| Autor(en) |
Titel |
Quelle |
Links |
| Bader P, Beck J, Frey A, Schlegel P, Hebarth H, Handgretinger R, Einsele H, Niemeyer C, Benda N, Faul C, Kanz L, Niethammer D, Klingebiel T |
Serial and quantitive analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogenic BMT. |
Bone Marrow Transplant 1998, 21: 487 |
  |
| Bader P, Stoll K, Huber S, Geiselhart A, Handgretinger R, Niemeyer C, Einsele H, Schlegel PG, Niethammer D, Beck J, Klingebiel T |
Characterization of lineage-specific chimaerism in patients with acute leukaemia and myelodysplastic syndrome after allogeneic stem cell transplantation before and after relapse. [+] |
British journal of haematology 2000, 108: 761 |
|
| Recently, we have shown that patients with acute leukaemias and myelodysplastic syndromes (MDS), who showed increasing mixed chimaerism (MC) upon serial PCR analysis after transplant, have a significantly increased risk of relapse. To determine whether the increasing MC in these patients is caused by the reappearance of normal recipient haematopoiesis or by the reoccurrence of malignant cells, we purified different leucocyte subpopulations and analysed these subfractions with regard to their donor-recipient ratio by a PCR-based method for the analysis of minisatellite DNA regions. In 14 patients [eight acute lymphoblastic leukaemia (ALL), three acute myelogenous leukaemia (AML) and three MDS] subfractions were analysed when increasing MC was first noted upon serial analysis of the peripheral blood. In seven of these 14 patients (four ALL, two AML and one MDS), subfractions were characterized at the time of frank haematological relapse. In all 14 patients investigated with increasing MC, recipient cells were detected in different mononuclear cell subpopulations. In patients characterized during frank relapse, two distinct distribution patterns were found. Patients who relapsed before day +300 (one ALL, two AML and one MDS) showed recipient-derived (normal) cells in addition to blast populations in different mononuclear subsets as well as granulocytes. In patients with acute leukaemias who relapsed after day +300 (two ALL and one AML), only leukaemic cells were found that were of recipient origin, whereas all other haematopoietic cell lines were donor derived. These data show that persistent MC in the early post-transplant period is caused predominantly by normal recipient haematopoietic cells. This finding further supports the hypothesis that a state of mixed haematopoietic chimaerism may reduce the clinical graft-versus-leukaemia (GVL) effect of alloreactive donor-derived effector cells in patients with acute leukaemias and MDS, and thus facilitate the proliferation of residual malignant cells that may have survived the preparative regimen. |
| Bader P, Kreyenberg H, Hoelle W, Dueckers G, Handgretinger R, Lang P, Kremens B, Dilloo D, Sykora KW, Schrappe M, Niemeyer C, Von Stackelberg A, Gruhn B, Henze G, Greil J, Niethammer D, Dietz K, Beck JF, Klingebiel T |
Increasing mixed chimerism is an important prognostic factor for unfavorable outcome in children with acute lymphoblastic leukemia after allogeneic stem-cell transplantation. |
J Clin Oncol 2004, 22: 1696 |
|
| Bader P, Kreyenberg H, Hoelle W, Dueckers G, Kremens B, Dilloo D, Sykora K, Niemeyer C, Reinhardt D, Vormoor J, Gruhn B, Lang P, Greil J, Handgretinger R, Niethammer D, Klingebiel T, Beck J |
Increasing mixed chimerism defines a high-risk group of childhood acute myelogenous leukemia patients after allogeneic stem cell transplantation where pre-emptive immunotherapy may be effective. |
Bone Marrow Transplant 2004, 33: 815 |
|
| Bader P, Niemeyer C, Weber G, Coliva T, Rossi V, Kreyenberg H, Gerecke A, Biondi A |
WT1 gene expression: useful marker for minimal residual disease in childhood myelodysplastic syndromes and juvenile myelo-monocytic leukemia? [+] |
European journal of haematology 2004, 73: 25 |
|
| The WT1 gene is considered to be highly expressed in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia and chronic myeloid leukemia and is thought to play a key role in maintaining the viability of leukemia cells. However, little is known about the WT1 gene expression levels in pediatric patients with juvenile myelo-monocytic leukemia (JMML) and myelodysplastic syndromes (MDS). We studied WT1 expression in diagnostic bone marrow (BM) and peripheral blood (PB) samples of 90 patients with JMML, low grade MDS, advanced MDS and myelodysplasia-related AML in BM (n = 20) and PB (n = 18) samples of normal healthy volunteer donors. |
| Bader P, Niemeyer C, Willasch A, Kreyenberg H, Strahm B, Kremens B, Gruhn B, Dilloo D, Vormoor J, Lang P, Niethammer D, Klingebiel T, Beck JF |
Children with myelodysplastic syndrome (MDS) and increasing mixed chimaerism after allogeneic stem cell transplantation have a poor outcome which can be improved by pre-emptive immunotherapy. [+] |
British journal of haematology 2005, 128: 649 |
|
| We recently reported that virtually all children with acute leukaemia and myelodysplastic syndrome (MDS) who develop the phenotype of increasing mixed chimaerism (MC) after allogeneic stem cell transplantation (allo-SCT) will relapse. We therefore performed a prospective, multi-centre study focused on children with MDS (n = 65; advanced MDS = 44, refractory cytopenia = 21) after allo-SCT in order to determine to what extent relapse can be prevented by pre-emptive immunotherapy on the basis of increasing MC. Analyses of chimaerism in 44 patients with advanced MDS revealed 31 cases with complete chimaerism (CC)/low-level MC/transient MC, 11 cases with increasing MC and two cases with decreasing MC. The same analyses in 21 MDS patients with refractory cytopenia revealed 17 cases with CC/low-level MC, one case with increasing MC and three cases with decreasing MC. Pre-emptive immunotherapy performed on each patient that showed increasing MC improved event-free survival from 0%, as seen in prior studies, to 50%. We therefore conclude that pre-emptive immunotherapy is an effective treatment option to prevent impending relapse in children with MDS after allo-SCT. |
| Bader P, Kreyenberg H, Henze GH, Eckert C, Reising M, Willasch A, Barth A, Borkhardt A, Peters C, Handgretinger R, Sykora KW, Holter W, Kabisch H, Klingebiel T, von Stackelberg A, ALL-REZ BFM Study Group |
Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM Study Group. [+] |
Journal of clinical oncology 2009, 27: 377 |
|
| PURPOSE: Minimal residual disease (MRD) before allogeneic stem-cell transplantation was shown to predict outcome in children with relapsed acute lymphoblastic leukemia (ALL) in retrospective analysis. To verify this, the Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Münster (ALL-REZ BFM) Study Group conducted a prospective trial. PATIENTS AND METHODS: Between March 1999 and July 2005, 91 children with relapsed ALL treated according to the ALL-REZ BFM 96 or 2002 protocols and receiving stem-cell transplantation in >or= second remission were enrolled. MRD quantification was performed by real-time polymerase chain reaction using T-cell receptor and immunoglobulin gene rearrangements. RESULTS: Probability of event-free survival (pEFS) and cumulative incidence of relapse (CIR) in 45 patients with MRD >or= 10(-4) leukemic cells was 0.27 and 0.57 compared with 0.60 and 0.13 in 46 patients with MRD less than 10(-4) leukemic cells (EFS, P = .004; CIR, P < .001). Intermediate-risk patients (strategic group S1) with MRD >or= 10(-4) leukemic cells (n = 14) had a pEFS of 0.20 and CIR of 0.73, whereas patients with MRD less than 10(-4) leukemic cells (n = 21) had a pEFS of 0.68 and CIR of 0.09 (EFS, P = .020; CIR, P < .001). High-risk patients (S3/4, third complete remission) who received transplantation with an MRD load of less than 10(-4) leukemic cells (n = 25) showed a pEFS and CRI of 0.53 and 0.18, respectively. In contrast, pEFS and CRI were 0.30 and 0.50 in patients who received transplantation with an MRD load of >or= 10(-4) leukemic cells. Multivariate Cox regression analysis revealed MRD as the only independent parameter predictive for EFS (P = .006). CONCLUSION: MRD is an important predictor for post-transplantation outcome. As a result, new strategies with modified stem-cell transplantation procedures will be evaluated in ALL-BFM trials. |
| Baker KS, DeLaat CA, Steinbuch M, Gross TG, Shapiro RS, Loechelt B, Harris R, Filipovich AH |
Successful correction of hemophagocytic lymphohistiocytosis with related or unrelated bone marrow transplantation. [+] |
Blood 1997, 89: 3857 |
|
| Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune regulation leading to widespread lymphocytic and hemophagocytic infiltration of vital organs. Apparent cure has only been achieved with allogeneic bone marrow transplantation (BMT). This report describes 20 consecutive patients, who underwent either matched sibling donor (n = 4) or unrelated donor (URD; n = 16) BMT. Age at the time of BMT was 0.4 to 5.3 years (median, 0.8 years). Central nervous system disease was present at diagnosis in 13 patients. At BMT, 14 patients were in a clinical remission, whereas 6 patients had active HLH. All patients were engrafted after cytoreduction with busulfan, cyclophosphamide, and etoposide. The probability of grade II-III acute graft-versus-host disease (GVHD) for all patients was 57% (95% confidence limit [CL], 0.28, 0.86), and 73% (95% CL, 0.44, 1.0) in URD patients. The overall probability of survival at 3 years was 45% (95% CL, 0.23, 0.67) and 44% (95% CL, 0.19, 0.68) when URD BMT was evaluated separately. Favorable BMT outcome was associated with clinical remission status at the time of BMT. The preparative regimen was well tolerated, and in the 9 surviving patients it provided durable engraftment and was effective at eradicating the underlying disease. |
| Baker KS, DeFor TE, Burns LJ, Ramsay NK, Neglia JP, Robison LL |
New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. [+] |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2003 Apr 1; 21: 1352 |
|
| To determine the incidence and risk factors for the development of new malignancies occurring after stem-cell transplantation (SCT). |
| Balduzzi A, Valsecchi MG, Uderzo C, De Lorenzo P, Klingebiel T, Peters C, Stary J, Felice MS, Magyarosy E, Conter V, Reiter A, Messina C, Gadner H, Schrappe M |
Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. [+] |
Lancet 2005, 366: 635 |
|
| BACKGROUND: The dismal prognosis of very-high-risk childhood acute lymphoblastic leukaemia could be improved by allogeneic haemopoietic cell transplantation. We compared this strategy with intensified chemotherapy protocols, with the aim to improve the outcome of children with very-high-risk acute lymphoblastic leukaemia in first complete remission. METHODS: A cooperative prospective study was set up in seven countries. Very-high-risk acute lymphoblastic leukaemia in first complete remission was defined by the presence of at least one of the following criteria: (1) failure to achieve complete remission after the first four-drug induction phase; (2) t(9;22) or t(4;11) clonal abnormalities; and (3) poor response to prednisone associated with T immunophenotype, white-blood-cell count of 100x10(9)/L or greater, or both. Children were allocated treatment by genetic chance, according to the availability of a compatible related donor, and assigned chemotherapy or haemopoietic-cell transplantation. The primary outcome was disease-free survival and analysis was by intention to treat. FINDINGS: Between April, 1995, and December, 2000, 357 children entered the study, of whom 280 were assigned chemotherapy and 77 related-donor haemopoietic-cell transplantation. 5-year disease-free survival was 40.6% (SE 3.1) in children allocated chemotherapy and 56.7% (5.7) in those assigned transplantation (hazard ratio 0.67 [95% CI 0.46-0.99]; p=0.02); 5-year survival was 50.1% (3.1) and 56.4% (5.9), respectively (0.73 [0.49-1.09]; p=0.12). INTERPRETATION: Children with very-high-risk acute lymphoblastic leukaemia benefit from related-donor haemopoietic-cell transplantation compared with chemotherapy. The gap between the two strategies increases as the risk profile of the patient worsens. |
| Balmer A, Zografos L, Munier F |
Diagnosis and current management of retinoblastoma. [+] |
Oncogene 2006 Aug 28; 25: 5341 |
|
| Retinoblastoma represents the prototypic model for inherited cancers. The RB1 gene was the first tumor suppressor gene to be identified. It represents the most frequent primary eye cancer in children under 15 years old, habitually occurring in infancy, even in utero, but can be observed in older children or young adults. Many other retinal lesions may also simulate retinoblastoma. The two major presenting signs are leukocoria and strabismus, but other ocular or general signs may be observed. A highly malignant tumor, retinoblastoma can nowadays be cured. The heritable form, however, carries a high risk of second nonocular tumors. Treatment in the early stages of disease holds a good prognosis for survival and salvage of visual function. In very late stages, however, the prognosis for ocular function and even survival is jeopardized. |
| Balduzzi A, De Lorenzo P, Schrauder A, Conter V, Uderzo C, Peters C, Klingebiel T, Stary J, Felice MS, Magyarosy E, Schrappe M, Dini G, Gadner H, Valsecchi MG |
Eligibility for allogeneic transplantation in very high risk childhood acute lymphoblastic leukemia: the impact of the waiting time. [+] |
Haematologica 2008, 93: 925 |
|
| The advantage of allogeneic transplant from compatible related donors versus chemotherapy in children with very-high-risk acute lymphoblastic leukemia in first complete remission was previously demonstrated in an international prospective trial. This study quantified the impact of time elapsed in first remission in the same cohort. Of 357 pediatric patients with very-high-risk acute lymphoblastic leukemia, 259 received chemotherapy, 55 transplantation from compatible related and 43 from unrelated donors. The 5-year disease-free survival was 44.2% overall and 42.5% for chemotherapy only patients. The chemotherapy conditional 5-year disease-free survival increased to 44.4%, 47.6%, 51.7%, and 60.4% in patients who maintained their first remission for at least 3, 6, 9, and 12 months respectively. The overall outcome was superior to that obtained with chemotherapy-only at any time-point. The relative advantage of transplant from compatible related donors in very-high-risk childhood acute lymphoblastic leukemia was consistent for any time elapsed in first remission. |
| Balgobind BV, Hollink IH, Reinhardt D, van Wering ER, de Graaf SS, Baruchel A, Stary J, Beverloo HB, de Greef GE, Pieters R, Zwaan CM, van den Heuvel-Eibrink MM |
Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique. [+] |
European journal of cancer 2010, |
|
| Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukaemia (AML), and are associated with poor prognosis. In adult AML, MLL-PTD is only detected in patients with trisomy 11 or internal tandem duplications of FLT3 (FLT3-ITD). To date, studies in paediatric AML are scarce, and reported large differences in the frequency of MLL-PTD, frequently utilising mRNA RT-PCR only to detect MLL-PTDs. We studied the frequency of MLL-PTD in a large cohort of paediatric AML (n=276) and the results from two different methods, i.e. mRNA RT-PCR, and multiplex ligation-dependent probe amplification (MLPA), a method designed to detect copy number differences of specific DNA sequences. In some patients with an MLL-rearrangement, MLL-PTD transcripts were detected, but were not confirmed by DNA-MLPA, indicating that DNA-MLPA can more accurately detect MLL-PTD compared to mRNA RT-PCR. In paediatric AML, MLL-PTD was detected in 7/276 patients (2.5%). One case had a trisomy 11, while the others had normal cytogenetics. Furthermore 4 of the 7 patients revealed a FLT3-ITD, which was significantly higher compared with the other AML cases (p=0.016). In conclusion, using DNA-MLPA as a novel screenings technique in combination with mRNA RT-PCR a low frequency of MLL-PTD in paediatric AML was found. Larger prospective studies are needed to further define the prognostic relevance of MLL-PTD in paediatric AML. |
| Balduzzi A, Galimberti S, Valsecchi MG, Bonanomi S, Conter V, Barth A, Rovelli A, Henze G, Biondi A, von Stackelberg A |
Autologous purified peripheral blood stem cell transplantation compare to chemotherapy in childhood acute lymphoblastic leukemia after low-risk relapse. [+] |
Pediatric blood & cancer 2011, 57: 654 |
|
| The treatment of childhood B-cell precursor acute lymphoblastic leukemia (ALL) after isolated extramedullary or late relapse is mostly based on chemotherapy or allogeneic transplantation. The aim of this study is to provocatively assess the role of purified autologous transplantation compared with best chemotherapy results in the same setting. |
| Balcerek M, Reinmuth S, Hohmann C, Keil T, Borgmann-Staudt A |
Suspected infertility after treatment for leukemia an solid tumors in childhood and adolescence. [+] |
Dtsch Arztebl Int 2012, 109 |
|
| Background: With improved cure rates of cancer in children and adolescents, the long-term effects of oncological treatment, including impaired fertility, have become an important clinical issue.
Methods: In 2008, we conducted a nationwide survey in Germany in which we asked 4689 female and male patients who had been treated for cancer in childhood or adolescence for information on menstruation, previous fertility testing (if any), attempts to conceive, and pregnancies. In a complementary study carried out in 2009, 748 former cancer patients in Berlin were offered hormone testing and sperm analysis. The defined criteria for suspected infertility were, in women, anti-muellerian hormone levels below 0.1 ng/mL; in men, FSH levels above 10 IU/L and inhibin B levels below 80 pg/mL, or azoospermia.
Results: The respondents to the nationwide survey included 1476 leukemia survivors and 1278 persons who had had a solid tumor. 104 former leukemia patients and 96 former solid tumor patients had already undergone fertility testing, leading to the suspicion of infertility in 26% and 34% of the persons in these respective groups (95% confidence intervals [CI], 18%–34% and 25%–43%). The patients who were tested in the Berlin study included 59 leukemia survivors and 104 persons who had had a solid tumor. The frequency of suspected infertility in these two groups was 25% and 27%, respectively (95% CI, 14%–36% and 18%–36%).
