graft-versus-host disease were associated with increased TRM. The risk of relapse increased with more advanced disease. This study indicates that HSCT following a myeloablative preparative regimen offers a high probability of survival for children with advanced MDS. |
| Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group |
Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. |
N Engl J Med 2005, 352: 987 |
|
| Stutterheim J, Gerritsen A, Zappeij-Kannegieter L, Kleijn I, Dee R, Hooft L, van Noesel MM, Bierings M, Berthold F, Versteeg R, Caron HN, van der Schoot CE, Tytgat GA |
PHOX2B is a novel and specific marker for minimal residual disease testing in neuroblastoma. [+] |
Journal of clinical oncology 2008, 26: 5443 |
|
| PURPOSE: Polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) in neuroblastoma can be used to monitor therapy response and to evaluate stem cell harvests. Commonly used PCR markers, tyrosine hydroxylase (TH) and GD2 synthase, have expression in normal tissues, thus limiting MRD detection. To identify a more specific MRD marker, we tested PHOX2B. PATIENTS AND METHODS: To determine PHOX2B, TH, and GD2 synthase expression in normal tissues, it was measured by real-time quantitative PCR in samples of normal bone marrow (BM; n = 51), peripheral blood (PB; n = 37), and peripheral-blood stem cells (PBSCs; n = 24). Then, 289 samples of 101 Dutch patients and 47 samples of 43 German patients were tested for PHOX2B and TH; these samples included 52 tumor, 214 BM, 32 BM, and 38 PBSC harvests. Of the 214 BM samples, 167 were compared with cytology, and 47 BM samples were compared with immunocytology (IC). RESULTS: In contrast to TH and GD2 synthase, PHOX2B was not expressed in any of the normal samples. In patient samples, PHOX2B was detected in 32% cytology-negative and in 14% IC-negative samples and in 94% of cytology-positive and in 90% of IC-positive BM samples. Overall, PHOX2B was positive in 43% compared with 31% for TH. In 24% of all samples, TH expression was inconclusive, which is similar to expression found in normal tissues. In 42% of these samples, PHOX2B expression was positive. CONCLUSION: PHOX2B is superior to TH and GD2 synthase in specificity and sensitivity for MRD detection of neuroblastoma by using real-time quantitative PCR. We propose to include PHOX2B in additional prospective MRD studies in neuroblastoma alongside TH and other MRD markers. |
| Stutterheim J, Gerritsen A, Zappeij-Kannegieter L, Yalcin B, Dee R, van Noesel MM, Berthold F, Versteeg R, Caron HN, van der Schoot CE, Tytgat GA |
Detecting minimal residual disease in neuroblastoma: the superiority of a panel of real-time quantitative PCR markers. [+] |
Clinical chemistry 2009, 55: 1316 |
|
| BACKGROUND: PCR-based detection of minimal residual disease (MRD) in neuroblastoma (NB) patients can be used for initial staging and monitoring therapy response in bone marrow (BM) and peripheral blood (PB). PHOX2B has been identified as a sensitive and specific MRD marker; however, its expression varies between tumors. Therefore, a panel of markers could increase sensitivity. METHODS: To identify additional MRD markers for NB, we selected genes by comparing SAGE (serial analysis of gene expression) libraries of healthy and NB tissues followed by extensive real-time quantitative PCR (RQ-PCR) testing in samples of tumors (n = 56), control BM (n = 51), PB (n = 37), and cell subsets. The additional value of a panel was determined in 222 NB samples from 82 Dutch stage 4 NB patients (54 diagnosis BM samples, 143 BM samples during/after treatment, and 25 PB samples). RESULTS: We identified 2 panels of specific RQ-PCR markers for MRD detection in NB patients: 1 for analysis of BM samples (PHOX2B, TH, DDC, CHRNA3, and GAP43) and 1 for analysis of PB samples (PHOX2B, TH, DDC, DBH, and CHRNA3). These markers all showed high expression in NB tumors and no or low expression in control BM or PB samples. In patients' samples, the PHOX2B marker detected most positive samples. In PB samples, however, 3 of 7 PHOX2B-negative samples were positive for 1 or more markers, and in BM examinations during treatment, 7% (6 of 86) of the PHOX2B-negative samples were positive for another marker. CONCLUSIONS: Because of differences in the sensitivities of the markers in BM and PB, we advise the use of 2 different panels to detect MRD in these compartments. |
| Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C, Pfaff E, Tönjes M, Sill M, Bender S, Kool M, Zapatka M, Becker N, Zucknick M, Hielscher T, Liu XY, Fontebasso AM, Ryzhova M, Albrecht S, Jacob K, Wolter M, Ebinger M, Schuhmann MU, van Meter T, Frühwald MC, Hauch H, Pekrun A, Radlwimmer B, Niehues T, von Komorowski G, Dürken M, Kulozik AE, Madden J, Donson A, Foreman NK, Drissi R, Fouladi M, Scheurlen W, von Deimling A, Monoranu C, Roggendorf W, Herold-Mende C, Unterberg A, Kramm CM, Felsberg J, Hartmann C, Wiestler B, Wick W, Milde T, Witt O, Lindroth AM, Schwartzentruber J, Faury D, Fleming A, Zakrzewska M, Liberski PP, Zakrzewski K, Hauser P, Garami M, Klekner A, Bognar L, Morrissy S, Cavalli F, Taylor MD, van Sluis P, Koster J, Versteeg R, Volckmann R, Mikkelsen T, Aldape K, Reifenberger G, Collins VP, Majewski J, Korshunov A, Lichter P, Plass C, Jabado N, Pfister SM |
Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. [+] |
Cancer cell 2012, 22: 425 |
|
| Glioblastoma (GBM) is a brain tumor that carries a dismal prognosis and displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical amino acids (K27 and G34) of histone H3.3 in one-third of pediatric GBM. Here, we show that each H3F3A mutation defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and that they are mutually exclusive with IDH1 mutations, which characterize a third mutation-defined subgroup. Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM and/or established transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of transcription factors OLIG1, OLIG2, and FOXG1, possibly reflecting different cellular origins. |
| Stöhr W, Langer T, Kremers A, Bielack S, Dinnesen A, Frey E, Beck J |
Cisplatin-induced Ototoxicity in Osteosarcoma Patients. |
Cancer Investigation 2004,in press |
|
| Subbiah V, Ketonen L, Bruner JM, Nunez R, Weinberg J, Wolff JE |
99mTc-sestamibi scan differentiates tumor from other contrast enhancing tissue in choroid plexus tumors. [+] |
J Clin Onco 2010, 32: 160 |
|
| Choroid plexus tumors are rare brain tumors which account for 0.4% to 0.6% among brain tumors. Tumor resection is known to be of large prognostic impact, and re-resection of residual tumors is a part of standard care. However, after multiple resections it can become difficult to differentiate tumor from reactive tissue. 99mTC-sestamibi scans may assist in differentiating neoplastic (99mTC-sestamibi positive) from non-neoplastic tissue (99mTC-sestamibi negative). Previous literature showed sestamibi to be helpful in detecting residual choroid plexus tumors resulting in further resection. Here, we report the first case to show that sestamibi scans can also help with the opposite decision. |
| Sudbrock F, Schmidt M, Simon T, Eschner W, Berthold F, Schicha H |
Dosimetry for (131)I-MIBG therapies in metastatic neuroblastoma, phaeochromocytoma and paraganglioma. [+] |
European journal of nuclear medicine and molecular imaging 2010, |
|
| PURPOSE: Radiation dosimetry is a basic requirement for targeted radionuclide therapies (TRT) which have become of increasing interest in nuclear medicine. Despite the significant role of the radiopharmaceutical (131)I-metaiodobenzylguanidine (MIBG) for the treatment of metastatic neuroblastoma, phaeochromocytoma and paraganglioma details for a reliable dosimetry are still sparse. This work presents our procedures, the dosimetric data and experiences with TRT using (131)I-MIBG. METHODS: A total of 21 patients were treated with (131)I-MIBG between 2004 and 2008 according to a clearly defined protocol. Whole-body absorbed doses were determined by a series of scintillation probe readings for all 21 cases. Tumour absorbed