| Autor(en) |
Titel |
Quelle |
Links |
| Rachmilewitz EA, Giardina PJ |
How I treat thalassemia. [+] |
Blood 2011, 118: 3479 |
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| The purpose of this article is to set forth our approach to diagnosing and managing the thalassemias, including β-thalassemia intermedia and β-thalassemia major. The article begins by briefly describing recent advances in our understanding of the pathophysiology of thalassemia. In the discussion on diagnosing the condition, we cover the development of improved diagnostic tools, including the use of very small fetal DNA samples to detect single point mutations with great reliability for prenatal diagnosis of homozygous thalassemia. In our description of treatment strategies, we focus on how we deal with clinical manifestations and long-term complications using the most effective current treatment methods for β-thalassemia. The discussion of disease management focuses on our use of transfusion therapy and the newly developed oral iron chelators, deferiprone and deferasirox. We also deal with splenectomy and how we manage endocrinopathies and cardiac complications. In addition, we describe our use of hematopoietic stem cell transplantation, which has produced cure rates as high as 97%, and the use of cord blood transplantation. Finally, we briefly touch on therapies that might be effective in the near future, including new fetal hemoglobin inducers and gene therapy. |
| Raimondi SC, Chang MN, Ravindranath Y |
Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821. |
Blood 1999, 94: 3707 |
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| Rajantie J, Zeller B, Treutiger I, Rosthöj S, NOPHO ITP working group and five national study groups |
Vaccination associated thrombocytopenic purpura in children. [+] |
Vaccine 2007, 25: 1838 |
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| Patients who presented with purpura and blood platelets <30x10(9)/l within 1 month after vaccination were collected from a population based material of 506 consecutive pediatric patients with newly diagnosed ITP. Of the 35 such patients, 24 had thrombocytopenia after MMR vaccination giving an estimated ITP risk of approximately 1 in 30,000 MMR inoculations. Symptoms of the 35 patients were nearly always acute. Thrombocytopenia disappeared within a month in 74% of the study patients and lasted longer than 6 months in only 10%. Bleeding episodes were uncommon during the follow-up period. We conclude that the incidence of symptomatic thrombocytopenia after vaccinations is much lower than that after respective natural infections and that the outcome in most cases is excellent. |
| Ramakers-van Woerden N, Pieters R, Loonen A, Hubeek I, van Drunen E, Beverloo H, Slater R, Harbott J, Seyfarth J, van Wering E, Hahlen K, Schmiegelow K, Janka-Schaub G, Veerman A |
TEL/AML1 gene fusion is related to in vitro drug sensitivity for L-asparaginase in childhood acute lymphoblastic leukemia. |
Blood 2000, 96: 1094 |
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| Ramakers-van Woerden N, Pieters R, Slater R, Loonen A, Beverloo H, van Drunen E, Heyman M, Moreno T, Rots M, van Wering E, Kamps W, Janka-Schaub G, Veerman A |
In vitro drug resistance and prognostic impact of p16INK4A/P15INK4B deletions in childhood T-cell acute lymphoblastic leukaemia. |
Br J Haematol 2001, 112: 680 |
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| Ramakers-van Woerden N, Pieters R, Hoelzer D, Slater R, Den Boer M, Loonen A, Harbott J, Janka-Schaub G, Ludwig W, Ossenkoppele G, van Wering E, Veerman A |
In vitro drug resistance profile of Philadelphia positive acute lymphoblastic leukemia is heterogeneous and related to age. |
Med Pediatr Oncol 2002, 38: 379 |
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| Ramakers-van Woerden NL, Beverloo HB, Veerman AJ, Camitta BM, Loonen AH, van Wering ER, Slater RM, Harbott J, den Boer ML, Ludwig WD, Haas OA, Janka-Schaub GE, Pieters R |
In vitro drug-resistance profile in infant acute lymphoblastic leukemia in relation to age, MLL rearrangements and immunophenotype. [+] |
Leukemia 2004, 18: 521 |