Conclusion: Up to one-third of adults who undergo fertility testing after having been treated for cancer in childhood or adolescence have suspected infertility. Patients and their parents should be counseled about the possibility of infertility and about fertility-preserving measures. |
| Bamberg M, Kortmann RD, Calaminus G, Becker G, Meisner C, Harms D, Göbel U |
Radiation therapy for intracranial germinoma: results of the German cooperative prospective trials MAKEI 83/86/89. [+] |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1999, 17: 2585 |
|
| PURPOSE: A multicenter prospective trial was conducted (Maligue Keimzelltümoren [MAKEI] 83/86/89) to assess outcome in intracranial germinoma after treatment with radiotherapy alone at reduced doses. PATIENTS AND METHODS: Between 1983 and 1993, 60 patients with histologically (n = 58) or cytologically (n = 2) confirmed germinoma were enrolled onto the study. Patients received radiotherapy alone (craniospinal axis/local boost). In the MAKEI 83/86 study (involving 11 patients), the dose to the craniospinal axis was 36 Gy and the dose to the tumor region was 14 Gy. In the MAKEI 89 study (involving 49 patients), doses were 30 and 15 Gy, respectively. RESULTS: Median patient age was 13 years (range, 6 to 31 years). Complete remission was achieved in all patients. The estimated (Kaplan-Meier) 5-year relapse-free survival rate was 91.0% +/- 3.9% at a mean follow-up of 59.5 months (range, 3 to 180 months); the estimated overall survival rate was 93.7% +/- 3.6%. Relapse occurred in five patients 10 to 33 months (mean, 18.4 months) after diagnosis (one patient developed a spinal canal metastasis and underwent salvage radiotherapy and chemotherapy; four patients had metastases outside the CNS and underwent salvage chemotherapy alone). Four patients died: one died from disease, two died from therapy-related complications, and one committed suicide. Acute complications with long-lasting sequelae were tumor or surgery related (three cases of blindness, six of reduced vision, two of hemiparesis). Psychosocial development was normal in the majority of patients. CONCLUSION: Radiotherapy directed toward the craniospinal axis or tumor site alone at decreased dose levels is effective. To reduce the risk of late side effects, further attempts to decrease total doses are justified. In cases of recurrent disease, chemotherapy administered outside the CNS is the treatment of choice. |
| Banning U, Barthel H, Mauz-Körholz C, Kluge R, Körholz D, Sabri O |
Effect of drug-induced cytotoxicity on glucose uptake in Hodgkin's lymphoma cells. [+] |
European journal of haematology 2006, 77: 102 |
|
| BACKGROUND: In Hodgkin's lymphoma, F-18-fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) is used for staging and response evaluation after chemotherapy. However, drug-mediated downregulation of glucose uptake in viable Hodgkin's lymphoma cells might limit the use of FDG-PET. METHODS: We analyzed the effect of etoposide on cell viability and uptake of F-18-fluoro-deoxy-D-glucose or the glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) in vitro. RESULTS: Etoposide induced a dose-dependent cytotoxicity in HDLM-2 cells which was significantly correlated with reduced FDG uptake. However, it also significantly increased the portion of viable cells which did not take up 2-NBDG. Interestingly, etoposide-induced cytotoxicity was mainly mediated via caspase-dependent mechanisms, whereas the cell death induced by deprivation of glucose was mediated via caspase-independent mechanisms. CONCLUSION: Etoposide-mediated reduction of glucose uptake by Hodgkin's lymphoma cells is mainly caused by cell death. In a small fraction of viable cells, etoposide might downregulate glucose transporters and/or hexokinase activity and by that inhibit glucose uptake. This, however, might not lead to false-negative results of response evaluation in Hodgkin's lymphoma patients after chemotherapy, because inhibition of glucose uptake itself seems to be a strong inducer of cell death. Altogether, this study provides important in vitro evidence to clarify the mechanisms by which FDG-PET monitors the effect of anti-cancer treatment in Hodgkin's lymphoma patients. |
| Bandapalli OR, Zimmermann M, Kox C, Stanulla M, Schrappe M, Ludwig WD, Koehler R, Muckenthaler MU, Kulozik AE |
NOTCH1 activation clinically antagonizes the unfavorable effect of PTEN inactivation in BFM-treated children with precursor T-cell acute lymphoblastic leukemia. [+] |
Haematologica 2013, Epub ahead of print |
|
| Abstract Background: Despite improvements of treatment results for pediatric T-cell acute lymphoblastic leukemia (T-ALL), approximately 20% of patients relapse with dismal prognosis. Phosphatase and tensin homolog (PTEN) inactivation and NOTCH1 activation are known frequent leukemogenic events but their effect on outcome have been controversial. Design and methods: We analysed the effect of PTEN inactivation and its interaction with NOTCH1 activation on treatment response and long term outcome in 301 ALL-BFM treated children with T-cell acute lymphoblastic leukemia. Results: We identified PTEN mutations in 52/301 (17.3%) of patients, which in univariate analyses was significantly associated with increased resistance to induction chemotherapy and a trend towards poor long-term outcome. By contrast, patients with inactivating PTEN and activating NOTCH1 mutations showed marked sensitivity to induction treatment and excellent long term outcome, which was similar to patients with NOTCH1 mutations only and more favorable than in patients with PTEN mutations only. Notably, in the subgroup of patients with a prednisone- and MRD-response based medium risk profile PTEN-mutations without co-existing NOTCH1-mutations represented an MRD-independent highly significant high risk biomarker. Conclusions: Mutations of PTEN highly significantly indicate a poor prognosis in patients who have been stratified to the medium risk group of the BFM-protocol. This effect is clinically neutralized by NOTCH1 mutations. Although these results are not yet explained by an obvious molecular mechanism, they contribute to the development of new molecularly defined stratification algorithms. Furthermore, these data have unexpected potential implications for the development of NOTCH1 inhibitors in the treatment of T-cell acute lymphoblastic leukemia in general and in those with a combination of PTEN and NOTCH1 mutations in particular. |
| Bartram C, Ludwig W, Hiddemann W, Lyons J, Buschle M, Ritter J, Harbott J, Fröhlich A, Janssen J |
Acute myeloid leukemia: analysis of ras gene mutations and clonality defined by polymorphic X-linked loci. |
Leukemia 1989, 3: 247 |
|
| Bartram CR, Schrauder A, Köhler R, Schrappe M |
Akute lymphoblastische Leukämie bei Kindern (Übersichtsarbeit). |
Dtsch Arztebl Int 2012; 109: 652 |
|
| Bastian L, Einsiedel HG, Henze G, Seeger K, Shalapour S |
The sequence of application of methotrexate and histone deacetylase inhibitors determines either a synergistic or an antagonistic response in childhood acute lymphoblastic leukemia cells. |
Leukemia 2010 Nov 12; |
|
| Bastian L, Hof J, Pfau M, Fichtner I, Eckert C, Henze G, Prada J, von Stackelberg A, Seeger K, Shalapour S |
Synergistic activity of bortezomib and HDACi in preclinical models of B-cell precursor acute lymphoblastic leukemia via modulation of p53, PI3K/AKT, and NF-κB. [+] |
Clinical cancer research 2013, 19: 1445 |
|
| Relapse of disease and subsequent resistance to established therapies remains a major challenge in the treatment of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). New therapeutic options, such as proteasome and histone deacetylase inhibitors (HDACi) with a toxicity profile differing from that of conventional cytotoxic agents, are needed for these extensively pretreated patients. |
| Baumgarten E, Schmid H, Pohl U, Brzoska J, Linderkamp C, Siegert W, Henze G |
Low-dose natural interleukin-2 and recombinant interferon-gamma following autologous bone marrow grafts in pediatric patients with high-risk acute leukemia. |
Leukemia 1994, 8: 850 |
|
| Bauer A, Savelyeva L, Claas A, Praml C, Berthold F, Schwab M |
Smallest region of overlapping deletion in 1p36 in human neuroblastoma. |
Genes Chromosomes Cancer 2001, 31: 228 |
|
| Bauer J, Jürgens H, Frühwald MC |
Important aspects of nutrition in children with cancer. [+] |
Advances in nutrition (Bethesda, Md.) 2011, 2: 67 |
|
| Adequate nutrition during cancer plays a decisive role in several clinical outcome measures, such as treatment response, quality of life, and cost of care. However, the importance of nutrition in children and young adults with malignancies is still an underestimated topic within pediatric oncology. The importance of our work is to reinforce and indicate that malnutrition in children with cancer should not be accepted at any stage of the disease or tolerated as an inevitable process. Unique to our manuscript is the close collaboration, the exchange of knowledge and expertise between pediatric oncologists and a nutritional specialist, as well as the comprehension of the mechanisms during cancer cachexia and malnutrition. We provide a critical review of the current state of research and new knowledge related to nutritional management in childhood cancer. |
| Beck D, Creutzig U, Riehm H |
Myelodysplastic and myeloproliferative syndromes in children. |
Monogr in Paediat 1986, 153 |
|
| Becker K, Berthold F |
Plasma neurotensin: lack of a differentiation and tumor marker in children with neuroblastoma. |
Pediatr Hematol Oncol 1992, 9: 269 |
|
| Beck J, Winkler K, Niethammer D, Brandis M, Hertzberg H, Hardt von, Greil J, Überall M, Rossi R, Lamprecht-Dinnesen A |
After-care of children and young adults surviving cancer. Initial recommendations by the late sequelae study group. |
Klin Pädiatr 1995, 207: 186 |
|
| Beck J, Hertzberg H, Kochendörfer S, Meier W, Göbel U, Greil J, Langer T |
Neuropsychologische Spätfolgen nach Behandlung einer akuten lymphoblastischen Leukämie im Kindesalter. |
Klin Onkol 1997, 11 |
|
| Beck J, Dopfer R, Gadner H, Hertzberg H, Langer T, Niethammer D, Zoubek A |
Besondere Aspekte in der Onkologie. Spätfolgen nach antineoplastischer Therapie. |
Jugendmedizin 1999, 792 |
|
| Beck J, Dörr H, Langer T, Bielack S, Rossi R, Gutjahr P |
Spätfolgen der antineoplastischen Behandlung im Kindesalter. Die Nachsorge der von einer Krebserkrankung geheilten Kinder und Jugendlichen, in Schmoll H-J, Höffken K, Possinger K (Hrsg.): |
Kompendium Internistische Onkologie, Berlin, Springer 1999, 1462 |
|
| Beck J |
Secondary neoplasms in 5-year survivors of cancer in childhood. |
Strahlenther Onkol 2002, 178: 167 |
|
| Beekman R, Valkhof MG, Sanders MA, van Strien PM, Haanstra JR, Broeders L, Geertsma-Kleinekoort WM, Veerman AJ, Valk PJ, Verhaak RG, Löwenberg B, Touw IP |
Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia. [+] |
Blood 2012, 119: 5071 |
|
| Severe congenital neutropenia (SCN) is a BM failure syndrome with a high risk of progression to acute myeloid leukemia (AML). The underlying genetic changes involved in SCN evolution to AML are largely unknown. We obtained serial hematopoietic samples from an SCN patient who developed AML 17 years after the initiation of G-CSF treatment. Next- generation sequencing was performed to identify mutations during disease progression. In the AML phase, we found 12 acquired nonsynonymous mutations. Three of these, in CSF3R, LLGL2, and ZC3H18, co-occurred in a subpopulation of progenitor cells already in the early SCN phase. This population expanded over time, whereas clones harboring only CSF3R mutations disappeared from the BM. The other 9 mutations were only apparent in the AML cells and affected known AML-associated genes (RUNX1 and ASXL1) and chromatin remodelers (SUZ12 and EP300). In addition, a novel CSF3R mutation that conferred autonomous proliferation to myeloid progenitors was found. We conclude that progression from SCN to AML is a multistep process, with distinct mutations arising early during the SCN phase and others later in AML development. The sequential gain of 2 CSF3R mutations implicates abnormal G-CSF signaling as a driver of leukemic transformation in this case of SCN. |
| Beger C, Gerdes K, Lauten M, Tissing W, Fernandez-Munoz I, Schrappe M, Welte K |
Expression and structural analysis of glucocorticoid receptor isoform gamma in human leukaemia cells using an isoform-specific real-time polymerase chain reaction approach. |
Br J Haematol 2003, 122: 245 |
|
| Behrends U, Jandl T, Golbeck A, Lechner B, Muller-Weihrich S, Schmid I, Till H, Berthold F, Voltz R, Mautner J |
Novel products of the HUD, HUC, NNP-1 and alpha-internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library. |
Int J Cancer 2002, 100: 669 |
|
| Behnisch W, Muckenthaler M, Kuloz ik, A |
Eisenmangelanämie. |
AWMF-Leitlinien 2010 |
|
| BEIR Committee |
Health Risks From Exposure to Low Levels of Ionizing Radiation. |
BEIR VII Phase 2 2006 |
|
| Beltinger C, Bohler T, Karawajew L, Ludwig W, Schrappe M, Debatin K |
Mutation analysis of CD95 (APO-1/Fas) in childhood B-lineage acute lymphoblastic leukaemia. |
Br J Haematol 1998, 102: 722 |
|
| Beltinger C, Kurz E, Bohler T, Schrappe M, Ludwig W, Debatin K |
CD95 (APO-1/Fas) mutations in childhood T-lineage acute lymphoblastic leukemia. |
Blood 1998, 91: 3943 |
|
| Bellaton E, Bertozzi AI, Behar C, Chastagner P, Brisse H, Sainte-Rose C, Doz F, Desjardins L |
Neoadjuvant chemotherapy for extensive unilateral retinoblastoma. [+] |
The British journal of ophthalmology 2003, 87: 327 |
|
| The role of neoadjuvant chemotherapy was studied when first line enucleation cannot be safely performed in unilateral extensive retinoblastoma (major buphthalmia or radiologically detectable optic nerve involvement). |
| Belson M, Kingsley B, Holmes A |
Risk factors for acute leukemia in children: a review. [+] |
Environmental health perspectives 2007, 115: 138 |
|
| Although overall incidence is rare, leukemia is the most common type of childhood cancer. It accounts for 30% of all cancers diagnosed in children younger than 15 years. Within this population, acute lymphocytic leukemia (ALL) occurs approximately five times more frequently than acute myelogenous leukemia (AML) and accounts for approximately 78% of all childhood leukemia diagnoses. Epidemiologic studies of acute leukemias in children have examined possible risk factors, including genetic, infectious, and environmental, in an attempt to determine etiology. Only one environmental risk factor (ionizing radiation) has been significantly linked to ALL or AML. Most environmental risk factors have been found to be weakly and inconsistently associated with either form of acute childhood leukemia. Our review focuses on the demographics of childhood leukemia and the risk factors that have been associated with the development of childhood ALL or AML. The environmental risk factors discussed include ionizing radiation, non-ionizing radiation, hydrocarbons, pesticides, alcohol use, cigarette smoking, and illicit drug use. Knowledge of these particular risk factors can be used to support measures to reduce potentially harmful exposures and decrease the risk of disease. We also review genetic and infectious risk factors and other variables, including maternal reproductive history and birth characteristics. |
| Bennett MH, MacLennan KA, Easterling MJ, Vaughan Hudson B, Vaughan Hudson G, Jelliffe AM |
Analysis of histological subtypes in Hodgkin’s disease in relation to prognosis and survival, in Quaglino D, Hayhoe FGJ (eds.): The cytobiology of leukaemias and lymphomas. |
Serono symposia publications from Raven press, New York 1985 |
|
| Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C |
Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7). A report of the French-American-British Cooperative Group. |
Annals Internal Medicine 1985, 103: 460 |
|
| Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C |
Proposed revised criteria for the classification of acute myeloid leukemia. |
Annals Internal Medicine 1985, 103: 626 |
|
| Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C |
Proposal for the recognition of minimally differentiated acute myeloid leukaemia (AML-M0). |
Br J Haematol 1991, 78: 325 |
|
| Benk V, Rodary C, Donaldson S, Flamant F, Maurer H, Treuner J, Carli M, Gehan E |
Parameningeal rhabdomyosarcoma. |
Int J Radiat Oncol Biol Phys 1996, 36: 533 |
|
| Bénard J, Raguénez G, Kauffmann A, Valent A, Ripoche H, Joulin V, Job B, Danglot G, Cantais S, Robert T, Terrier-Lacombe MJ, Chassevent A, Koscielny S, Fischer M, Berthold F, Lipinski M, Tursz T, Dessen P, Lazar V, Valteau-Couanet D |
MYCN-non-amplified metastatic neuroblastoma with good prognosis and spontaneous regression: a molecular portrait of stage 4S. [+] |
Molecular oncology 2008, 2: 261 |
|
| Stage 4 neuroblastoma (NB) are heterogeneous regarding their clinical presentations and behavior. Indeed infants (stage 4S and non-stage 4S of age <365days at diagnosis) show regression contrasting with progression in children (>365days). Our study aimed at: (i) identifying age-based genomic and gene expression profiles of stage 4 NB supporting this clinical stratification; and (ii) finding a stage 4S NB signature. Differential genome and transcriptome analyses of a learning set of MYCN-non amplified stage 4 NB tumors at diagnosis (n=29 tumors including 12 stage 4S) were performed using 1Mb BAC microarrays and Agilent 22K probes oligo-microarrays. mRNA chips data following filtering yielded informative genes before supervised hierarchical clustering to identify relationship among tumor samples. After confirmation by quantitative RT-PCR, a stage 4S NB's gene cluster was obtained and submitted to a validation set (n=22 tumors). Genomic abnormalities of infant's tumors (whole chromosomes gains or loss) differ radically from that of children (intra-chromosomal rearrangements) but could not discriminate infants with 4S from those without this presentation. In contrast, differential gene expression by looking at both individual genes and whole biological pathways leads to a molecular stage 4S NB portrait which provides new biological clues about this fascinating entity. |
| Benz-Bohm G, Hero B, Gossmann A, Simon T, Körber F, Berthold F |
Focal nodular hyperplasia of the liver in longterm survivors of neuroblastoma How much diagnostic imaging is necessary? [+] |
European journal of radiology 2009, |
|
| OBJECTIVES: Focal nodular hyperplasia of the liver is a tumor-like lesion, uncommon in children, but it has recently been more frequently observed in children treated for malignant diseases, especially neuroblastoma. The aetiology is unclear, the pathogenesis remains controversial. Focal nodular hyperplasia of the liver is suspected to be a sequela of tumor therapy. METHODS: Besides the clinical data we evaluated the imaging modalities needed to diagnose focal nodular hyperplasia of the liver in children with neuroblastoma who have been followed in our institution for more than 5 years. RESULTS: Out of 60 children six developed focal nodular hyperplasia at a median time of 10.5 years after diagnosis of neuroblastoma and 9.4 years after the end of treatment. The diagnosis of focal nodular hyperplasia was based on imaging criteria which are variable in ultrasonography and specific in MRI. Only one child underwent surgical biopsies to rule out liver metastases. CONCLUSIONS: Longterm survivors of neuroblastoma are at risk of developing focal nodular hyperplasia, especially if they underwent toxic chemotherapy and/or radiotherapy to the liver during initial treatment. The recommended diagnostic imaging tools are ultrasonography for detecting liver lesions and MRI for confirming and characterizing these lesions as focal nodular hyperplasia. |
| Benesch M, Siegler N, Hoff K, Lassay L, Kropshofer G, Müller H, Sommer C, Rutkowski S, Fleischhack G, Urban C |
Safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with recurrent or refractory brain tumors: a multi-institutional retrospective study. [+] |
Anti-cancer drugs 2009, 20: 794 |
|
| This retrospective study aimed to evaluate the safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with refractory or recurrent brain tumors. Nineteen heavily pretreated patients (males, n = 14; females, n = 5; median age at diagnosis 8.5 years; range, 1.4-22 years) were given intrathecal liposomal cytarabine on a compassionate use basis for recurrent refractory medulloblastoma (n = 12), mixed germ cell tumor (n = 2), central nervous system primitive neuroectodermal tumors of the pons (n = 1), anaplastic ependymoma (n = 1), anaplastic oligodendroglioma (n = 1), atypical teratoid rhabdoid tumor (n = 1), or rhabdoid papillary meningioma (n = 1). Eighteen patients received concomitant systemic radiochemotherapy. A total of 88 intrathecal injections of liposomal cytarabine (dose range, 20-50 mg) were administered with concomitant dexamethasone prophylaxis. The median number of doses per patient was four (range, 1-10). Duration of treatment ranged from (1/2) to 10 months. Eleven patients (57.9%) did not show any side effects, whereas eight patients (42.1%) developed side effects related to either chemical arachnoiditis (n = 4) or neurological progression (n = 2). Less typical treatment-related symptoms (e.g. lethargy, ataxia, and slurred speech) were observed in two patients. Treatment with intrathecal liposomal cytarabine was discontinued twice because of side effects. In conclusion, although intrathecal liposomal cytarabine was generally well tolerated, it should be used cautiously and only with dexamethasone prophylaxis in extensively pretreated patients with recurrent brain tumors. Proof of efficacy requires a prospective single-agent phase II study. |
| Benesch M, Sperl D, von Bueren AO, Schmid I, von Hoff K, Warmuth-Metz M, Ferrari R, Lassay L, Kortmann RD, Pietsch T, Rutkowski S |
Primary central nervous system primitive neuroectodermal tumors (CNS-PNETs) of the spinal cord in children: four cases from the German HIT database with a critical review of the literature. [+] |
J Neurooncol 2010, Epub ahead of print |
|
| Approximately 30-50% of patients with intracranial primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) develop spinal metastases. In contrast, primary spinal CNS-PNETs are extremely uncommon. The database and study records of the German/Austrian brain tumor trials HIT 91, HIT SKK 92, and HIT 2000 were retrospectively reviewed to describe clinical features, treatment modalities, and outcome of children with primary CNS-PNETs of the spinal cord who were registered as observational patients. Out of 1,248 patients with medulloblastomas or CNS-PNETs registered in the HIT database four patients (female, n = 3) with primary CNS-PNETs of the spinal cord were identified. Age at diagnosis was 10, 16, 23, and 174 months. Location of primary tumors was medulla oblongata-T3, C2-T1, T10-L2, T7-T10. Two patients had metastatic disease at diagnosis. Complete and incomplete resection was performed in one patient each, whereas two patients underwent a biopsy only. Two patients received chemotherapy only, in accordance with the HIT 91 trial (sandwich chemotherapy arm). They developed disease progression and died six months after diagnosis. One patient was given chemotherapy in accordance with the HIT 2000 trial followed by craniospinal radiotherapy and four courses of maintenance chemotherapy. The patient is in complete remission almost four years after diagnosis. The fourth patient developed disease progression while receiving induction chemotherapy. Hence, chemotherapy was switched to a modified Head Start protocol. After three cycles he underwent double autologous stem cell transplantation and craniospinal irradiation. Forty months after diagnosis the patient is alive and well, but surveillance MRIs still show nodular enhancing lesions in the area of the primary tumor and intracranial meningeal enhancement. Primary CNS-PNETs of the spinal cord probably require multimodal treatment including radiotherapy to achieve sustained tumor control. |
| Benesch M, Weber-Mzell D, Gerber NU, von Hoff K, Deinlein F, Krauss J, Warmuth-Metz M, Kortmann RD, Pietsch T, Driever PH, Quehenberger F, Urban C, Rutkowski S |
Ependymoma of the spinal cord in children and adolescents: a retrospective series from the HIT database. [+] |
J Neurosurg Pediatr 2010, 6: 137 |
|
| OBJECT: Reports on spinal cord ependymoma in children are rare. The aim of this study was to evaluate the clinical spectrum, treatment, and outcome of children with primary ependymoma of the spinal cord who were registered in the database of the pediatric German brain tumor studies Hirntumor (HIT) '91 and HIT 2000.