doses were calculated on the basis of quantitative imaging for an entity of 25 lesions investigated individually using the region of interest (ROI) technique based on five scans each. RESULTS: Typical whole-body absorbed doses are found in the region of 2 Gy (range: 1.0-2.9 Gy) whereas tumour absorbed doses in turn cover a span between 10 and 60 Gy. Nonetheless this variation of tumour absorbed doses is comparatively low. CONCLUSION: The trial protocol in use is a substantial advancement in terms of reliable dosimetry. A clearly defined modus operandi for MIBG therapies should involve precisely described dosimetric procedures, e.g. a minimum of 20 whole-body measurements using a calibrated counter and at least four gamma camera scans over the whole period of the inpatient stay should be carried out. Calculation of tumour volumes is accomplished best via evaluation of SPECT and CT images. |
| Surico G, Muggeo P, Rigillo N, Gadner H |
Concurrent Langerhans cell histiocytosis and myelodysplasia in children. |
Med Pediatr Oncol 2000, 35: 421 |
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| Sutor A, Niemeyer C, Sauter S, Witt I, Kaufmehl K, Rombach A, Brandis M, Riehm H |
Changes in blood coagulation in treatment with ALL-BFM-90 and NHL-BFM-90 protocols. |
Klin Pädiatr 1992, 204: 264 |
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| Sutton LN, Molloy PT, Sernyak H, Goldwein J, Phillips PL, Rorke LB, Moshang T Jr, Lange B, Packer RJ |
Long-term outcome of hypothalamic/chiasmatic astrocytomas in children treated with conservative surgery. |
J Neurosurg 1995, 83: 583 |
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| Suttorp M, Millot F |
Treatment of pediatric chronic myeloid leukemia in the year 2010: use of tyrosine kinase inhibitors and stem-cell transplantation. [+] |
Hematology 2010, 368 |
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| Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the only proven cure for chronic myeloid leukemia (CML), a rare malignancy in childhood. With the excellent results induced by the tyrosine kinase inhibitor (TKI) imatinib in adults in the last decade, the appropriate management of children with CML has also changed radically, and only a minority are now transplanted as a front-line treatment. Data on pediatric experiences with imatinib in CML from controlled trials remain very limited, but this review of available data describes the role of imatinib in children with CML, addressing: 1) the starting dose; 2) pharmacokinetics in childhood; 3) possible adverse effects, with a focus on the still-growing skeleton; 4) early monitoring of treatment efficacy in an attempt to avoid failure; 5) the timing of allo-SCT in children; and 6) treatment of CML relapse after allo-SCT. Because the characteristics of CML in children seem to overlap extensively with what is described in adult internal medicine, most answers and pediatric algorithms are adapted from the treatment of CML in adults. Today in 2010, allo-SCT in children should be postponed until CML becomes refractory to imatinib. The approach for young patients with suboptimal responses is unclear because data on the efficacy and safety of second-generation TKIs in childhood are almost entirely missing. Other than being included in a formal trial on second-generation TKIs, allo-SCT for patients failing imatinib remains the first choice. |
| Suttorp M, Yaniv I, Schultz KR |
Controversies in the treatment of CML in children and adolescents: TKIs versus BMT? [+] |
Biology of blood and marrow transplantation 2011, 17(1 Suppl):S115 |