METHODS: Between 1991 and 2007, 29 patients (12 male and 17 female, median age at diagnosis 13.6 years) with primary spinal cord ependymoma (myxopapillary ependymoma WHO Grade I, II, and III tumors in 6, 17, and 6 patients, respectively) were identified. Four patients had neurofibromatosis Type 2.
RESULTS: With a median follow-up of 4.2 years (range 0.48-15 years), 28 patients (96.6%) were alive. Seven patients (24.1%) developed progressive disease or relapse, 2 after gross-total resection (GTR) and 5 after incomplete resection or biopsy. One patient with anaplastic ependymoma (WHO Grade III) died 65 months after diagnosis of disease progression. Primary adjuvant treatment (radiotherapy, chemotherapy, or both) was used in 8 (50%) of 16 patients following GTR and in 9 (82%) of 11 patients who underwent less than a GTR. Three additional patients were treated adjuvantly following progression. Estimated progression-free survival and overall survival rates at 5 years were 72.3% (95% CI 50%-86%) and 100%, respectively. Progression-free survival at 5 years is 84.4% (95% CI 50%-96%) for patients following GTR compared with 57.1% (95% CI 25%-69%) for patients who achieved a less than GTR (p = 0.088, log-rank test). A high relapse incidence (4 of 6) was observed among patients with myxopapillary ependymoma.
CONCLUSIONS: Gross-total resection is the mainstay of treatment for patients with primary spinal cord ependymoma and may be achieved in about 50% of the patients using modern surgical techniques. Primary adjuvant treatment was commonly used in children with spinal cord ependymoma irrespective of the extent of resection or tumor grade. The impact of adjuvant treatment on progression-free and overall survival has to be investigated in a prospective trial. |
| Benesch M, Leuschner I, Wardelmann E, Thielen M, Schmid I, Kontny U, Ebetsberger G, Frey E, Graf N, Schneider DT, Kremens B, Amann G, Urban C, Schlemmer M, Quehenberger F, Klingebiel T, Dantonello T, Koscielniak E |
Gastrointestinal stromal tumours in children and young adults: A clinicopathologic series with long-term follow-up from the database of the Cooperative Weichteilsarkom Studiengruppe (CWS). [+] |
Eur J Cancer 2011, 47: 1692-8. Epub 2011 Apr 11. |
|
| Studies on gastrointestinal stromal tumours (GIST) in the paediatric population are limited to case reports or small case series.
PATIENTS AND METHODS:
We conducted a retrospective study to describe the long-term outcome of children and adolescents with GIST registered in the database of the Cooperative Weichteilsarkom Studiengruppe (CWS).
RESULTS:
Sixteen patients (female, n=11) were identified. Median age at diagnosis was 13.5years. In four female patients presence of thoracic masses in addition to GIST led to the diagnosis of complete or incomplete Carney triad. Three female patients had metastatic disease at diagnosis, the remaining thirteen GIST were localised. The stomach was the most common primary site of the tumour, followed by the small bowel and colon/abdomen. All patients underwent tumour resection. Receptor tyrosine kinase inhibitors (RTKI) were administered in five patients. With a median follow-up of 96months all patients are alive, nine of them in first CR. Four female patients developed local or distant recurrence; three of them achieved second CR and one a PR. Two individuals have extensive progressive (n=1) or stable (n=1) disease. Estimated progression-free survival at 5years is 0.63 (95%CI: 0.50-0.86).
CONCLUSIONS:
Although long-term overall survival is favourable, approximately 30 percent of patients develop disease progression. International cooperation in registration, tissue collection and molecular studies are required to obtain reliable data on the clinical course of these rare tumours in the paediatric population. Biological studies are a prerequisite for initiation of studies with RTKI. |
| Berry MP, Jenkin RD, Keen CW, Nair BD, Simpson WJ |
Radiation treatment for medulloblastoma. A 21-year review. [+] |
J Neurosurg 1981, 43 |
|
| One hundred and twenty-two patients with medulloblastoma received postoperative irradiation at the Princess Margaret Hospital, Toronto, from 1958 to 1978, inclusive. The surgical procedure in these patients was total resection (44 patients), subtotal resection (66 patients), or biopsy alone (12 patients). Twenty-five patients received adjuvant chemotherapy. Overall 5- and 10-year survival rates were 56% and 43%, respectively. Improved survival rates were associated with an increased degree of resection and with posterior fossa radiation doses of 5200 rads or more. The posterior fossa was the common site of first relapse (in 56 patients, 46%). Systemic metastases at first relapse occurred in 18 of 52 patients (35%), and were associated with the use of ventriculosystemic shunts. Millipore filters did not prevent systemic relapse in shunted patients. A subset of 15 patients who received a posterior fossa dose of 5200 rads or more after a total resection had a 5-year survival rate of 77%, which remained constant to 10 years. This result is considered to be the upper limit that can be achieved by current treatment methods. |
| Berthold F, Creutzig U, Lampert F |
Effective remission induction in children with recurrent acute myeloid leukemia by mAMSA, Ara-C, and VP 16. |
Haematology and Blood Transfusion 1987, 30: 406 |
|
| Berthold F |
Neuroblastom-Screening. |
Münchn Med Wschr 1991, 22 |
|
| Berthold F, Engelhardt-Fahrner U, Schneider A, Schumacher R, Zieschang J |
Age dependence and prognostic impact of neuron specific enolase (NSE) in children with neuroblastoma. |
In Vivo 1991, 5: 245 |
|
| Berthold F, Himmelmann U, Pohl U |
Natural interleukin-2 and lymphokine activated killer cells in the treatment of neuroblastoma in vitro and in vivo. |
Prog Clin Biol Res 1991, 366: 417 |
|
| Berthold F, Hunneman D, Kaser H, Harms D, Bertram U, Erttmann R, Schilling F, Treuner J, Zieschang J |
Neuroblastoma screening: arguments from retrospective analysis of three German neuroblastoma trials. |
American Journal Pediatric Hematology Oncology 1991, 13: 8 |
|
| Berthold F, Hunneman D, Harms D, Kaser H, Zieschang J |
Serum vanillylmandelic acid/homovanillic acid contributes to prognosis estimation in patients with localised but not with metastatic neuroblastoma. |
Eur J Cancer 1992, 28A: 1950 |
|
| Berthold F, Sander J, Baillot A, Hunneman D, Michaelis J |
The "Lower Saxony/Northern Rhine-Westphalia" Neuroblastoma Screening Project. |
Klin Pädiatr 1992, 204: 288 |
|
| Berthold F, Trechow R, Utsch S, Zieschang J |
Prognostic factors in metastatic neuroblastoma. A multivariate analysis of 182 cases. |
Am J Pediatr Hematol Oncol 1992, 14: 207 |
|
| Bergsagel DJ, Finegold MJ, Butel JS, Kupsky WJ, Garcea RL |
DNA sequences similar to those of simian virus 40 in ependymomas and choroid plexus tumors of childhood. |
N Engl J Med 1992, 326: 988 |
|
| Berthold F |
Neuroblastom. Modelltumor und Herausforderung für den Kinderarzt. |
Monatschr Kinderheilkd 1994, 142: 296 |
|
| Berthold F, Kassenbohmer R, Zieschang J |
Multivariate evaluation of prognostic factors in localized neuroblastoma. |
Am J Pediatr Hematol Oncol 1994, 16: 107 |
|
| Berthold F, Hero B, Breu H, Christiansen H, Erttmann R, Gnekow A, Herrmann F, Klingebiel T, Lampert F, Muller-Weihrich S, Weinel P |
The recurrence patterns of stages I, II and III neuroblastoma. |
Ann Oncol 1996, 7: 183 |
|
| Berthold F |
Commentary on. |
Eur J Cancer 1997, 33: 1437 |
|
| Berthold F, Sahin K, Hero B, Christiansen H, Gehring M, Harms D, Horz S, Lampert F, Schwab M, Terpe J |
The current contribution of molecular factors to risk estimation in neuroblastoma patients. |
Eur J Cancer 1997, 33: 2092 |
|
| Berthold F, Hero B |
Neuroblastom in Huber/Hiddemann/Batram (Hrsg.) |
Klinische Onkologie 1998 |
|
| Berthold F, Hero B, Horz S, Jobke B, Boos J, Bretz R, Burdach S, Claviez A, Henze G, Jorch N, Klingebiel T, Kremens B, Kühl J, Schwabe D |
Sind Spontanregressionen beim Neuroblastom verspätete embryofetale Involutionen? |
Spontanremissionen bei Krebserkrankungen 1998 |
|
| Berthold F |
Maligne Erkrankungen des lymphatischen und histiozytären Systems, in Niessen K (Hrsg.), Maligne Tumoren, Thieme. |
Pädiatrie 1999, 369 |
|
| Berthold F, Baillot A, Hero B, Schurr P, Nerenz A, Hunneman D, Sander J |
Which cases are found and missed by neuroblastoma screening at 1 year? |
J Clin Oncol 1999, 17 |
|
| Berthold F, Hero B |
Neuroblastoma. |
Drugs 2000, 59: 1261 |
|
| Berthold F, Herold R |
Die Pädiatrische Onkologie und Hämatologie auf dem Weg in die neue Krankenhausfinanzierung. |
Klinische Pädiatrie 2002, 214: 145 |
|
| Berthold F, Hero B, Kremens B, Handgretinger R, Henze G, Schilling FH, Schrappe M, Simon T, Spix C |
Long-term results and risk profiles of patients in five consecutive trials (1979-1997) with stage 4 neuroblastoma over 1 year of age. [+] |
Cancer letters 2003, 197(1-2): 11 |
|
| During the last two decades new diagnostic and therapeutic tools have been utilized to improve the poor survival chances of children with stage 4 neuroblastoma. This study reviews the risk profiles and the long-term outcome of patients from five consecutive German neuroblastoma trials. A total of 96% of all German patients registered at the German childhood cancer registry with neuroblastoma stage 4 over 1 year of age at diagnosis entered one of the trials during 1979-2001. Eight hundred and twenty-eight consecutive children were analyzed retrospectively. In spite of having significantly improved diagnostic tools like bone marrow superstaging and mIBG scintigraphy the stage 4 incidence did not increase after reaching completeness of the registry (5.4 cases/100,000 children at 1-14 years of age; P=0.52). The distribution of the primary tumors and of metastases was constant over the periods. The amount of bone marrow infiltration did not change with time. The risk factors lactate dehydrogenase, ferritin and MYCN, and the clinical risk groups 4A, 4B, 4C also remained constant over the trials with a few exceptions for NB97. The 5-year event free survival increased from 0.01+/-0.01 (NB79) to 0.14+/-0.03 (NB85), 0.16+/-0.04 (NB82), 0.27+/-0.02 (NB90), and 0.33+/-0.04 (NB97). The overall survival rates improved similarly from 0.04 (NB79) to 0.44 (NB97). In conclusion, the improved survival was associated with better treatment and not caused by lower risk profiles in stage 4 neuroblastoma patients. |
| Berthold F, Simon T |
Clinical Presentation. |
In: Cheung NK, Cohn SL (Hrsg.). Neuroblastoma Springer Verlag. 2005, 63 |
|
| Berthold F, Boos J, Burdach S, Erttmann R, Henze G, Hermann J, Klingebiel T, Kremens B, Schilling FH, Schrappe M, Simon T, Hero B |
Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. [+] |
The lancet oncology 2005, 6: 649 |
|
| BACKGROUND: Myeloablative megatherapy is commonly used to improve the poor outlook of children with high-risk neuroblastoma, yet its role is poorly defined. We aimed to assess whether megatherapy with autologous stem-cell transplantation could increase event-free survival and overall survival compared with maintenance chemotherapy. METHODS: 295 patients with high-risk neuroblastoma (ie, patients with stage 4 disease aged older than 1 year or those with MYCN-amplified tumours and stage 1, 2, 3, or 4S disease or stage 4 disease and <1 year old) were randomly assigned to myeloablative megatherapy (melphalan, etoposide, and carboplatin) with autologous stem-cell transplantation (n=149) or to oral maintenance chemotherapy with cyclophosphamide (n=146). The primary endpoint was event-free survival. Secondary endpoints were overall survival and the number of treatment-related deaths. Analyses were done by intent to treat, as treated, and treated as randomised. FINDINGS: Intention-to-treat analysis showed that patients allocated megatherapy had increased 3-year event-free survival compared with those allocated maintenance therapy (47% [95% CI 38-55] vs 31% [95% CI 23-39]; hazard ratio 1.404 [95% CI 1.048-1.881], p=0.0221), but did not have significantly increased 3-year overall survival (62% [95% CI 54-70] vs 53% [95% CI 45-62]; 1.329 [0.958-1.843], p=0.0875). Improved 3-year event-free survival and 3-year overall survival were also recorded for patients given megatherapy in the as-treated group (n=212) and in the treated-as-randomised group (n=145). Two patients died from therapy-related complications during induction treatment. No patients given maintenance therapy died from acute treatment-related toxic effects. Five patients given megatherapy died from acute complications related to megatherapy. INTERPRETATION: Myeloablative chemotherapy with autologous stem-cell transplantation improves the outcome for children with high-risk neuroblastoma despite the raised risk of treatment-associated death. |
| Bernstein M, Kovar H, Paulussen M, Randall RL, Schuck A, Teot LA, Jürgens H |
Ewing's sarcoma family of tumors: current management. [+] |
The oncologist 2006, 11: 503 |
|
| Ewing's sarcoma is the second most frequent primary bone cancer, with approximately 225 new cases diagnosed each year in patients less than 20 years of age in North America. It is one of the pediatric small round blue cell tumors, characterized by strong membrane expression of CD99 in a chain-mail pattern and negativity for lymphoid (CD45), rhabdomyosarcoma (myogenin, desmin, actin) and neuroblastoma (neurofilament protein) markers. Pathognomonic translocations involving the ews gene on chromosome 22 and an ets-type gene, most commonly the fli1 gene on chromosome 11, are implicated in the great majority of cases. Clinical presentation is usually dominated by local bone pain and a mass. Imaging reveals a technetium pyrophosphate avid lesion that, on plain radiograph, is destructive, diaphyseal and classically causes layered periosteal calcification. Magnetic resonance best defines the extent of the lesion. Biopsy should be undertaken by an experienced orthopedic oncologist. Approximately three quarters of patients have initially localized disease. About two thirds survive disease-free. Management, preferably at a specialist center with a multi-disciplinary team, includes both local control-either surgery, radiation or a combination-and systemic chemotherapy. Chemotherapy includes cyclic combinations, incorporating vincristine, doxorubicin, cyclophosphamide, etoposide, ifosfamide and occasionally actinomycin D. Topotecan in combination with cyclophosphamide has shown preliminary activity. Patients with initially metastatic disease fare less well, with about one quarter surviving. Studies incorporating intensive therapy followed by stem cell infusion show no clear benefit. New approaches include anti-angiogenic therapy, particularly since vascular endothelial growth factor is an apparent downstream target of the ews-fli1 oncogene. |
| Bernstein M, Kovar H, Paulussen M, Randall, RL, Schuck A, Teot, LA, Juergens, H |
Ewing Sarcoma Family of Tumors: Ewing Sarcoma of Bone and Soft Tissue and the Peripheral Primitive Neuroectodermal Tumors. |
Buch: Principles and Practice of Pediatric Oncology (Ed. Pizzo,P.A.; Poplack,D.G.) 2006, 5th Ed.;Ch.33; 1002 |
|
| Berthold F |
Neuroblastom, in Schmoll H-J, Höffken K, Possinger K (Hrsg) : Kompendium Internistische Onkologie. |
Springer Verlag 2006, XIII, 5567 |
|
| Bernbeck B, Schneider DT, Bernbeck B, Koch S, Teske C, Lentrodt J, Harms D, Göbel U, Calaminus G, MAKEI-Study Group |
Germ cell tumors of the head and neck: report from the MAKEI Study Group. [+] |
Pediatric blood & cancer 2009, 52: 223 |
|
| BACKGROUND: Germ cell tumors (GCTs) of the head and neck region are rare but may pose significant problems for perinatal management as well as surgical and adjuvant therapy. PROCEDURE: Thirty-two prospectively reported patients from the German MAKEI studies (Maligne Keimzelltumoren) were analyzed with regard to perinatal management and long-term survival. RESULTS: Twenty-three tumors were diagnosed around birth and four during the first 3 months of life. All were primarily diagnosed as teratomas, but in two tumors, yolk sac tumor (YST) foci were identified. Another pure teratoma was diagnosed at 12 months. Four tumors were diagnosed after the first year of life and showed YST as leading histology. Most neonates presented with huge tumors causing external airway obstruction. All tumors were resected (complete resection, 16/26 patients with complete surgical information; incomplete resection, 10/26 patients). Eight tumors including five of six YSTs were treated with chemotherapy. In total, six patients relapsed. Relapse rate was higher after incomplete (5/10 patients) than after complete resection (1/16 patients). Accordingly, more relapses were observed in pharyngeal than in neck tumors due to incomplete resection. Nevertheless, half of the patients with incomplete resection remained in remission. One patient with YST died after multiple relapses. CONCLUSIONS: GCTs of the head and neck region require a multidisciplinary approach in specialized centers. Most patients with antenatal tumor growth are identified by ultrasound and delivered preterm by cesarian section. After delivery, immediate intubation and ventilation aim for respiratory stabilization, followed by elective resection. With this approach, outcome was favorable. |
| Berrak SG, Liu DD, Wrede B, Wolff JE |
Which therapy works better in choroid plexus carcinomas? [+] |
J Neurooncol 2010, Epub ahead of print |
|
| Choroid plexus carcinomas (CPCs) are rare tumors with dismal outcome. While it has been established that surgery, radiotherapy, and chemotherapy improve survival, the best chemotherapy drugs for treating this disease still need to be identified. Since CPC is too rare to permit a prospective clinical trial, we performed a meta-analysis to evaluate the effects of individual drugs in patients with CPCs. We expanded a pre-existing database and included all cases of choroid plexus tumors, identified in PubMed through the end of 2007, for a total of 906 patients. At first, we restricted the analysis to patients with histologically confirmed CPC (n = 361) and with residual tumor after surgery (n = 130/361 patients), and we compared response and survival between patients who received a particular drug and those who did not. Response to chemotherapy was documented in 43 patients. Of the drugs used in these patients, etoposide was associated with the highest response rate (17/36). Next survival was compared among all CPC. Kaplan-Meier curves and log-rank tests suggested a statistically significant treatment benefit for cyclophosphamide, etoposide, and carboplatin, while the effect of vincristine was found to be marginally significant (P = 0.07, log rank). Of these, only etoposide's effect could be confirmed in a limited Cox multiple regression analysis. In conclusion, etoposide should be included in future standard treatment protocols. However the survival rates are still unsatisfactory, and additional novel drugs should be studied in prospective multicenter studies. |
| Berrak SG, Liu DD, Wrede B, Wolff JE |
Which therapy works better in choroid plexus carcinomas? [+] |
J Neurooncol 2011, 103: 155 |
|
| Choroid plexus carcinomas (CPCs) are rare tumors with dismal outcome. While it has been established that surgery, radiotherapy, and chemotherapy improve survival, the best chemotherapy drugs for treating this disease still need to be identified. Since CPC is too rare to permit a prospective clinical trial, we performed a meta-analysis to evaluate the effects of individual drugs in patients with CPCs. We expanded a pre-existing database and included all cases of choroid plexus tumors, identified in PubMed through the end of 2007, for a total of 906 patients. At first, we restricted the analysis to patients with histologically confirmed CPC (n = 361) and with residual tumor after surgery (n = 130/361 patients), and we compared response and survival between patients who received a particular drug and those who did not. Response to chemotherapy was documented in 43 patients. Of the drugs used in these patients, etoposide was associated with the highest response rate (17/36). Next survival was compared among all CPC. Kaplan-Meier curves and log-rank tests suggested a statistically significant treatment benefit for cyclophosphamide, etoposide, and carboplatin, while the effect of vincristine was found to be marginally significant (P = 0.07, log rank). Of these, only etoposide's effect could be confirmed in a limited Cox multiple regression analysis. In conclusion, etoposide should be included in future standard treatment protocols. However the survival rates are still unsatisfactory, and additional novel drugs should be studied in prospective multicenter studies. |
| Berentsen S, Tjønnfjord GE |
Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia. [+] |
Blood reviews 2012, [Epub ahead of print] |
|
| Exact diagnosis of the subtype has essential therapeutic consequences in autoimmune hemolytic anemia. Cold-antibody types include primary chronic cold agglutinin disease (CAD) and rare cases of cold agglutinin syndrome (CAS) secondary to cancer or acute infection. Primary CAD is a clonal lymphoproliferative disorder. Not all patients require pharmacological therapy, but treatment seems indicated more often than previously thought. Corticosteroids should not be used to treat primary CAD. Half of the patients respond to rituximab monotherapy; median response duration is 11months. The most efficient treatment to date is fludarabine and rituximab in combination, resulting in responses in 75%, complete responses in 20% and median response duration of more than 66months. Toxicity may be a concern, and an individualized approach is discussed. Erythrocyte transfusions can be given provided specific precautions are undertaken. No evidence-based therapy exists in secondary CAS, but optimal treatment of the underlying disorder is essential when feasible. |
| Berger M, Fernandez-Pineda I, Cabello R, Ramírez-Villar GL, Márquez-Vega C, Nustede R, Linderkamp C, Schmid I, Neth O, Graf N, Agustin JC, Schweinitz DV, Lacher M, Hubertus J |
The Relationship Between the Site of Metastases and Outcome in Children With Stage IV Wilms Tumor: Data From 3 European Pediatric Cancer Institutions. [+] |
Journal of pediatric hematology/oncology 2013, Epub ahead of print |
|
| The aim of this study was to analyze in detail the site of metastasis of stage 4 Wilms tumor (WT) and its correlation with outcome. The databases from 3 major European pediatric cancer institutions were screened for children with WT between 1994 and 2011. Of 208 children identified, 31 (14.9%) had metastases at diagnosis. The lung was affected in 29 children (93.5%) and the liver in 6 children (19.4%). Twenty-seven children (87.1%) had metastases isolated to 1 organ, with the lung being the most common site (80.7%). Five-year overall survival was significantly better in those children with distant disease in either lung or liver (95.8%) compared with those affected in both lung and liver (57.1%, P=0.028). Further, prognostic markers were the response of metastases to preoperative chemotherapy (P=0.0138), high-risk histology (P=0.024), and local stage (P=0.026). Five-year overall survival was 82.1% and 5-year event-free survival was 67.9%. The overall follow-up time was 74.1 and 87.2 (2 to 151) months among survivors, and the treatment-related complication rate was 16.7%. In conclusion, in our series of stage 4 WT, prognosis was excellent if histology was favorable, metastatic disease was isolated to either lungs or liver, and if metastases responded to preoperative chemotherapy. |
| Beutel K, Simon A |
Diagnostics and management of central venous line infections in pediatric cancer patients. |
Klin Pädiatr 2005, 217 Suppl 1:S91 |
|
| Beyermann B, Agthe A, Adams H, Seeger K, Linderkamp C, Goetze G, Ludwig W, Henze G |
Clinical features and outcome of children with first marrow relapse of acute lymphoblastic leukemia expressing BCR-ABL fusion transcripts. BFM Relapse Study Group. |
Blood 1996, 87: 1532 |
|
| Beyermann B, Adams H, Henze G |
Philadelphia chromosome in relapsed childhood acute lymphoblastic leukemia. |
J Clin Oncol 1997, 15: 2231 |
|
| Beyer R, Dörr H |
Observations of reported and measured heights of mothers of short statured children. |
Ann Hum Biol 1998, 25: 387 |
|
| Bundesamt für Strahlenschutz |
Grenzwerte und Dosisbegriffe im Strahlenschutz . |
Webseite des Bundesamtes für Strahlenschutz Stand vom 08.04.2010, aufgerufen 24.06.2011 |
|
| Bundesamt für Strahlenschutz |
Krebs und Leukämie . |
Webseite des Bundesamtes für Strahlenschutz aufgerufen 24.06.2011 |
|
| Bundesamt für Strahlenschutz (BfS) |
Entwarnung mit Einschränkung - Kein erhöhtes Risiko für erwachsene Handynutzer. |
in: WIR - die Zeitschrift der Deutschen Leukämie-Forschungshilfe e.V. und der Deutschen Kinderkrebsstiftung 1/2011 |
|
| Bhatia S, Yasui Y, Robison LL, Birch JM, Bogue MK, Diller L, DeLaat C, Fossati-Bellani F, Morgan E, Oberlin O, Reaman G, Ruymann FB, Tersak J, Meadows AT |
High risk of subsequent neoplasms continues with extended follow-up of childhood Hodgkin's disease: report from the Late Effects Study Group. |
J Clin Oncol 2003, 21: 4386 |
|
| Bidlingmaier C, Olivieri M,Kurnik, K |
Hautblutungen bei Kindern Ist es eine Gerinnungsstörung? [+] |
Monatsschrift Kinderheilkunde 2012, 160, 538 |
|
| Hämatome im Kindesalter sind häufig. Meist sind sie Folge kleinerer Verletzungen und harmlos. Andererseits können sie erste Hinweise auf eine angeborene Gerinnungsstörung sein. Es ist daher wichtig, zu entscheiden, ob es sich um normale blaue Flecken oder aber eine relevante Blutungsneigung handelt. Neben der körperlichen Untersuchung spielen hierbei die Anamnese des Kindes und der Familie eine wichtige Rolle. Bei Verdacht auf eine Gerinnungsstörung muss sich eine ausgedehnte Labordiagnostik anschließen, da die Globalwerte der Gerinnung [aktivierte partielle Thromboplastinzeit (aPTT) und Quick-Wert] nicht hinreichend geeignet sind, häufige Gerinnungsstörungen wie ein Von-Willebrand-Syndrom auszuschließen. Im vorliegenden Beitrag wird das diagnostische Vorgehen mit Schwerpunkt auf relativ häufigen Gerinnungsstörungen beschrieben. |
| Bielack S, Bieling P, Erttmann R, Winkler K |
Intraarterial chemotherapy for osteosarcoma. |
Cancer Treat Res 1993, 62: 85 |
|
| Bielack S, Bieling P, Fuchs N, Winkler K |
Bone tumors in children. |
Kinderkrankenschwester 1993, 12: 114 |
|
| Bielack S, Beck J, Winkler K |
Spätfolgen nach Krebsbehandlung im Kindesalter. |
Monatsschr Kinderheilkd 1995, 649 |
|
| Bielack S, Erttmann R |
Anthracycline-induced cardiotoxicity in children. |
Late Sequelae in Oncology 1995, 175 |
|
| Bielack S, Wulff B, Delling G, Göbel U, Kotz R, Ritter J, Winkler K |
Osteosarcoma of the trunk treated by multimodal therapy. |
Med Pediatr Oncol 1995, 24: 6 |
|
| Bielack S, Erttmann R, Kempf-Bielack B, Winkler K |
Impact of scheduling on toxicity and clinical efficacy of doxorubicin: what do we know in the mid-nineties? |
Eur J Cancer 1996, 32A: 1652 |
|
| Bielack S, Kempf-Bielack B, Winkler K |
Osteosarcoma. |
J Clin Oncol 1996, 14: 683 |
|
| Bieling P, Rehan N, Winkler P, Helmke K, Maas R, Fuchs N, Bielack S, Heise U, Jürgens H, Treuner J, Romanowski R, Exner U, Kotz R, Winkler K |
Tumor size and prognosis in aggressively treated osteosarcoma. |
J Clin Oncol 1996, 14: 848 |
|
| Bielack S, Beron G, Winkler K |
Influence of methotrexate dose intensity on outcome of patients with high grade osteogenic osteosarcoma. |
Cancer 1997, 80: 516 |
|
| Bielack S, Kempf-Bielack B, Heise U, Schwenzer D, Winkler K |
Combined modality treatment for osteosarcoma occurring as a second malignant disease. Cooperative German-Austrian-Swiss Osteosarcoma Study Group. |
J Clin Oncol 1999, 17 |
|
| Bielack S, Kempf-Bielack B, Schwenzer D, Birkfellner T, Delling G, Ewerbeck V, Exner G, Fuchs N, Göbel U, Graf N, Heise U, Helmke K, von Hochstetter A, Jürgens H, Maas R, Munchow N, Salzer-Kuntschik M, Treuner J, Veltmann U, Werner M, Winkelmann W, Zoubek A, Kotz R |
Neoadjuvant therapy for localized osteosarcoma of extremities. Results from the Cooperative osteosarcoma study group COSS of 925 patients. |
Klin Pädiatr 1999, 211: 260 |
|
| Bielack S, Schroeders A, Fuchs N, Bacci G, Bauer H, Mapeli S, Tomeno B, Winkler K |
Malignant fibrous histiocytoma of bone. |
Acta Orthop Scand 1999, 70: 353 |
|
| Bielack S, Flege S, Kempf-Bielack B |
Behandlungskonzept des Osteosarkoms. |
Onkologe 2000, 6: 747 |
|
| Bielack S, Kempf-Bielack B, Delling G, Exner G, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A, Jürgens H, Winkler K |
Prognostic factors in high-grade osteosarcoma of the extremities or trunk. |
J Clin Oncol 2002, 20: 776 |
|
| Bielack S, Hunold A, Kempf-Bielack B, Jürgens H |
Maligne Knochentumoren. |
Kinder- und Jugendmedizin 2003, 3: 13 |
|
| Bielack S, Rerin J, Dickerhoff R, Dilloo D, Kremens B, Von Stackelberg A, Vormoor J, Jürgens H |
Osteosarcoma after allogeneic bone marrow transplantation. A report of four cases from the Cooperative Osteosarcoma Study Group (COSS). |
Bone Marrow Transplant 2003, 31: 353 |
|
| Bielack S, Tabone M |
Osteosarcomas occurring as second malignant neoplasms. |
Radiother Oncol 2003, 68 |
|
| Bielack S, Jürgens H |
Surgical expertise and outcome in osteosarcoma trials. |
J Clin Oncol 2004, 22: 2511 |
|
| Bielack S, Machatschek J, Flege S, Jürgens H |
Delaying surgery with chemotherapy for osteosarcoma of the extremities. |
Expert Opin Pharmacother 2004, 5: 1243 |
|
| Bielack S, Paulussen M, Kohler G |
A patient with two Ewing's sarcomas with distinct EWS fusion transcripts. |
N Engl J Med 2004, 350: 1364 |
|
| Bielack S, Carrle D |
Diagnostik und multimodales Therapiekonzept des Osteosarkoms. |
ärztliches journal reise & medizin onkologie, Otto Hoffmanns Verlag GmbH 3/2007, S: 34 |
|
| Bielack SS, Carrle D |
State-of-the-art approach in selective curable tumors: bone sarcoma. |
Annals of oncology 2008, 19 Suppl 7:vii155 |
|
| Bielack SS, Marina N, Ferrari S, Helman LJ, Smeland S, Whelan JS, Reaman GH |
Osteosarcoma: the same old drugs or more? |
Journal of clinical oncology 2008, 26: 3102-3; author reply 3104 |
|
| Bielack S |
Pediatric extraskeletal osteosarcoma. |
Pediatric radiology 2008, 38: 1033 |
|
| Bielack S |
Pediatric extraskeletal osteosarcoma. |
Pediatric radiology 2008, 38: 1033 |
|
| Bielack SS, Carrle D, Hardes J, Schuck A, Paulussen M |
Bone tumors in adolescents and young adults. [+] |
Current treatment options in oncology 2008, 9: 67 |
|
| OPINION STATEMENT: Bone tumors, particularly osteosarcomas and members of the Ewing Sarcoma Family of Tumors (ESFT), are typical malignancies of adolescents and young adults. Current diagnostic and therapeutic guidelines for patients of all ages were developed in this specific age group. The aim of bone sarcoma therapy should be to cure the patient from both the primary tumor and all (micro-)metastatic deposits while maintaining as much (extremity) function and causing as few treatment-specific late effects as possible. Bone sarcoma therapy requires close multidisciplinary cooperation. Usually, it consists of induction chemotherapy, followed by local therapy of the primary tumor (and, if present, primary metastases) and further, adjuvant chemotherapy. Local treatment for osteosarcoma should be surgery whenever feasible. Surgery is also gaining importance in ESFT, which was long considered a domain of radiotherapy. Modern reconstructive techniques continue to expand the indications for limb salvage, particularly for patients who have not yet reached skeletal maturity. Treatment within the framework of prospective, multi-institutional trials should be considered standard of care not only for children, but also for affected adolescents and (young) adults. Such trials are essential in guaranteeing that all patients have access to appropriate care and that progress from biological studies can be translated into prognostic improvements without undue delay. The rarity of bone sarcomas increasingly requires trials to be multinational. |
| Bielack SS, Kempf-Bielack B, Branscheid D, Carrle D, Friedel G, Helmke K, Kevric M, Jundt G, Kühne T, Maas R, Schwarz R, Zoubek A, Jürgens H |
Second and subsequent recurrences of osteosarcoma: presentation, treatment, and outcomes of 249 consecutive cooperative osteosarcoma study group patients. [+] |
Journal of clinical oncology 2009, 27: 557 |
|
| PURPOSE: To evaluate patient and tumor characteristics, treatment, and outcomes in a large cohort of unselected patients with second and subsequent recurrences of osteosarcoma. PATIENTS AND METHODS: Two hundred forty-nine consecutive patients who had originally received combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group protocols and went on to develop a total of 409 second and subsequent osteosarcoma recurrences were analyzed for patient-, tumor-, and treatment-related factors and outcomes. RESULTS: Five-year overall and event-free survival rates were 16% and 9% for 249 second, 14% and 0% for 93 third, 13% and 6% for 38 fourth, and 18% and 0% for 14 fifth recurrences, respectively. The proportion of recurrences confined to the lungs decreased and the proportion of those with chest wall involvement increased with increasing numbers of recurrences. The duration of relapse-free intervals and the number of lesions at recurrence correlated with outcomes. While only one of 205 patients with rerecurrence survived past 5 years without surgical remission, 5-year overall and event-free survival rates were 32% and 18% for 119 second, 26% and 0% for 45 third, 28% and 13% for 20 fourth, and 53% and 0% for five fifth recurrences, respectively, in which a renewed surgical remission was achieved. The use of chemotherapy correlated with longer survival in patients without surgical remissions. CONCLUSION: To our knowledge, this is the first report of survival estimates derived from large cohorts of unselected patients with second and subsequent osteosarcoma recurrences. It confirms the overwhelming importance of surgical clearance. Prognostic indicators after rerecurrences resemble those known from first recurrence. The exact role of re-treatment with chemotherapy, particularly in the adjuvant situation, remains to be defined. |
| Bielack SS, Franke M |
Re: Late recurrence in pediatric cancer: a report from the childhood cancer survivor study. |
Journal of the National Cancer Institute 2010, 102: 828; author reply 828 |
|
| Bielack SS |
Osteosarcoma: time to move on? |
European journal of cancer 2010, 46: 1942 |
|
| Bielack S, Jürgens H, Jundt G, Kevric M, Kühne T, Reichardt P, Zoubek A, Werner M, Winkelmann W, Kotz R |
Osteosarcoma: The COSS Experience. [+] |
Cancer treatment and research 2010, 152: 289 |
|
| COSS, the interdisciplinary Cooperative German-Austrian-Swiss Osteosarcoma Study Group, was founded in 1977 and has since registered some 3,500 bone sarcoma patients from over 200 institutions. For the purpose of the Pediatric and Adolescent Osteosarcoma Conference in Houston, March 2008, the outcomes of 2,464 consecutive patients with high-grade central osteosarcoma, who had been diagnosed between 1980 and 2005 and had been treated on neoadjuvant COSS protocols, were reviewed. Intended treatment had included surgery and multidrug chemotherapy, with high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide being used in most protocols. After a median follow-up of 7.31 years for 1,654 survivors, 5- and 10-year survival estimates were 0.748/0.695 for 2,017 patients with localized extremity tumors and 0.369/0.317 for 444 patients with axial tumors or/and primary metastases, respectively. Tumor response to preoperative chemotherapy was of independent prognostic significance. Over the years, there was a major shift from amputation towards limb-salvage. This development was least evident for patients below the age of 10. While survival expectancies improved from the first to the second half of the recruitment period, no further improvement was evident within the latter period. In the manuscript, the results described above are discussed based on the findings of the previous analyses of our group. |
| Bien E, Kazanowska B, Dantonello T, Adamkiewicz-Drozynska E, Balcerska A, Madziara W, Rybczynska A, Nurzynska-Flak J, Solarz E, Kurylak A, Zalewska-Szewczyk B, Krawczyk M, Izycka-Swieszewska E, Rapala M, Koscielniak E |
Factors predicting survival in childhood malignant and intermediate vascular tumors : retrospective analysis of the Polish and German cooperative paediatric soft tissue sarcoma study groups and review of the literature. [+] |
Ann Surg Oncol 2010, 17: 1878 |
|
| BACKGROUND: The rarity of malignant and intermediate vascular tumors in children means that little is known about their clinical course, optimal treatment, and variables predicting survival.
METHODS: A total of 32 children with malignant vascular tumors (14 angiosarcomas [AS], 5 epithelioid hemangioendotheliomas, and 13 intermediate vascular tumors, including other hemangioendotheliomas plus adult-type hemangiopericytomas), registered in the German and Polish Paediatric Soft Tissue Sarcomas Study Groups, were treated following the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, -86, -91, and -96 protocols.