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| Chronic myeloid leukemia (CML) is a relatively rare hematopoietic malignancy in the pediatric and adolescent population. This makes it difficult to perform clinic trials that can define the best therapeutic option when considering the impact of tyrosine kinase inhibitors (TKIs) versus the established approach of allogeneic hematopoietic cell transplantation (HCT). With the relatively low toxicity of TKIs, there are little data regarding when HCT or long-term TKI therapy is a better option. There are even less data regarding the duration of TKI treatment in the pediatric CML in chronic phase (CML-CP) patients who may receive over 60 years of therapy. As children and adolescent are treated for longer times with TKIs, it has become clear that toxicities may make long-term TKI therapy less attractive compared to allogeneic HCT. HCT has the long-term complications of growth failure, infertility, chronic graft-versus-host disease (GVHD), metabolic syndrome, and secondary malignancies, whereas prolonged TKIs may cause growth failure, hepatic, and cardiac complications. Moreover, HCT is a potentially curative intervention, whereas TKI is not curative, requiring prolonged exposure. In this article, we discuss the relative merit of the 2 therapeutic approaches and recommend that all children and adolescents with CML-CP should initially be treated with imatinib and maintained with TKI therapy indefinitely if there is a good response. We recommend that allogeneic HCT with an HLA-identical sibling donor or closely matched unrelated donor be considered for patients with treatment failure or recurrence after receiving salvage second-generation TKI treatment. We also conclude that randomized international trials are urgently needed to evaluate the best therapies for pediatric CML. |
| Suttorp M, Eckardt L, Tauer JT, Millot F |
Management of chronic myeloid leukemia in childhood. [+] |
Current hematologic malignancy reports 2012, 7: 116 |
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| Childhood chronic myelogenous leukemia (CML) is a rare malignancy, and experience with optimal treatment is very limited. Traditionally, allogeneic hematopoietic stem cell transplantation was considered the only curative treatment. Imatinib, a small-molecule inhibitor of the BCR-ABL tyrosine kinase (TKI), has been proven highly successful in adults with CML, resulting in prolonged molecular response with limited drug toxicity. This drug is now included as front-line therapy for CML in pediatrics as well, though valid concerns about serious late sequelae remain unresolved. Specific pediatric treatment guidelines have not yet been formulated, and most algorithms are derived from experience in adult CML. This overview attempts to summarize pediatric studies on issues such as dose, duration, adverse effects, and steering criteria for TKI treatment, adapting guidelines developed in adult medicine to pediatrics. Most importantly, pediatric patients with CML receiving TKI treatment should be enrolled into formal trials. |
| Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (Eds) |
WHO Classification of Tumours of the Haematopoetic and Lymphoid Tissues. |
Lyon, France: IARC Press 2008, 109 |
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| Sykora K, Tomeczkowski J, Kirchhoff K, Yakisan E, Reiter A, Welte K |
Growth inhibition of IL-7 receptor positiv childhood Burkitt's lymphoma cells is due to induction of apoptosis. |
Molecular Biology of Hematopoiesis 1996, 191 |
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| Sykora K, Tomeczkowski J, Reiter A |
C-kit receptors in childhood malignant lymphoblastic cells. |
Leuk Lymphoma 1997, 25: 201 |
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| Szavay P, Luithle T, Semler O, Graf N, Fuchs J |
Surgery of cavoatrial tumor thrombus in nephroblastoma. |
Pediatr Blood Cancer 2004, 43: 40 |
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| Szczepański T, van der Velden VHJ, Waanders E, Kuiper RP, Van Vlierberghe P, Gruhn B, Eckert C, Panzer-Grümayer R, Basso G, Cavé H, zur Stadt U, Campana D, Schrauder A, Sutton R, van Wering E, Meijerink JPP, van Dongen JJM |
Late Recurrence of Childhood T-Cell Acute Lymphoblastic Leukemia Frequently Represents a Second Leukemia Rather Than a Relapse: First Evidence for Genetic Predisposition. |
Journal of Clinical Oncology 2011, 1643 |
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