RESULTS: Male sex, AS histology, tumor size >5 cm, and T2 invasiveness were independent predictors of inferior 5-year overall survival, while AS histology and T2 invasiveness were predictors of inferior 5-year event-free survival. AS histology was the most important negative prognostic factor for overall survival and event-free survival. Completeness of primary tumor excision was a good prognostic factor for survival in univariate, but not multivariate, analysis. Local therapy (radiotherapy and delayed surgery) were provided to the minority of patients (28% and 38%, respectively) late in the course of disease (after a mean of 9 and 6 months, respectively) and did not prevent local relapses. Response to systemic treatment was poor (44%) and did not prevent local and distant relapses.
CONCLUSIONS: The clinical course and outcome in childhood epithelioid HE seems to be similar to intravascular tumors and less aggressive than AS. RTX and delayed surgery should be performed more frequently and earlier in the disease course. An urgent need for modification of systemic therapy is needed because of the development of many metastatic and/or combined relapses and poor response to classic chemotherapy. The problem of effective therapy for childhood AS is the most appaling: 13 of 14 patients died of progression despite multimodal treatment. |
| Bielack S |
Osteosarkome. |
Leitlinie der Gesellschaft für Pädiatrische Onkologie und Hämatologie AWMF online, 2010 |
|
| Bielack SS, Marina N, Bernstein M |
High-intensity focused ultrasound (HIFU) is not indicated for treatment of primary bone sarcomas. |
Cancer 2011, 117: 2822, author reply 2822 |
|
| Biggar RJ, Frisch M, Goedert JJ |
Risk of cancer in children with AIDS. AIDS-Cancer Match Registry Study Group. |
JAMA 2000, 284: 205 |
|
| Biondi A, Valsecchi M, Seriu T, D'Aniello E, Willemse M, Fasching K, Pannunzio A, Gadner H, Schrappe M, Kamps W, Bartram C, van Dongen J, Panzer-Grumayer E |
Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group. |
Leukemia 2000, 14: 1939 |
|
| Biondi A, Baruchel A, Hunger S, Masera G, Schmiegelow K, Schrappe M, Pui CH |
The Eleventh International Childhood Acute Lymphoblastic Leukemia Workshop Report: Ponte di Legno, Italy, 6-7 May 2009. [+] |
Leukemia 2009, 23: 2318 |
|
| An international childhood acute lymphoblastic leukemia (ALL)working group was formed during the 27th annual meeting of the International Society of Pediatric Oncology in 1995. Since then, 10 workshops have been held to address many issues that help advance treatment outcome of childhood ALL but require international collaboration (Table 1). The group was fondly named after 'Ponte di Legno,' a place in Lombardy, Italy, because the first major workshop was held there. In celebration of the 10th anniversary of the first major meeting, the group returned to Ponte di Legno on 6 and 7 May 2009 for its 11th meeting (Figure 1). During the meeting, Professor Giuseppe Masera was honored for his vision and contributions to further develop the International-BFM study group and to co-found the Ponte di Legno working group. The meeting began with greetings by Professor Andrea Biondi. This report summarizes the data presented and the discussion in the meeting. |
| Biondi A, Schrappe M, De Lorenzo P, Castor A, Lucchini G, Gandemer V, Pieters R, Stary J, Escherich G, Campbell M, Li CK, Vora A, Aricò M, Röttgers S, Saha V, Valsecchi MG |
Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. [+] |
The lancet oncology 2012, 13: 936 |
|
| Trials of imatinib have provided evidence of activity in adults with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (ALL), but the drug's role when given with multidrug chemotherapy to children is unknown. This study assesses the safety and efficacy of oral imatinib in association with a Berlin-Frankfurt-Munster intensive chemotherapy regimen and allogeneic stem-cell transplantation for paediatric patients with Philadelphia-chromosome-positive ALL. |
| Bisogno G, Carli M, Stevens M, Oberlin O, Treuner J, Scarzello G, Colombatti R, De Zen L, Pinkerton C |
Intensive chemotherapy for children and young adults with metastatic primitive neuroectodermal tumors of the soft tissue. |
Bone Marrow Transplant 2002, 30: 297 |
|
| Bisogno G, Pilz T, Perilongo G, Ferrari A, Harms D, Ninfo V, Treuner J, Carli M |
Undifferentiated sarcoma of the liver in childhood. |
Cancer 2002, 94: 252 |
|
| Biskup W, Calaminus G, Schneider DT, Leuschner I, Göbel U |
Teratoma with malignant transformation: experiences of the cooperative GPOH protocols MAKEI 83/86/89/96. [+] |
Klinische Padiatrie 2006 Nov-Dec; 218: 303 |
|
| BACKGROUND: The designation of a teratoma with malignant transformation (TMT) refers to the occurrence of somatic non-germ cell malignancies within a teratoma. While TMT is a rare but well recognised phenomenon in adult germ cell tumors (GCT), data on TMT in pediatric GCTs are lacking. PATIENTS AND METHODS: Between 1982 and 2003, 641 patients with extracranial nontesticular pure teratoma (256 coccygeal, 246 ovarian, 139 other sites) were reported to the MAKEI protocols 83/86/89/96 by various, mainly German centres. Patients with teratoma and somatic malignancy were identified by database queries. Patients with malignant germ cell tumor components were excluded from this analysis. The clinical files were reviewed and re-evaluated centrally. Information was actualized by requisition to the participating hospitals. RESULTS: We identified nine patients (all female, age 0-39 years) meeting the histological criteria of TMT. Two patients had coccygeal teratomas and seven ovarian tumors. Carcinoma was the dominating malignancy (five of nine cases). Tumors with glial differentiation and embryonal tumors occurred in two cases each. Resection was performed in seven patients (including both coccygeal tumors) and adjuvant chemotherapy was administered in one of them. Two patients relapsed after resection, but both were cured with chemotherapy. Two patients suffered from advanced tumors and both were treated with primary chemotherapy. One patient was cured from the malignant component (astrocytoma), but the teratomatous components persisted. The other patient died as a result of progression of her malignant medulloepithelioma. CONCLUSIONS: Malignant transformation of pure teratomas constitutes a very rare entity in children and adolescents that is most commonly observed in postpubertal girls with ovarian teratoma. Compared to adult patients, similar malignant entities can be observed in association with teratoma. However, in our series, no sarcoma was diagnosed. In localised tumors, complete resection appears to be adequate, whereas chemotherapy should be considered in patients with R1- or R2-resection. Cisplatinum-based chemotherapy was effective as two of four relapsed patients survived tumor free. However, the ideal regimen has not yet been established and the known sensitivity of the histologic components to cytostatic drugs has to be considered in the choice of treatment. Further molecular biologic studies are necessary to understand the origin of these tumors. |
| Bisogno G, Ferrari A, Bien E, Brecht IB, Brennan B, Cecchetto G, Godzinski J, Orbach D, Reguerre Y, Stachowicz-Stencel T, Schneider DT |
Rare Cancers in Children - The EXPeRT Initiative: A Report from the European Cooperative Study Group on Pediatric Rare Tumors. [+] |
Klin Pädiatr 2012, 224: 416 |
|
| The low incidence and the heterogeneity of very rare tumors (VRTs) demand for international cooperation. In 2008, EXPeRT (European Cooperative Study Group for Pediatric Rare Tumors) was founded by national groups from Italy, France, United Kingdom, Poland and Germany. The first aims of EXPeRT were to agree on a uniform definition of VRTs and to develop the currently most relevant scientific questions. Current initiatives include international data exchange, retrospective and prospective studies of specific entities, and the development of harmonized and internationally recognized guidelines. Moreover, EXPeRT established a network for expert consultation to assist in clinical decision in VRTs. |
| Blanche S, Caniglia M, Girault D, Landman J, Griscelli C, Fischer A |
Treatment of hemophagocytic lymphohistiocytosis with chemotherapy and bone marrow transplantation: a single-center study of 22 cases. [+] |
Blood 1991, 78: 51 |
|
| Twenty-two children with hemophagocytic lymphohistiocytosis were treated with a chemotherapy regimen consisting of VP16-213, corticosteroids, and intrathecal methotrexate. A sustained clinical and biologic complete remission was obtained in 15 children and a partial remission in one child; six children died early of opportunistic infection (n = 4) or of disease progression (n = 2). Of the 16 children who were placed in first remission, 10 received maintenance chemotherapy alone, while six underwent bone marrow transplantation (HLA matched in five, HLA mismatched in one). Of the children who received chemotherapy alone, only two are in long-term remission after cessation of treatment. The remaining eight patients relapsed after a mean period of 5.4 months (range 2 to 8 months). Further treatment using the same regimen induced second remissions of short duration; death occurred after a median period of 2.3 months (range 0.5 to 6 months). A total of nine patients received allogeneic bone marrow transplantation (BMT). Among the six children transplanted in remission, four are in long-term unmaintained remission, 1 to 6 years after HLA-matched BMT. However, the relapse that occurred in one patient 1 year post BMT is difficult to interpret because the donor, the patient's 5-year-old sister, also developed the disease 1 year later. An HLA-nonidentical BMT resulted in unmaintained remission for 1 year, with autologous hematologic reconstitution followed by disease relapse. HLA-nonidentical BMT failed in three other patients with active disease at time of transplant. The poor long-term results of chemotherapy alone justify the use of related HLA-matched BMT in complete remission. |
| Blohm M, Vesterling-Horner D, Calaminus G, Göbel U |
Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age. |
Pediatr Hematol Oncol 1998, 15: 135 |
|
| Blohm M, Calaminus G, Gnekow A, Heidemann P, Bolkenius M, Weinel P, Schweinitz D, Ambros P, Schneider D, Harms D, Göbel U |
Disseminated choriocarcinoma in infancy is curable by chemotherapy and delayed tumour resection. |
Eur J Cancer 2001, 37: 72 |
|
| Blume KG, Forman SJ, Appelbaum F |
Thomas' Hematopoietic Cell Transplantation. |
Blackwell Scientific Publications, Cambridge 3. Aufl. 2004 |
|
| Boccon-Gibod L, Rey A, Sandstedt B, Delemarre J, Harms D, Vujanic G, de Kraker J, Weirich A, Tournade M |
Complete necrosis induced by preoperative chemotherapy in Wilms tumor as an indicator of low risk. |
Med Pediatr Oncol 2000, 34: 183 |
|
| Boccara O, Blanche S, de Prost Y, Brousse N, Bodemer C, Fraitag S |
Cutaneous hematologic disorders in children. [+] |
Pediatric blood & cancer 2012, 58: 226 |
|
| To determine and list the clinical and pathological features of cutaneous hematologic diseases in childhood. |
| Bode U, Hasan C |
Supportivmaßnahmen, akute Komplikationen und Notfälle, in Gutjahr P: Krebs bei Kindern und Jugendlichen. |
Deutscher Ärzte-Verlag Köln 5. Aufl. 2004, 173 |
|
| Boensch M, Oberthuer A, Fischer M, Skowron M, Oestreich J, Berthold F, Spitz R |
Quantitative real-time PCR for quick simultaneous determination of therapy-stratifying markers MYCN amplification, deletion 1p and 11q. [+] |
Diagnostic molecular pathology 2005, 14: 177 |
|
| Amplification of the oncogene MYCN as well as deletions in 1p and 11q are important prognostic and in part therapy-stratifying factors in human neuroblastoma. Due to the increasing clinical relevance of these molecular markers, accurate and fast assessment of the status of MYCN, 1p, and 11q is essential. As 2 techniques are recommended to avoid artefacts and to circumvent technical limitations, we developed a real-time q-PCR assay using genomic DNA from frozen and paraffin-embedded tissue as template as an alternative to LOH analyses and Southern blot (SB) and in addition to fluorescence in situ hybridization (FISH). Determination of deletion or amplification was achieved by comparing the copy number of a target gene (TG from the region of interest) to an unaffected reference gene (RG) within the same chromosome. PCR raw data were normalized to a serial dilution standard curve and a ratio TG/RG was created. The ratio to define a deletion was set as 0.5 (= expected ratio 1 TG copy/2 RG copies), the amplification threshold was set as >10.0. Data were compared to results obtained by FISH and were consistent in 10 of 13 (77%) tumors with deletion 1p, 18 of 20 (90%) with deletion 11q, 12 of 12 (100%) with MYCN amplification, and 146 of 151 (97%) samples without any aberration. Three tumors with aberrations in 1p and 2 tumors with aberrations in 11q were detectable by FISH but not by PCR. Three cases indicated a deletion 11q, 1 tumor a deletion 1p by PCR only. Specificity was 98% for 1p and MYCN each and 92% for 11q. Sensitivity was 77% for 1p, 90% for 11q, and 100% for MYCN. The discrepant results were mostly caused by heterogeneous cell populations of the investigated tissue; the use of real-time q-PCR for the detection of chromosomal aberrances in NB enables a fast and reliable assessment of the 3 most relevant chromosomal aberrations simultaneously. As the assay does not require reference tissue, can be performed with small amounts of DNA, and allows the investigation of paraffin-embedded material for the MYCN-status, it can be regarded alternative to LOH or SB analyses and in addition to FISH. |
| Bölling T, Schuck A, Willich N |
RiSK – Register zur Erfassung strahlentherapiebedingter Spätfolgen bei Kindern und Jugendlichen. |
WIR Informationsschrift der Aktion für krebskranke Kinder e.V. (Bonn) 2005, 4: 20 |
|
| Bölling T, Schuck A, Paulussen M, Dirksen U, Ranft A, Könemann S, Dunst J, Willich N, Jürgens H |
Whole lung irradiation in patients with exclusively pulmonary metastases of Ewing tumors. Toxicity analysis and treatment results of the EICESS-92 trial. [+] |
Strahlentherapie und Onkologie 2008, 184: 193 |
|
| BACKGROUND: In the European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) 92, whole lung irradiation (WLI) was performed in patients with primary lung metastases. This retrospective analysis evaluates the pulmonary function and the outcome of patients with exclusively pulmonary metastases. PATIENTS AND METHODS: Between 1990 and 1999, 99 patients were registered into the EICESS-92-study trial with exclusively pulmonary metastases of Ewing tumors. The multimodal treatment regimen included polychemotherapy and local therapy to the primary tumor. WLI was performed with a dose between 12-21 Gy. 70 patients were treated with WLI, 13 of them received a further boost to their primary tumor in the thorax up to a cumulative dose of 54 Gy. RESULTS: Pulmonary function tests were available for 37 patients treated with WLI (+/- boost). None, mild, moderate or severe pulmonary complications were seen in 43%, 29%, 21% and 7% of patients treated with WLI without further boost (median follow-up 25.2 months). Patients with an additional radiation boost or surgery to the thorax showed slightly higher rates of complications. Overall survival (OAS) showed a trend towards better results for patients with WLI (5-year-OAS: 0.61 for WLI vs. 0.49 for no WLI, p = 0.36). CONCLUSION: These data indicate a benefit and acceptable toxicity for WLI in the presented collective of patients. As long as there is no randomized prospective analysis, the present data confirm the indication for WLI in Ewing tumor patients with primary exclusively lung metastases. |
| Bölling T, Dirksen U, Ranft A, Ernst I, Jürgens H, Willich N |
Radiation toxicity following busulfan/melphalan high-dose chemotherapy in the EURO-EWING-99-trial: review of GPOH data. |
Strahlenther Onkol 2009, 185 Suppl 2: 21 |
|
| Bölling T, Ernst I, Pape H, Martini C, Rübe C, Timmermann B, Fischedick K, Kortmann RD, Willich N |
Dose-Volume Analysis of Radiation Nephropathy in Children: Preliminary Report of the RiSK Consortium. [+] |
International journal of radiation oncology, biology, physics 2010 Jul 15; |
|
| PURPOSE: To characterize kidney function in children and adolescents who had undergone radiation treatment that included parts of the kidney. METHODS AND MATERIALS: Patients receiving radiotherapy during childhood or adolescence were prospectively registered in Germany's Registry for the Evaluation of Side Effects after Radiation in Childhood and Adolescence (RiSK). Detailed information was recorded regarding radiation doses at the organs at risk since 2001 all over Germany. Toxicity evaluation was performed according to standardized Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: Up to May 2009, 1086 patients from 62 centers were recruited, including 126 patients (median age, 10.2 years) who underwent radiotherapy to parts of the kidneys. Maximal late toxicity (median follow-up 28.5 months in 74 patients) was characterized as Grade 0 (n = 65), 1 (n = 7) or 2 (n = 2). All patients with late effects had received potentially nephrotoxic chemotherapy. A statistically significant difference between patients with and without Grade 1 toxicity, revealing higher exposed kidney volumes in patients with toxicity, was seen for the kidney volume exposed to 20 Gy (V20; p = 0.031) and 30 Gy (V30; p = 0.003). CONCLUSIONS: Preliminary data indicate that radiation-induced kidney function impairment is rare in current pediatric multimodal treatment approaches. In the future, RiSK will be able to provide further detailed data regarding dose-volume effect relationships of radiation-associated side effects in pediatric oncology patients. |
| Bohn G, Welte K, Klein C |
Severe congenital neutropenia: new genes explain an old disease. [+] |
Current opinion in rheumatology 2007, 19: 644 |
|
| This review summarizes the recent advances in the diagnosis and molecular characterization of isolated and syndromal forms of severe congenital neutropenia. |
| Bolton-Maggs PH, Dickerhoff R, Vora AJ |
The nontreatment of childhood ITP (or . [+] |
Seminars in thrombosis and hemostasis 2001, 27: 269 |
|
| The management of childhood acute idiopathic thrombocytopenic purpura is controversial, with recent guidelines highlighting the lack of suitable evidence upon which to base management decisions. Three European centers have used an expectant policy and results over the past decade demonstrate that this is safe and convenient for the majority of children. Adequate parental education about the condition from an experienced specialist is essential, together with open access for children should they develop any problems. A clinical stratification of such patients must be incorporated into any future trials, together with quality of life assessment to discover the impact of restrictions on lifestyle, particularly in adolescents with chronic ITP who may need a different approach. |
| Bomelburg T, Roos N, von Lengerke H, Ritter J |
Invasive aspergillosis complicating induction chemotherapy of childhood leukaemia. |
Eur J Pediatr 1992, 151: 485 |
|
| Bonn BR, Rohde M, Zimmermann M, Krieger D, Oschlies I, Niggli F, Wrobel G, Attarbaschi A, Escherich G, Klapper W, Reiter A, Burkhardt B |
Incidence and prognostic relevance of genetic variations in T-cell lymphoblastic lymphoma in childhood and adolescence. [+] |
Blood 2013, 18; 121: 3153 |
|
| Probability of event-free survival (pEFS) in pediatric T-cell lymphoblastic lymphoma is about 80%, whereas survival in relapsed patients is very poor. No stratification criteria have been established so far. Recently, activating NOTCH1 mutations were reported to be associated with favorable prognosis, and loss of heterozygosity at chromosome 6q (LOH6q) was reported to be associated with increased relapse risk. The current project was intended to evaluate the prognostic effect of these markers. Mutations in hot spots of NOTCH1 and FBXW7 were analyzed in 116 patients. Concerning LOH6q status, 118 patients were investigated, using microsatellite marker analysis, in addition to an earlier reported cohort of 99 available patients. Ninety-two cases were evaluable for both analyses. All patients were treated with T-cell lymphoblastic lymphoma-Berlin-Frankfurt-Münster group (BFM)-type treatment. LOH6q was observed in 12% of patients (25/217) and associated with unfavorable prognosis (pEFS 27% ± 9% vs 86% ± 3%; P < .0001). In 60% (70/116) of the patients, NOTCH1 mutations were detected and associated with favorable prognosis (pEFS 84% ± 5% vs 66% ± 7%; P = .021). Interestingly, NOTCH1 mutations were rarely observed in patients with LOH in 6q16. Both prognostic markers will be used as stratification criteria in coming Non-Hodgkin Lymphoma-BFM trials. |
| Boos J, Real E, Schulze-Westhoff P, Pröbsting B, Wolff J, Jürgens H |
Pharmacokinetics of etoposide short-term infusions within the scope of the GPOH therapy protocol. |
Klin Pädiatr 1993, 205: 288 |
|
| Boos J, Krumpelmann S, Schulze-Westhoff P, Euting T, Berthold F, Jürgens H |
Steady-state levels and bone marrow toxicity of etoposide in children and infants. |
J Clin Oncol 1995, 13: 2954 |
|
| Boos J, Krümpelmann S, Schulze-Westhoff, Euting T, Berthold F, Jürgens H |
Steady-state levels and bone marrow toxicity of etoposide in children and infants. |
J Clin Oncol 1995, 13: 2954 |
|
| Boos J, Silies H, Hohenlöchter B, Jürgens H, Blaschke G |
Short-term versus continuous infusion. |
Eur J Cancer 1995, 31A: 2417 |
|
| Boos J, Schulze-Westhoff, Lanvers C, May-Manke A, Hohenlöchter B, Hempel G, Jürgens H |
Pharmacokinetics of antineoplastic drugs in in vitro assays. |
Med Pediatr Oncol 1996, 27 |
|
| Boos J, Hohenlochter B, Schulze-Westhoff P, Schiller M, Zimmermann M, Creutzig U, Ritter J, Jürgens H |
Intracellular retention of cytosine arabinoside triphosphate in blast cells from children with acute myelogenous and lymphoblastic leukemia. |
Med Pediatr Oncol 1996, 26: 397 |
|
| Boos J, Schiller M, Pröbsting B, Creutzig U, Ritter J |
Intracellular retention of cytosine-arabinoside-triphosphate in leukemic blast cells from children. |
Haematology and Blood Transfusion 1996, 37: 50 |
|
| Bopp A, Kameda G |
Unser Kind hat Krebs. |
Verlag Urachhaus 2011 |
|
| Borgmann A, Emminger W, Emminger-Schmidmeier W, Peters C, Gatterer-Menz I, Henze G, Gadner H |
Influence of fractionated total body irradiation on mucosal toxicity in intensified conditioning regimens for autologous bone marrow transplantation in pediatric cancer patients. |
Klin Pädiatr 1994, 206: 299 |
|
| Borgmann A, Hartmann R, Schmid H, Klingebiel T, Ebell W, Göbel U, Peters C, Gadner H, Henze G |
Isolated extramedullary relapse in children with acute lymphoblastic leukemia. |
Bone Marrow Transplant 1995, 15: 515 |
|
| Borgmann A, Schmid H, Hartmann R, Baumgarten E, Hermann K, Klingebiel T, Ebell W, Zintl F, Gadner H, Henze G |
Autologous bone-marrow transplants compared with chemotherapy for children with acute lymphoblastic leukaemia in a second remission. |
Lancet 1995, 346: 873 |
|
| Borgmann A, Baumgarten E, Schmid H, Döpfer R, Ebell W, Göbel U, Niethammer D, Gadner H, Henze G |
Allogeneic bone marrow transplantation for a subset of children with acute lymphoblastic leukemia in third remission. |
Bone Marrow Transplant 1997, 20: 939 |
|
| Borkhardt A, Cazzaniga G, Viehmann S, Valsecchi M, Ludwig W, Burci L, Mangioni S, Schrappe M, Riehm H, Lampert F, Basso G, Masera G, Harbott J, Biondi A |
Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster Study Group. |
Blood 1997, 90: 571 |
|
| Bornfeld N, Schuler A, Bechrakis N, Henze G, Havers W |
Preliminary results of primary chemotherapy in retinoblastoma. [+] |
Klin Pädiatr 1997, 209: 216 |
|
| BACKGROUND: Eye retention rates after external beam therapy for advanced retinoblastoma are close to 90% with very few ocular side effects like radiation retinopathy or radiation induced optic neuropathy. Late complications, however, comprise a sixfold increase of secondary non-ocular cancers like soft tissue sarcomas demanding alternative treatment options in the management of advanced retinoblastoma. PURPOSE: A phase I study on primary chemotherapy using vincristine, cyclophosphamide, etoposide and carboplatin in advanced bilateral retinoblastoma was undertaken to evaluate the potential of a treatment regimen not including external beam therapy. PATIENTS AND METHODS: 12 eyes with 17 tumors in 9 children were treated with primary chemotherapy as first treatment option with a mean follow-up of 16.7 months. Planned enucleation of a tumor containing eye was performed in 2 eyes. In one of these enucleated eyes no viable tumor cells were visible on histopathological examination while in the other eye marked tumor regression was detectable. Of the remaining 10 eyes clinical regression of the intraocular tumors was present in all eyes; on average the tumor size was reduced by 50% within 3-6 weeks. Most of the tumors showed a type I (cottage cheese) regression indistinguishable from regression patterns found after external beam radiotherapy. Ancillary treatments including laser photocoagulation, beta-ray brachytherapy, external beam radiotherapy and cryotherapy were performed in 15 out of the 17 tumors. CONCLUSION: Based on the results of this study and on the results published by others primary chemotherapy may result in the same eye retention rate as conventional external beam therapy avoiding the unacceptable high rate of secondary non-ocular cancers in the latter. A prospective study to be undertaken by the GPOH (Gesellschaft für Pädiatrische Onkologie und Hämatologie) and the RG (Retinologische Gesellschaft) is planned to further evaluate this new and promising approach. |
| Borowski A, van Valen, Ulbrecht M, Weiss E, Blasczyk R, Jürgens H, Göbel U, Schneider E |
Monomorphic HLA class I-(non-A, non-B) expression on Ewing's tumor cell lines, modulation by TNF-alpha and IFN-gamma. |
Immunobiology 1999, 200: 1 |
|
| Borgmann A, Baldy C, Von Stackelberg A, Beyermann B, Fichtner I, Nürnberg P, Henze G |
Childhood all blasts retain phenotypic and genotypic characteristics upon long-term serial passage in NOD/SCID mice. |
Pediatr Hematol Oncol 2000, 17: 635 |
|
| Borkhardt A, Wuchter C, Viehmann S, Pils S, Teigler-Schlegel A, Stanulla M, Zimmermann M, Ludwig W, Janka-Schaub G, Schrappe M, Harbott J |
Infant acute lymphoblastic leukemia - combined cytogenetic, immunophenotypical and molecular analysis of 77 cases. |
Leukemia 2002, 16: 1685 |
|
| Borgmann A, Von Stackelberg A, Hartmann R, Ebell W, Klingebiel T, Peters C, Henze G |
Unrelated donor stem cell transplantation compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission. |
Blood 2003, 101: 3835 |
|
| Borowski A, Dirksen U, Lixin L, Shi, RL, G÷bel U, Schneider, EM |
Structure and function of ETAA16: a novel cell surface antigen in Ewing's tumours. [+] |
Cancer Immunol Immunother Vol.55; 2006, 363 |
|
| Immunoscreening of an Ewing's family of tumour (EFT)-derived cDNA library using formerly described EFT-specific antibodies led to the isolation of a 3.5 kb cDNA, named Ewing's tumour-associated antigen 16 (ETAA16). The ETAA16 cDNA shows no homology to any functionally characterised human gene. Only a bovine cDNA expressed in bovine testis and hepatocytes is functionally characterised as it encodes for a junction plaque associated protein and showed a homology of 69.9% at amino acid level to ETAA16. The human cDNA encodes for a 926 amino acid tumour antigen with a calculated molecular weight of 103 kDa. The epitope of the ETAA16-specific antibody, Ak16, covers the central region of the protein which is part of an extra cellular domain. The human ETAA16 gene locus has been assigned to chromosome 2p13-15 by FISH analyses and is confirmed by the human genome sequencing project. As demonstrated by flow cytometry, the cell surface expression of ETAA16 antigen is restricted to ET cell lines and not expressed on other small blue round cell tumours or other kind of tumour. RT-PCR analysis revealed a high expression of ETAA16 in brain, liver and kidney while lung and heart were negative. Immunohistochemistry showed an intracellular expression of ETAA16 in different kind of non-Ewing tumour tissues. These results suggest that ETAA16 may function as a tumour-specific cell surface antigen in EFTs. |
| Borgna-Pignatti C |
Modern treatment of thalassaemia intermedia. [+] |
British journal of haematology 2007, 138: 291 |
|
| The term thalassaemia intermedia includes a large spectrum of conditions of varying severity. Blood transfusion and chelation are necessary in some patients, especially during childhood, in order to promote growth and prevent bone deformities. Alloimunisation, however, is frequent and can be difficult to control. Splenectomy is usually needed at some time because of hypersplenism and mechanical encumbrance. Reactivation of HbF is possible only in a small proportion of patients: hydroxycarbamide (also known as hydroxyurea) appears to be the most effective drug for this purpose. Antioxidant agents, although theoretically useful, do not improve haemoglobin levels. Stem cell transplantation is an option limited to the severe forms. Gene therapy and other molecular approaches are subjects of intense study. Numerous complications, including pulmonary hypertension, thrombotic events, pseudoxanthoma elasticum and osteoporosis, have been described and all contribute to complicate the treatment of a disease that represents a significant burden for the patients and their families. |
| Borgmann A, Zinn C, Hartmann R, Herold R, Kaatsch P, Escherich G, Möricke A, Henze G, von Stackelberg A, ALL-REZ BFM Study Group |
Secondary malignant neoplasms after intensive treatment of relapsed acute lymphoblastic leukaemia in childhood. [+] |
European journal of cancer (Oxford, England : 1990) 2008, 44: 257 |
|
| PURPOSE: To investigate the cumulative incidence of and the risk factors for developing second malignant neoplasms (SMN) in children and adolescents following treatment for relapse of acute lymphocytic leukaemia (ALL). METHODS: Patients (1376) up to 18 years of age with first relapse of non-B-cell ALL were treated and achieved a 2nd complete remission (CR). The treatment followed trial protocol in five consecutive multicentre trials of the ALL-REZ BFM Study Group between March 1983 and December 2001. The incidence of SMN was analysed, correlated with clinical and therapeutic parameters, and compared to the age-specific incidence rates of cancers as cited in German cancer registries. RESULTS: Out of the 1376 patients 21 were diagnosed with SMN including non-lymphoblastic leukaemia/myelodysplastic syndrome (n=6), osteo-/Ewing's-/fibroblastic sarcoma (n=4), B-cell ALL/lymphoma (n=2), thyroid carcinoma (n=2), basal cell carcinoma, adeno carcinoma, squamous cell carcinoma, meningioma, malignant histiocytosis, glioblastoma and anaplastic astrocytoma (n=1 each). The overall cumulative risk of SMN at 15 years (median follow-up of 13.1 years) was 1.26%+/-0.38% (SE). SMN was found to be significantly associated with stem cell transplantation (SCT), and high cumulative doses of cranial irradiation, etoposide and cyclophosphamide. In multivariate analysis etoposide (VP16) and cyclophophamide (CY) were found to be independently associated with SMN (p=0.047 and 0.002). Compared to the incidence of neoplasm in the age-matched population, there was a 10-fold increase of neoplasia. CONCLUSIONS: Despite repeated exposure to intense frontline and relapse treatment (including multiagent chemotherapy, cranial irradiation and stem cell transplantation in some patients) the cumulative incidence of SMN was unexpectedly low, though significantly higher than in the general age-matched population. The association of SMN to SCT seemed to be a secondary effect at least partially mediated by exposure to high doses of VP16 and CY given for conditioning therapy. |
| Bornfeld N, Holdt M, Biewald E, Wieland R, Eggert A, Göricke S, Lohmann D |
[New developments in molecular genetics and treatment of retinoblastoma]. [+] |
Klinische Monatsblatter fur Augenheilkunde 2011, 228: 593 |
|
| Retinoblastomas are the most frequent primary malignant intraocular tumours worldwide. Conventional and new treatment modalities have significantly improved the chance for survival and preservation of vision. The armamentarium of treatment modalities has been broadened recently by new techniques like intraarterial chemotherapy, which still has to be considered as experimental since long-term follow-up results are not yet available. The excellent prognosis for retinoblastomas in countries with a well developed health system is contrasted by the miserable prognosis for retinoblastomas in developing countries, which must be changed by a joint effort of all centres. |
| Borgmann-Staudt A, Rendtorff R, Reinmuth S, Hohmann C, Keil T, Schuster FR, Holter W, Ehlert K, Keslova P, Lawitschka A, Jarisch A, Strauss G |
Fertility after allogeneic haematopoietic stem cell transplantation in childhood and adolescence. [+] |
Bone marrow transplantation 2012, 47: 271 |
|
| Infertility is a major late effect in patients receiving haematopoietic stem cell transplantation (HSCT). The aim of this study was to determine the proportion of patients having fertility impairment after allogeneic HSCT in childhood/adolescence and to identify the potential risk factors. Treatment and fertility data of paediatric patients with malignant and non-malignant diseases treated with allogeneic HSCT between 2000 and 2005 were collected from seven European centres. Data were obtained for 138 female and 206 male patients after a median follow-up of 6 years (range 3-12). The patients' median age was 13 years (range 4-28) at the time of HSCT and 19 (range 12-35) years at the time of the enquiry. Seven children were born to the overall group, all at term and healthy. Fertility impairment was suspected in 69% males and 83% females. Start of treatment at age 13 years was a risk factor in females (odds ratio (OR) 4.7; 95% confidence interval (CI), 1.5 to 14.9), whereas pre-pubertal therapy was a risk factor in males (OR 0.4; 95% CI, 0.2 to 0.8). The major treatment-related risk factors were BU in females (OR 47.4; 95% CI, 5.4 to 418.1) and TBI in males (OR 7.7; 95% CI, 2.3 to 25.4). In light of the significant proportion of HSCT patients reviewed with impaired fertility, fertility conservation procedures should be considered for all patients undergoing HSCT, particularly those receiving TBI or BU-based preparative regimens. |
| Bourne JP, Geyer R, Berger M, Griffin B, Milstein J |
The prognostic significance of postoperative residual contrast enhancement on CT scan in pediatric patients with medulloblastoma. [+] |
J Neurooncol 1992, 14: 263 |
|
| The clinical and therapeutic features of 20 patients with medulloblastoma treated at Children's Hospital and Medical Center, Seattle, from 1980 to 1987, were retrospectively analyzed with regard to prognosis. The overall actuarial 5-year survival rate was 63%, with 57% of patients free from recurrence at 5 years. Residual contrast enhancement on CT scans taken immediately postoperatively was associated with a significantly decreased 5-year recurrence-free survival rate; the 5-year recurrence-free survival rate was 100% for those patients without post-operative residual enhancement compared to 41% for those patients with residual enhancement. A high risk group of patients with residual contrast enhancement persisting one year following diagnosis was identified. No patient in this group survived without disease progression. Other factors, including sex, age at diagnosis, evidence of tumor dissemination, or extent of surgical resection as reported by the neurosurgeon, did not significantly influence prognosis. |
| Bourquin JP, Subramanian A, Langebrake C, Reinhardt D, Bernard O, Ballerini P, Baruchel A, Cave H, Dastugue N, Hasle H, Kaspers GL, Lessard M, Michaux L, Vyas P, van Wering E, Zwaan CM, Golub TR, Orkin SH |
Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling. [+] |
Proceedings of the National Academy of Sciences of the United States of America 2006, 103: 3339 |
|
| Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples. We found that non-DS-AMKL samples cluster in two groups, characterized by differences in expression of HOX/TALE family members. Both of these groups are distinct from DS-AMKL, independent of chromosome 21 gene expression. To explore alterations of the GATA1 transcriptome, we used cross-species comparison with genes regulated by GATA1 expression in murine erythroid precursors. Genes repressed after GATA1 induction in the murine system, most notably GATA-2, MYC, and KIT, show increased expression in DS-AMKL, suggesting that GATA1s fail to repress this class of genes. Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21. Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL. Our results identify relevant signatures for distinct AMKL entities and provide insight into gene expression changes associated with these related leukemias. |
| Boztug K, Welte K, Zeidler C, Klein C |
Congenital neutropenia syndromes. [+] |
Immunology and allergy clinics of North America 2008, 28: 259-75, vii-viii |
|
| Congenital neutropenia syndromes comprise a heterogeneous group of inherited disorders. Hereditary conditions associated with low neutrophil counts are persistent and need to be differentiated from neutropenia secondary to autoimmune processes or other pathologic conditions, such as myelodysplasia or leukemia. Clinically, congenital neutropenia is characterized by recurrent bacterial infections. Recently, several novel genetic defects were described in patients with congenital neutropenia, shedding light on the pathophysiology of these rare diseases. |
| Boxberger N, Redlich A, Böger C, Leuschner I, von Schweinitz D, Dralle H, Vorwerk P |
Neuroendocrine tumors of the appendix in children and adolescents. [+] |
Pediatric blood & cancer 2012, |
|
| BACKGROUND: Neuroendocrine tumors (NET) of the appendix in children and adolescents are rare and mostly detected postoperatively by a histopathological examination. Since the malignant potential of these tumors remains unclear, therapeutic recommendations are not evidence based. The Society of Pediatric Oncology and Hematology (GPOH) has prospectively registered and followed children with appendical NET since 1997 (GPOH-MET trial). The objective of this study was to critically evaluate the therapeutic recommendations for appendical NET in children. PROCEDURE: Clinical data of 237 children with appendical NET were prospectively analyzed. RESULTS: The mean age at presentation was 13.0 years, while the mean follow-up time was 2.9 (0.0-12.8) years. The majority of tumors (70.9%) were located at the apex, and were smaller than or equal to 10 mm (72.7%). Tumor size was directly correlated with age. A second operation or primary lymph node sampling was done in 25.3% (N = 60) of the patients, and infiltration of the lymph nodes by tumor cells was found in nine of these patients (15%). All 237 patients are alive without tumor symptoms. CONCLUSIONS: ROC analysis and subsequent calculations identified a tumor size of >15 mm as the optimal cut-off point for the prediction of metastatic spread into the lymph system, with a sensitivity of 77.8% and a specificity of 66.7%. Therefore, secondary right hemicolectomy in completely removed appendical NET is recommended only in tumors >15 mm in size. For incompletely removed tumors ≤15 mm a local follow-up resection with lymph node sampling is recommended. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. |
| Boztug K, Welte K, Zeidler C, Klein C |
Congenital neutropenia syndromes. [+] |
Immunology and allergy clinics of North America 2008, 28: 259-75, vii-viii |
|
| Congenital neutropenia syndromes comprise a heterogeneous group of inherited disorders. Hereditary conditions associated with low neutrophil counts are persistent and need to be differentiated from neutropenia secondary to autoimmune processes or other pathologic conditions, such as myelodysplasia or leukemia. Clinically, congenital neutropenia is characterized by recurrent bacterial infections. Recently, several novel genetic defects were described in patients with congenital neutropenia, shedding light on the pathophysiology of these rare diseases. |
| Brasme JF, Chalumeau M, Doz F, Lacour B, Valteau-Couanet D, Gaillard S, Delalande O, Aghakhani N, Sainte-Rose C, Puget S, Grill J |
Interval between onset of symptoms and diagnosis of medulloblastoma in children: distribution and determinants in a population-based study. [+] |
European journal of pediatrics 2012, 171: 25 |
|
| Hospital-based studies have reported long delays in the diagnosis of paediatric brain tumours. Our objective was to describe the duration between onset of symptoms and diagnosis of medulloblastoma in children and study their clinical determinants in a population-based study. This retrospective cohort study included all paediatric medulloblastoma from a region of France from 1990 to 2005. The median interval from symptom onset until diagnosis for these 166 patients was 65 days and did not decrease during the study period. The most frequent manifestations were: vomiting (88%), headaches (79%), psychomotor regression (60% of children under 3 years), psychological symptoms (27%), strabismus (26%), and asthenia (25%). For one third of the children under 3 years, the diagnosis was made only after life-threatening signs of intracranial hypertension appeared. The prediagnosis interval was significantly longer (median 91 vs. 60 days, p = 0.001) in children with psychological symptoms (27%). Causes for intervals that exceeded the median (65 days) included inconsistent (25%) or late (36%) combination of headaches and vomiting, a period of spontaneous symptom remission (14%-20%), no (24%) or late (57%) neurological signs, psychological symptoms (35%), and a normal neurological examination (27%). Time to medulloblastoma diagnosis in children remains fairly long, despite advances in imaging. Primary-care physicians must be suspicious not only of suggestive neurological signs, but also of non-specific symptoms that persist or are multiple. A meticulous neurological examination and cerebral imaging for such patients might facilitate earlier diagnosis. |
| Breu H, Schellong G, Grosch-Wörner I, Jobke A, Riehm H, Ritter J, Treuner J, Schwarze E, Wannenmacher M |
Abgestufte Chemotherapie und reduzierte Strahlendosis beim Morbus Hodgkin im Kindesalter - Ein Bericht über 170 Patienten der kooperativen Therapiestudie HD-78. |
Klin Pädiatr 1982, 194: 233 |
|
| Brenner H, Kaatsch P, Burkhardt-Hammer T, Harms D, Schrappe M, Michaelis J |
Long-term survival of children with leukemia achieved by the end of the second millennium. |
Cancer 2001, 92: 1977 |
|
| Brennan BM, Shalet SM |
Endocrine late effects after bone marrow transplant. |
British J Haematol 2002, 118: 58 |
|
| Brecht I, Treuner J |
Weichteilsarkome im Kindes- und Jugendalter. Erfahrungen der Cooperativen Weichteilsarkom-Studie (CWS). Handchirurgie, Mikrochirurgie, Plastische Chirurgie. |
in press 2004 |
|
| Brecht IB, Graf N, Schweinitz D, Frühwald MC, Bielack SS, Schneider DT |
Networking for children and adolescents with very rare tumors: foundation of the GPOH Pediatric Rare Tumor Group. [+] |
Klinische Padiatrie 2009, 221: 181 |
|
| In comparison to cancer in adults, virtually all cancers of childhood and adolescence are rare. Nevertheless, there is a rather ill-defined group of tumors that are not only exceptionally rare but also do not fall into the major clinical categories of childhood cancers. Thus, a substantial proportion of these exceptionally rare tumors are not registered within clinical registries or prospective therapy optimization studies. Only recently, major attention has been drawn to the diagnostic assessment and treatment of children and adolescents with such orphan diseases. In 2006, the RARE TUMOR GROUP has been established within the German Society of Pediatric Oncology and Hematology (GPOH). This working group includes experts from Pediatric Oncology, Pediatric Surgery, Pediatric Pathology, Medical, Dermatologic and Radiation Oncology as well as Pediatric Epidemiology. The major aim of the rare tumor group is to integrate these patients into the diagnostic and therapeutic network successfully established in the pediatric oncologic society. Thus, the group aims at fostering the exchange of experience in the treatment of rare tumors between medical centers and to include patients in the diagnostic and therapeutic reference network. In addition, an information platform shall be established that will be accessible to treating physicians, patients and their parents. More information and better registration shall be established by active data accrual on a regular basis and by the implementation of a data base including diagnostic and therapeutic data of patients with rare tumors. These efforts as presented in this article as well as an intensified international collaboration will allow us to provide children and adolescents with rare tumors the best possible care. |
| Brecht IB, Schneider DT, Klöppel G, von Schweinitz D, Barthlen W, Hamre MR |
Malignant Pancreatic Tumors in Children and Young Adults: Evaluation of 228 Patients Identified through the Surveillance, Epidemiology, and End Result (SEER) Database. [+] |
Klinische Padiatrie 2011, 223: 341 |
|
| Malignant pancreatic tumors are rare in young patients, few epidemiologic data are available. We reviewed prognostic factors and outcome of 228 patients <30 years with malignant pancreatic tumors identified through the U.S. National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) Public-use Database from 1973 to 2004.Cases were grouped using the ICD-O-3. 5-year overall survival (OAS) was assessed by gender, ethnicity, SEER stage, and 5-year age intervals using univariate and Cox regression analysis.228 patients with malignant pancreatic tumors were identified, resulting in an incidence of 0.46/million (100 carcinomas, 85 endocrine tumors, 8 solid pseudopapillary neoplasms (SPN), 11 pancreatoblastomas) in the USA. OAS was worse in males than females (37% vs. 55%, p=0.005). OAS according to stage was 87%, 68%, 21% for local (n=54), regional (n=42), distant metastatic disease (n=108), respectively. OAS of patients with carcinoma was 33%, endocrine tumors 58%, SPNs 88%, pancreatoblastomas 66%. Cox regression revealed stage (p=< 0.001), histology (p=< 0.001), age group (p=0.05) to be independent prognostic factors.Malignant pancreatic tumors are extremely rare in children and young adults. Entities change over the age groups towards more carcinomas with worse outcome in older patients. Tumor stage, histology and age group are important predictors for outcome. International collaboration is needed to learn more about pediatric pancreatic tumors. |
| Breuer S, Preuner S, Fritsch G, Daxberger H, Koenig M, Poetschger U, Lawitschka A, Peters C, Mann G, Lion T, Matthes-Martin S |
Early recipient chimerism testing in the T- and NK-cell lineages for risk assessment of graft rejection in pediatric patients undergoing allogeneic stem cell transplantation. [+] |
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 2012, 26: 509 |
|
| Timely diagnosis of impending graft rejection is crucial for effective therapeutic intervention after allogeneic hematopoietic stem cell transplantation (SCT). We have investigated the predictive potential of early leukocyte subset-specific chimerism for graft loss in children undergoing SCT. In total, 192 pediatric patients transplanted for the treatment of malignant and non-malignant diseases after reduced-intensity or myeloablative conditioning were investigated. Surveillance of lineage-specific chimerism was initiated upon first appearance of leukocyte counts amenable to cell sorting. Graft rejection occurred in 23 patients between 24 and 492 days post-transplant (median 63 days). The first chimerism analysis of T and NK cells performed at a median of 20 days after SCT identified three different risk groups that were independent from the conditioning regimen: recipient chimerism (RC) levels in T cells below 50% indicated a very low risk of rejection (1.4%), whereas high levels of RC (>90%) both in T and NK cells heralded graft loss in the majority of patients (90%) despite therapeutic interventions. RC >50% in T cells and ≤90% in NK cells defined an intermediate-risk group in which timely immunotherapy frequently prevented rejection. Early assessment of T- and NK-cell chimerism can therefore be instrumental in the risk assessment and therapeutic management of imminent graft rejection. |
| Brecht IB, Agaimy A, Besendörfer M, Carbon R, Thiel FC, Rompel O, Osinski D, Langer T, Metzler M, Holter W |
Malignant Peritoneal Mesothelioma in a 16-Year-Old Girl: Presentation of a Rare Disease. [+] |
Klinische Padiatrie 2012, 224: 170 |
|
| Malignant peritoneal mesothelioma is extremely rarely seen in young patients.A 16 year-old girl presented with appendicitis-like acute abdominal pain. Intra-operatively, multiple confluent peritoneal nodules were seen on the entire greater omentum and in the pelvis infiltrating the uterus and both ovaries. Biopsies were obtained and interpreted as serous ovarian carcinoma. Radical surgical resection and hyperthermic intraperitoneal chemotherapy -(HIPEC) with carboplatin was performed and followed by 2 cycles of carboplatin/paclitaxel. Histological reevaluation showed characteristic features of epithelioid peritoneal mesothelioma and ruled out serous ovarian cancer. Therapy was continued with 6 cycles of pemetrexed/cisplatin.3 months after end of chemotherapy vital tumor tissue was found in the recess behind the liver, which could be resected completely. The patient is currently disease-free 17 months after initial diagnosis.Malignant peritoneal mesothelioma in young female patients might be under-recognized and possibly misdiagnosed as ovarian serous carcinoma in some cases. International and interdisciplinary cooperation is necessary in order to provide evidence based guidelines for diagnosis and treatment in the future. |
| Briggs BJ, Dickerman JD |
Bleeding disorders in Noonan syndrome. [+] |
Pediatric blood & cancer 2012, 58: 167 |
|
| Noonan Syndrome (NS) is a common genetic disease with multiple organ defects including bleeding disorders, which was last reviewed in 1997. Since then significant information has been acquired regarding bleeding problems in NS, specifically on the underlying genetics. Associations between mutated genes and bleeding disorders are reviewed along with prevalence and underlying etiologies. Between 50-89% of NS patients will have a bleeding disorder and since a significant number will require surgery it is important to identify which ones are at risk prior to their procedure. Recommendations regarding screening for bleeding disorders and their treatment are discussed. Pediatr Blood Cancer 2012; 58: 167-172. © 2011 Wiley Periodicals, Inc. |
| Brodeur G, Pritchard J, Berthold F, Carlsen N, Castel V, Castelberry R, De Bernardi B, Evans A, Favrot M, Hedborg F, |
Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. |
J Clin Oncol 1993, 11: 1466 |
|
| Brodeur G, Pritchard J, Berthold F, Carlsen N, Castel V, Castelberry R, De Bernardi B, Evans A, Favrot M, Hedborg F, |
Revisions of the international criteria for neuroblastoma diagnosis, staging and response to treatment. |
Prog Clin Biol Res 1994, 385: 363 |
|
| Broadbent V, Gadner H |
Current therapy for Langerhans cell histiocytosis. |
Hematol Oncol Clin North Am 1998, 12: 327 |
|
| Broniscer A, Gajjar A |
Supratentorial high-grade astrocytoma and diffuse brainstem glioma: two challenges for the pediatric oncologist. |
Oncologist 2004, 9: 197-206. Review |
|
| Broniscer A, Nicolaides TP, Dunkel IJ, Gardner SL, Johnson J Jr, Allen JC, Sposto R, Finlay JL |
High-dose chemotherapy with autologous stem-cell rescue in the treatment of patients with recurrent non-cerebellar primitive neuroectodermal tumors. [+] |
Pediatr Blood Cancer 2004, 261 |
|
| BACKGROUND: Recurrent non-cerebellar primitive neuroectodermal tumors (PNETs) carry a dismal prognosis when treated with conventional chemotherapy alone. XSWe tested the efficacy of high-dose chemotherapy (HDC) followed by autologous stem-cell rescue (ASCR) in this setting. PROCEDURE: Eligibility mandated either minimal residual disease or evidence of chemosensitivity before HDC. Conditioning consisted of carboplatin (CBDCA) (500 mg/m(2) or AUC = 7 mg/ml min using the Calvert formula) on days -8 to -6, thiotepa (300 mg/m(2)), and etoposide (250 mg/m(2)) on days -5 to -3. Irradiation was given post HDC selectively. RESULTS: Among 17 patients treated in this study, there were eight pineoblastoma(s) (pineo), seven cortical PNETs, and two arising elsewhere. Relapse was either local (nine) or metastatic to the brain (four) or spine (four). Two patients received HDC as the sole therapy for recurrence; additionally, eight underwent surgical debulking before HDC, and nine received irradiation, including six after HDC. Median age at ASCR was 3.9 years. Two patients died of toxicity (11%) and ten experienced tumor relapse (range: 23-361 days post ASCR). Five patients with cortical PNETs remain alive disease-free (median follow-up: 8.3 years); four of them received irradiation post HDC. The difference in 5-year event-free survival (EFS) between patients with pineo and other supratentorial PNETs was significant (0 vs. 62.5 +/- 17%, P = 0.0065). Both surgery at relapse and irradiation post HDC were favorable prognostic factors (P = 0.006 and 0.01, respectively). CONCLUSIONS: Patients with recurrent cortical PNETs can be cured with this strategy. Surgical debulking before, and irradiation after HDC play an important role in treatment success. Copyright 2003 Wiley-Liss, Inc. |
| Brugières L, Le Deley MC, Rosolen A, Williams D, Horibe K, Wrobel G, Mann G, Zsiros J, Uyttebroeck A, Marky I, Lamant L, Reiter A |
Impact of the Methotrexate Administration Dose on the Need for Intrathecal Treatment in Children and Adolescents With Anaplastic Large-Cell Lymphoma: Results of a Randomized Trial of the EICNHL Group. [+] |
Journal of clinical oncology 2009, 27: 897 |
|
| PURPOSE To compare the efficacy and safety of two methotrexate doses and administration schedules in children with anaplastic large-cell lymphoma (ALCL). PATIENTS AND METHODS This randomized trial for children with ALCL was based on the Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Muenster 90 (NHL-BFM90) study protocol and compared six courses of methotrexate 1 g/m(2) over 24 hours and an intrathecal injection (IT) followed by folinic acid rescue at 42 hours (MTX1 arm) with six courses of methotrexate 3 g/m(2) over 3 hours followed by folinic acid rescue at 24 hours without IT (MTX3 arm). This trial involved most European pediatric/lymphoma study groups and a Japanese group. Results Overall, 352 patients (96% ALK positive) were recruited between 1999 and 2005; 175 were randomly assigned to the MTX1 arm, and 177 were assigned to the MTX3 arm. Ninety-two percent of patients received protocol treatment. Median follow-up time is 3.7 years. Event-free survival (EFS) curves were superimposed with 2-year EFS rates (73.6% and 74.5% in the MTX1 and MTX3 arms, respectively; hazard ratio = 0.98; 91.76% CI, 0.69 to 1.38). Two-year overall survival rates were 90.1% and 94.9% in MTX1 and MTX3, respectively. Only two CNS relapses occurred (both in the MTX1 arm). Toxicity was assessed after 2,050 courses and included grade 4 hematologic toxicity after 79% and 64% of MTX1 and MTX3 courses, respectively (P < .0001); infection after 50% and 32% of courses, respectively (P < .0001); and grade 3 to 4 stomatitis after 21% and 6% of courses, respectively (P < .0001). CONCLUSION The results of the NHL-BFM90 study were reproduced in this large international trial. The methotrexate schedule of the NHL-BFM90 protocol including IT therapy can be safely replaced by a less toxic schedule of methotrexate 3 g/m(2) in a 3-hour infusion without IT therapy. |
| Brüggemann M, Schrauder A, Raff T, Pfeifer H, Dworzak M, Ottmann OG, Asnafi V, Baruchel A, Bassan R, Benoit Y, Biondi A, Cavé H, Dombret H, Fielding AK, Foà R, Gökbuget N, Goldstone AH, Goulden N, Henze G, Hoelzer D, Janka-Schaub GE, Macintyre EA, Pieters R, Rambaldi A, Ribera JM, Schmiegelow K, Spinelli O, Stary J, von Stackelberg A, Kneba M, Schrappe M, van Dongen JJ, European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL),International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) |
Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. [+] |
Leukemia 2010, 24: 521 |
|
| Assessment of minimal residual disease (MRD) has acquired a prominent position in European treatment protocols for patients with acute lymphoblastic leukemia (ALL), on the basis of its high prognostic value for predicting outcome and the possibilities for implementation of MRD diagnostics in treatment stratification. Therefore, there is an increasing need for standardization of methodologies and harmonization of terminology. For this purpose, a panel of representatives of all major European study groups on childhood and adult ALL and of international experts on PCR- and flow cytometry-based MRD assessment was built in the context of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. The panel summarized the current state of MRD diagnostics in ALL and developed recommendations on the minimal technical requirements that should be fulfilled before implementation of MRD diagnostics into clinical trials. Finally, a common terminology for a standard description of MRD response and monitoring was established defining the terms 'complete MRD response', 'MRD persistence' and 'MRD reappearance'. The proposed MRD terminology may allow a refined and standardized assessment of response to treatment in adult and childhood ALL, and provides a sound basis for the comparison of MRD results between different treatment protocols. |
| Brämswig J, Heiermann E, Heimes U, Hengst K, Schellong G |
Radiation induced thyroid dysfunction in pediatric Hodgkin's disease (HD). |
Med Pediat Oncol ; 15 |
|
| Brämswig J, Heimes U, Heiermann E, Schlegel W, Nieschlag E, Schellong G |
The effects of different cumulative doses of chemotherapy on testicular function. Results in 75 patients treated for Hodgkin's disease during childhood or adolescence. |
Cancer 1990, 65: 1298 |
|
| Brämswig J, Hörnig-Franz I, Riepenhausen M, Schellong G |
The challenge of pediatric Hodgkin's disease - Where is the balance between cure and long-term toxicity? |
Leukemia and Lymphoma 1990, 3: 183 |
|
| Brämswig J, Schellong G, Schlegel W, Hassel U, Heimes U |
Testicular function in boys after treatment for Hodgkin's Disease with or without procarbazine. |
Exp Clin Endocrinol 1993, 101, Suppl |
|
| Bucsky P, Parlowsky T |
Epidemiology and therapy of thyroid cancer in childhood and adolescence. |
Exp Clin Endocrinol Diabetes 1997, 105 Suppl 4: 70 |
|
| Buckley JD, Meadows AT, Kadin ME, Le Beau MM, Siegel S, Robison LL |
Pesticide exposures in children with non-Hodgkin lymphoma. |
Cancer 2000, 89: 2315 |
|
| Bürger B, Zimmermann M, Mann G, Kühl J, Loning L, Riehm H, Reiter A, Schrappe M |
Diagnostic cerebrospinal fluid examination in children with acute lymphoblastic leukemia. |
J Clin Oncol 2003, 21: 184 |
|
| von Bueren AO, von Hoff K, Benesch M, Rutkowski S |
Dose reductions of vincristine in children with medulloblastoma treated in the maintenance arm of the prospective multicenter trial HIT'91. |
Klinische Padiatrie 2009, 221: 396 |
|
| von Bueren AO, von Hoff K, Pietsch T, Gerber NU, Warmuth-Metz M, Deinlein F, Zwiener I, Faldum A, Fleischhack G, Benesch M, Krauss J, Kuehl J, Kortmann RD, Rutkowski S |
Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology. [+] |
Neuro-oncology 2011, 13: 669 |
|
| This study was designed to confirm the previously observed favorable survival rates and prognostic factors in young children with nonmetastatic medulloblastoma (MB) treated with postoperative chemotherapy alone. Patients who received a diagnosis during the period January 2001 through December 2005 and who were aged <4 years received 3 cycles of postoperative systemic multiagent chemotherapy and intraventricular methotrexate. In cases of complete remission, treatment was terminated after 2 additional cycles of chemotherapy. Otherwise, secondary surgery, radiotherapy, and consolidation chemotherapy were recommended. At a median follow-up of 4.5 years, the 5-year event-free survival (EFS) and overall survival (OS) rates (± standard error) for 45 patients (median age, 2.5 years) were 57% ± 8% and 80% ± 6%, respectively. Nineteen patients with desmoplastic/nodular MB variants had better 5-year EFS and OS rates (90% ± 7% and 100% ± 0%, respectively) than did 23 patients with classic MB (30% ± 11% and 68% ± 10%, respectively; P < .001 for EFS; P = .008 for OS). Five-year EFS and OS rates for 3 children with anaplastic MB were 33% ± 27%. Desmoplastic/nodular histology was an independent prognostic factor for EFS. Twenty-nine of 30 patients without postoperative residual tumor remained in continuous complete remission. Our results confirm that histology of MB variants is a strong prognostic factor in this age group. Sustained tumor control can be achieved by this chemotherapy regimen in young children with desmoplastic/nodular MB variants. For children with non-desmoplastic/nonnodular MB variants, for which predominantly local relapses lead to less favorable survival rates, local radiotherapy has been introduced after chemotherapy since 2006. |
| von Bueren AO, Warmuth-Metz M, Schlegel PG, Soerensen N, Krauss J, Roggendorf W, Pietsch T, Feiden W, Graf N, Pohl F, Flentje M, Kuehl J, Rutkowski S |
Late complete remission of supratentorial primitive neuroectodermal tumor (CNS-PNET) after multiple relapses. [+] |
Pediatr Blood Cancer 2011, 56: 503 |
|
| No abstract available |
| von Bueren AO, von Hoff K, Pietsch T, Gerber NU, Warmuth-Metz M, Deinlein F, Zwiener I, Faldum A, Fleischhack G, Benesch M, Krauss J, Kuehl J, Kortmann RD, Rutkowski S |
Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology. [+] |
Neuro Oncol 2011, 13: 669 |
|
| This study was designed to confirm the previously observed favorable survival rates and prognostic factors in young children with nonmetastatic medulloblastoma (MB) treated with postoperative chemotherapy alone. Patients who received a diagnosis during the period January 2001 through December 2005 and who were aged <4 years received 3 cycles of postoperative systemic multiagent chemotherapy and intraventricular methotrexate. In cases of complete remission, treatment was terminated after 2 additional cycles of chemotherapy. Otherwise, secondary surgery, radiotherapy, and consolidation chemotherapy were recommended. At a median follow-up of 4.5 years, the 5-year event-free survival (EFS) and overall survival (OS) rates (± standard error) for 45 patients (median age, 2.5 years) were 57% ± 8% and 80% ± 6%, respectively. Nineteen patients with desmoplastic/nodular MB variants had better 5-year EFS and OS rates (90% ± 7% and 100% ± 0%, respectively) than did 23 patients with classic MB (30% ± 11% and 68% ± 10%, respectively; P < .001 for EFS; P = .008 for OS). Five-year EFS and OS rates for 3 children with anaplastic MB were 33% ± 27%. Desmoplastic/nodular histology was an independent prognostic factor for EFS. Twenty-nine of 30 patients without postoperative residual tumor remained in continuous complete remission. Our results confirm that histology of MB variants is a strong prognostic factor in this age group. Sustained tumor control can be achieved by this chemotherapy regimen in young children with desmoplastic/nodular MB variants. For children with non-desmoplastic/nonnodular MB variants, for which predominantly local relapses lead to less favorable survival rates, local radiotherapy has been introduced after chemotherapy since 2006. |
| von Bueren AO, Bacolod MD, Hagel C, Heinimann K, Fedier A, Kordes U, Pietsch T, Koster J, Grotzer MA, Friedman HS, Marra G, Kool M, Rutkowski S |
Mismatch repair deficiency: a temozolomide resistance factor in medulloblastoma cell lines that is uncommon in primary medulloblastoma tumours. [+] |
British journal of cancer 2012, 107: 1399-408 |
|
| Tumours are responsive to temozolomide (TMZ) if they are deficient in O(6)-methylguanine-DNA methyltransferase (MGMT), and mismatch repair (MMR) proficient. |
| Buffler PA, Kwan ML, Reynolds P, Urayama KY |
Environmental and genetic risk factors for childhood leukemia: appraising the evidence. |
Cancer Invest 2005, 23: 60 |
|
| Bührer C, Hartmann R, Fengler R, Dopfer R, Gadner H, Gerein V, Göbel U, Reiter A, Ritter J, Henze G |
Superior prognosis in combined compared to isolated bone marrow relapses in salvage therapy of childhood acute lymphoblastic leukemia. |
Med Pediatr Oncol 1993, 21: 470 |
|
| Buchanan GR, Adix L |
Grading of hemorrhage in children with idiopathic thrombocytopenic purpura. [+] |
The Journal of pediatrics 2002, 141: 683 |
|
| To develop an instrument to allow semiquantitative assessment of hemorrhage in children with idiopathic thrombocytopenic purpura (ITP). |
| Bunin GR |
Nongenetic causes of childhood cancers: evidence from international variation, time trends, and risk factor studies. |
Toxicol Appl Pharmacol 2004, 199: 91 |
|
| Buchanan GR, Adix L |
Current challenges in the management of children with idiopathic thrombocytopenic purpura. [+] |
Pediatric blood & cancer 2006, 47(5 Suppl): 681 |
|
| Much progress has been made during the past several decades in the diagnosis and management of childhood idiopathic thrombocytopenic purpura (ITP). Although we do not yet know ITP's cause, opportunities for research discovery in other areas have blossomed in recent years. One major step forward has been realization that outcomes other than platelet count are important in children with ITP, most especially the severity of hemorrhage, cost and side effects of treatment, and overall quality of life. The classical definition of chronic ITP (thrombocytopenia lasting greater than 6 months) has been questioned. Debate continues whether ITP can truly be cured, especially when it lasts for years. Much excitement has recently been generated as a result of a new mechanism of ITP treatment, that is, enhancing platelet production. Yet problems continue regarding how best to conduct research involving newly diagnosed ITP patients, for a number of barriers are still to be overcome. Fortunately, however, abundant information and support for ITP patients and their families is now much more available than in years past. |
| Burdach S, Jürgens H, Peters C, Nürnberger W, Mauz-Körholz C, Körholz D, Paulussen M, Pape H, Dilloo D, Koscielniak E, et al. |
Myeloablative radiochemotherapy and hematopoietic stem-cell rescue in poor-prognosis Ewing's sarcoma. |
J Clin Oncol 1993, 11: 1482 |
|
| Burdach S, Müschenich M, Josephs W, Frisch J, Schulz G, Jürgens H, Göbel U |
Granulocyte-macrophage-colony stimulating factor for prevention of neutropenia and infections in children and adolescents with solid tumors. Results of a prospective randomized study. |
Cancer 1995, 76: 510 |
|
| Burdach S, Nürnberger W, Laws H, Engel B, Dirksen U, Krauth K, Pape H, Kahn T, Körholz D, Gadner H, Göbel U, Jürgens H |
Myeloablative therapy, stem cell rescue and gene transfer in advanced Ewing tumors. |
Bone Marrow Transplant 1996, 18 Suppl 1:S67 |
|
| Burdach S, van Kaick B, Laws H, Ahrens S, Haase R, Körholz D, Pape H, Dunst J, Kahn T, Willers R, Engel B, Dirksen U, Kramm C, Nurnberger W, Heyll A, Ladenstein R, Gadner H, Jürgens H, Go el |
Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors. An update after long-term follow-up from two centers of the European Intergroup study EICESS. Stem-Cell Transplant Programs at Dusseldorf University Medical Center, Germany and St. Anna Kinderspital, Vienna, Austria. |
Ann Oncol 2000, 11: 1451 |
|
| Burdach S, Jürgens H |
High-dose chemoradiotherapy (HDC) in the Ewing family of tumors (EFT). |
Crit Rev Oncol Hematol 2002, 41: 169 |
|
| Burkhardt-Hammer T, Spix C, Brenner H, Kaatsch P, Berthold F, Hero B, Michaelis J |
Long-term survival of children with neuroblastoma prior to the neuroblastoma screening project in Germany. |
Med Pediatr Oncol 2002, 39: 156 |
|
| Burdach S, Meyer-Bahlburg A, Laws H, Haase R, van Kaik B, Metzner B, Wawer A, Finke R, Göbel U, Haerting J, Pape H, Gadner H, Dunst J, Jürgens H |
High-dose therapy for patients with primary multifocal and early relapsed Ewing's tumors. |
J Clin Oncol 2003, 21: 3072 |
|
| Burger B, Beier R, Zimmermann M, Beck JD, Reiter A, Schrappe M |
Osteonecrosis: a treatment related toxicity in childhood acute lymphoblastic leukemia (ALL)--experiences from trial ALL-BFM 95. [+] |
Pediatric blood & cancer 2005, 44: 220 |
|
| BACKGROUND: Osteonecrosis (ON) as a complication during treatment of acute lymphoblastic leukemia (ALL) has gained rising attention over the past decade. Corticosteroids, representing an essential element of antileukemic therapy, are known to induce ON, which in turn may cause significant morbidity. Due to spontaneous reporting of affected patients with ON, a group-wide evaluation was performed to determine incidence, risk factors, and morbidity for ON. PROCEDURE: Patients were identified via spontaneous reporting to the study center and via questionnaire, addressing all 64 participating centers. We retrospectively analyzed 1,951 patients below 18 years of age who were treated according to trial ALL-BFM 95 between 01.01.1996 and 30.06.2000. RESULTS: Thirty-one patients (14 male, 17 female) affected by ON were identified. The overall 5-year cumulative incidence for ON is 1.8%. The incidence for patients <10 years is 0.2%, whereas for patients >/=10 years it is 8.9% (P = 0.00) and 16.7% (P = 0.003) for patients >/=15 years. The majority (n = 20) showed ON in two or more joints, and the joints most commonly affected were knees (14 patients, 24 affected knees) and hips (11 patients, 20 affected joints). Thirteen out of 31 patients had to undergo surgery in the course of their disease. CONCLUSIONS: Symptomatic ON is a rare event in patients treated with BFM-type chemotherapy with an overall 5-year cumulative incidence of 1.8%. The age group >/=10 years, and particularly adolescents >/=15 years have a significantly higher risk of developing ON. |
| Burkhardt B, Zimmermann M, Oschlies I, Niggli F, Mann G, Parwaresch R, Riehm H, Schrappe M, Reiter A, BFM Group |
The impact of age and gender on biology, clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescence. |
Br J Haematol 2005, 131: 39 |
|
| Burkhardt B, Woessmann W, Zimmermann M, Kontny U, Vormoor J, Doerffel W, Mann G, Henze G, Niggli F, Ludwig WD, Janssen D, Riehm H, Schrappe M, Reiter A |
Impact of cranial radiotherapy on central nervous system prophylaxis in children and adolescents with central nervous system-negative stage III or IV lymphoblastic lymphoma. |
J Clin Oncol 2006, 24: 491 |
|
| Burkhardt B, Moericke A, Klapper W, Greene F, Salzburg J, Damm-Welk C, Zimmermann M, Strauch K, Ludwig WD, Schrappe M, Reiter A |
Pediatric precursor T lymphoblastic leukemia and lymphoblastic lymphoma: Differences in the common regions with loss of heterozygosity at chromosome 6q and their prognostic impact. [+] |
Leukemia & lymphoma 2008, 49: 451 |
|
| Deletions on chromosome 6q are frequently reported in hematological malignancies. However, their biological or prognostic impact has not yet been clarified. This study analyzed loss of heterozygosity (LOH) at chromosome 6q and compared the LOH findings in pediatric precursor T lymphoblastic lymphoma (T-LBL) with the LOH findings in precursor-T lymphoblastic leukemia (T-ALL). For LOH analyses, a set of 25 microsatellite-markers on 6q14-q24 were examined. All patients were treated uniformly according to ALL-BFM-type treatment-strategy. A total of 1671 markers were successfully analyzed from 108 T-LBL patients. LOH was detected in 21 T-LBL patients. There was clear association between LOH at 6q and an increased risk of relapse. In comparison, 3109 markers were successfully analyzed from 127 T-ALL-patients. LOH was detected in 16 patients, but was not associated with increased relapse-rate. The localization of the common LOH regions identified for T-LBL and T-ALL samples did not overlap. Therefore patterns of LOH at 6q and the prognostic impact of LOH differ between T-ALL and T-LBL. These results hint at biologic differences between the two diseases. |
| Burkhardt B, Reiter A, Landmann E, Lang P, Lassay L, Dickerhoff R, Lakomek M, Henze G, von Stackelberg A |
Poor outcome for children and adolescents with progressive disease or relapse of lymphoblastic lymphoma: a report from the berlin-frankfurt-muenster group. [+] |
Journal of clinical oncology 2009, 27: 3363 |
|
| PURPOSE: Little is known about the outcome of pediatric patients with lymphoblastic lymphoma (LBL) who suffer from progressive disease or relapse. PATIENTS AND METHODS: We analyzed the pattern of LBL relapses after current non-Hodgkin's lymphoma Berlin-Frankfurt-Muenster (BFM) frontline therapy between April 1990 and March 2003. Relapse therapy was according to acute lymphoblastic leukemia (ALL) -Relapse-BFM protocols or ALL-BFM protocols for high-risk patients. RESULTS: Twenty-eight (11%) of 251 registered patients with precursor T-cell LBL (T-LBL) and six (8%) of 73 patients with precursor B-cell LBL (pB-LBL) suffered from relapse. Of the 28 patients with T-LBL, one died from infection during relapse chemotherapy, 18 failed to achieve stable remission and died from disease progression, and nine reached allogeneic stem-cell transplantation (SCT). Two of these nine patients who underwent SCT died from transplantation-associated toxicity, three died from disease progression, and four are still alive. These four patients are in second remission of their lymphoma for 48, 68, 125, and 131 months, respectively, after allogeneic SCT. One of the four patients developed colon adenocarcinoma 47 months after SCT. Of the six patients with pB-LBL who experienced relapse, one patient died as a result of toxicity of relapse chemotherapy, two died from disease progression after chemotherapy, and three received allogeneic SCT. Of these, two died from subsequent disease progression, and one is still alive 57 months after allogeneic SCT. CONCLUSION: Using modern conventional therapy in the frontline treatment of LBL, 10% of patients suffer from progressive disease or relapse. Because of the extremely poor reinduction success, the salvage rate for these patients is poor, with only a 14% (SE = 6%) overall survival. Long-term survival was only achieved in those few patients who were able to undergo an allogeneic SCT. |
| Burdach S, Thiel U, Schöniger M, Haase R, Wawer A, Nathrath M, Kabisch H, Urban C, Laws HJ, Dirksen U, Steinborn M, Dunst J, Jürgens H, Meta-EICESS Study Group |
Total body MRI-governed involved compartment irradiation combined with high-dose chemotherapy and stem cell rescue improves long-term survival in Ewing tumor patients with multiple primary bone metastases. [+] |
Bone marrow transplantation 2010, 45: 483 |
|
| We examined the role of total body magnetic resonance imaging (TB-MRI)-governed involved compartment irradiation (ICI) and high-dose chemotherapy (HDC), followed by stem cell rescue (SCR) in patients with high-risk Ewing tumors (ETs) with multiple primary bone metastases (high-risk ET-MBM). Eleven patients with high-risk ET-MBM receiving initial assessment of involved bones by TB-MRI were registered from 1995 to 2000 (group A). In all, 6 patients out of 11 had additional lung disease at initial diagnosis; all had multifocal bone disease with more than three bones involved. After systemic induction with etoposide, vincristine, adriamycin (doxorubicin), ifosfamide, and actinomycin D (EVAIA) or VAIA chemotherapy, ICI of all sites positive by TB-MRI was administered, followed by HDC and SCR. A second group matched for observation period and consisting of 26 patients with more than three involved bones at diagnosis was treated with the European Intergroup Cooperative Ewing Sarcoma Study-92 (EICESS-92) protocol (group B). These patients did not receive TB-MRI and consequently did not receive TB-MRI-governed ICI, or HDC and SCR. Survival in group A vs group B was 45 vs 8% at 5 years and 27 vs 8% at 10 years after diagnosis (log rank and Breslow: P<0.005). We conclude that TB-MRI-governed ICI followed by HDC and SCR in ET-MBM is feasible and warrants further evaluation in prospective studies. |
| Burkhardt B, Oschlies I, Klapper W, Zimmermann M, Woessmann W, Meinhardt A, Landmann E, Attarbaschi A, Niggli F, Schrappe M, Reiter A |
Non-Hodgkin's lymphoma in adolescents: experiences in 378 adolescent NHL patients treated according to pediatric NHL-BFM protocols. [+] |
Leukemia 2011, 25: 153 |
|
| Age-related differences in the distribution, biology and treatment response of non-Hodgkin's lymphoma (NHL) in adolescents remain to be elucidated. The current analyses present clinical parameters and outcomes of adolescents treated in pediatric NHL-BFM trials. Patients were stratified by histological subtype: lymphoblastic lymphoma (LBL); mature B-NHL, including Burkitt's lymphoma/leukemia (BL/B-AL), diffuse B-cell lymphoma (DLBCL-CB) and mediastinal B-cell lymphoma (PMLBL); and anaplastic large cell lymphoma (ALCL). Between October 1986 and December 2007, 2915 patients were registered, including 378 (13%) adolescents (15-18 years) with BL/B-AL (n=101), ALCL (n=74), DLBCL-CB (n=55), T-LBL (n=45), PMLBL (n=24), pB-LBL (n=13) and rare or not-specified NHL subtypes (n=66). The 5-year event-free survival (EFS) was 79±2% for adolescents compared with 85±1% for patients aged <15 years (P=0.014). EFS was 83±7% for adolescents with T-LBL, 82±4% with BL/B-AL, 85±5% with DLBCL-CB, 57±10% with PMLBL and 70±6% with ALCL. According to sex, the 5-year EFS in females versus males, respectively, was 70±5 versus 83±2% overall (P=0.004), 57±17 versus 92±6% (P=0.0036) for T-LBL patients and 71±9 versus 97±3% (P=0.0067) for DLBCL-CB patients. Adolescents with NHL treated according to pediatric NHL-BFM protocols had an EFS of 79±2%, which is marginally inferior to that of children. In adolescents with T-LBL and DLBCL-CB, female sex was associated with a worse prognosis. |
| Busch K, Borkhardt A, Wossmann W, Reiter A, Harbott J |
Combined polymerase chain reaction methods to detect c-myc/IgH rearrangement in childhood Burkitt's lymphoma for minimal residual disease analysis. |
haematologica 2004, 89: 818 |
|
| Butturini A, Gale RP, Verlander PC, Adler-Brecher B, Gillio AP, Auerbach AD |
Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study. [+] |
Blood 1994, 84: 1650 |
|
| We analyzed data from 388 subjects with Fanconi anemia reported to the International Fanconi Anemia Registry (IFAR). Of those, 332 developed hematologic abnormalities at a median age of 7 years (range, birth to 31 years). Actuarial risk of developing hematopoietic abnormalities was 98% (95% confidence interval, 93% to 99%) by 40 years of age. Common hematologic abnormalities were thrombocytopenia and pancytopenia. These were often associated with decreased bone marrow (BM) cellularity (75% of cases studied). Clonal cytogenetic abnormalities developed in 23 of 68 persons with BM failure who had adequate studies. Actuarial risk of clonal cytogenetic abnormalities during BM failure was 67% (47% to 87%) by 30 years of age. Fifty-nine subjects developed myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Actuarial risk of MDS or AML was 52% (37% to 67%) by 40 years of age. Risk was higher in persons with than in those without a prior clonal cytogenetic abnormality (3% [0% to 9%] v 35% [0% to 79%]; P = .006). One hundred twenty persons died of hematologic causes including BM failure, MDS or AML and treatment related complications. Actuarial risk of death from hematologic causes was 81% (67% to 90%) by 40 years of age. |
| Bührer C, Hartmann R, Fengler R, Döpfer R, Gadner H, Gerein V, Göbel U, Reiter A, Ritter J, Henze G |
Superior prognosis in combined compared to isolated bone marrow relapses in salvage therapy of childhood acute lymphoblastic leukemia. |
Med Pediatr Oncol 1993, 21: 470 |
|
| Bührer C, Hartmann R, Fengler R, Schober S, Arlt I, Loewke M, Henze G |
Importance of effective central nervous system therapy in isolated bone marrow relapse of childhood acute lymphoblastic leukemia. BFM (Berlin-Frankfurt-Münster) Relapse Study Group. |
Blood 1994, 83: 3468 |
|
| Bührer C, Hartmann R, Fengler R, Rath B, Schrappe M, Janka-Schaub G, Henze G |
Peripheral blast counts at diagnosis of late isolated bone marrow relapse of childhood acute lymphoblastic leukemia predict response to salvage chemotherapy and outcome. Berlin-Frankfurt-Münster Relapse Study Group. |
J Clin Oncol 1996, 14: 2812 |
|
| Bürger D, von Schweinitz D, Weinel P, Mildenberger H |
HB89. |
Chirurg 1992, 63: 193 |
|
| 232 items found |