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| Acute lymphoblastic leukemia (ALL) in infants under 1 year is strongly associated with translocations involving 11q23 (MLL gene), CD10-negative B-lineage (proB) immunophenotype, and poor outcome. The present study analyses the relationship between age, MLL rearrangements, proB-lineage, and in vitro drug resistance determined using the MTT assay. Compared to 425 children aged over 1 year with common/preB (c/preB) ALL, the 44 infants were highly resistant to steroids (for prednisolone (PRED) more than 580-fold, P=0.001) and L-asparaginase (L-ASP) (12-fold, P=0.001), but more sensitive to cytarabine (AraC) (1.9-fold, P=0.001) and 2-chlorodeoxyadenosine (2-CdA) (1.7-fold, P<0.001). No differences were found for vincristine, anthracyclines, thiopurines, epipodophyllotoxines, or 4-hydroperoxy (HOO)-ifosfamide. ProB ALL of all ages had a profile similar to infant ALL when compared with the group of c/preB ALL: relatively more resistant to L-ASP and PRED (and in addition thiopurines), and more sensitive to AraC and 2-CdA. Age was not related to cellular drug resistance within the proB ALL group (<1 year, n=32, vs >/=1 year, n=19), nor within the MLL-rearranged ALL (<1 year, n=34, vs >/=1 year, n=8). The translocation t(4;11)(q21;q23)-positive ALL cases were more resistant to PRED (>7.4-fold, P=0.033) and 4-HOO-ifosfamide (4.4-fold, P=0.006) than those with other 11q23 abnormalities. The expression of P-glycoprotein, multidrug-resistance protein, and lung-resistance protein (LRP) was not higher in infants compared to older c/preB ALL patients, but LRP was higher in proB ALL and MLL-rearranged ALL of all ages. In conclusion, infants with ALL appear to have a distinct in vitro resistance profile with the proB immunophenotype being of importance. The role of MLL cannot be excluded, with the t(4;11) being of special significance, while age appears to play a smaller role. |
| Raney B, Parham D, Sommelet-Olive D, Stevens M, Treuner J, Carli M |
Summary of the International Symposium on Childhood Non-Rhabdomyosarcoma Soft-Tissue Sarcomas, Padua, Italy, February 10-12, 1994. |
Med Pediatr Oncol 1996, 26: 425 |
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| Ratei R, Sperling C, Karawajew L, Schott G, Schrappe M, Harbott J, Riehm H, Ludwig W |
Immunophenotype and clinical characteristics of CD45-negative and CD45-positive childhood acute lymphoblastic leukemia. |
Annals Hematology 1998, 77: 107 |
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| Ratei R, Basso G, Dworzak M, Gaipa G, Veltroni M, Rhein P, Biondi A, Schrappe M, Ludwig WD, Karawajew L, AIEOP-BFM-FCM-MRD-Study Group |
Monitoring treatment response of childhood precursor B-cell acute lymphoblastic leukemia in the AIEOP-BFM-ALL 2000 protocol with multiparameter flow cytometry: predictive impact of early blast reduction on the remission status after induction. [+] |
Leukemia 2009, 23: 528 |
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| Treatment response is a strong outcome predictor for childhood acute lymphoblastic leukemia (ALL). Here, we evaluated the predictive impact of flow cytometric blast quantification assays (absolute blast count, BC, and blast reduction rate, BRR) in peripheral blood (pB) and/or bone marrow (BM) at early time points of induction therapy (days 0, 8 and 15) on the remission status in the AIEOP-BFM-ALL 2000 protocol. At the single parameter level (905 patients), the strongest predictive parameter for the remission status as a dichotomous minimal residual disease (MRD) parameter (positive/negative) has been provided by the BC at day 15 in BM (cutoff: 17 blasts/microl; 50 vs 15%; odds ratio: 5.6; 95% confidence interval: 4.1-7.6, P<0.001), followed by the BRR at day 15 in BM and by the BC at day 8 in pB (odds ratios: 3.8 and 2.6, respectively). In the multiple regression analysis (440 patients), BC in pB (d0 and d8) and in BM (d15) as well as BRR at day 8 in pB provided significantly contributing variables with an overall correct prediction rate of 74.8%. These data show that the quantitative assessment of early response parameters, especially absolute BCs at day 15 in BM, has a predictive impact on the remission status after induction therapy. |
| Ravindranath Y, Abella E, Krischer JP, Wiley J, Inoue S, Harris M, Chauvenet A, Alvarado CS, Dubowy R, Ritchey AK et al. |
Acute myeloid leukemia (AML) in Down's syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498. |
Blood 1992, 80: 2210 |
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| Redlich A, Boxberger N, Strugala D, Frühwald MC, Leuschner I, Kropf S, Bucsky P, Vorwerk P |
Systemic Treatment of Adrenocortical Carcinoma in Children: Data from the German GPOH-MET 97 Trial. [+] |
Klinische Padiatrie 2012, 224: 366 |
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| Adrenocortical cancer (ACC) in childhood is a rare disease with poor prognosis. Complete surgical resection, systemic chemotherapy, and mitotane therapy are important curative treatment options for patients with advanced-stage tumors. Since 1997, pediatric ACC patients in Germany have been treated according to the non-randomized, single arm study GPOH-MET-97.Data regarding disease course, treatment, and survival rates of 60 patients (age 0.24-17.8 years) with ACC treated according to the GPOH-MET-97 protocol were collected and analyzed to determine outcome, with a focus on examining the effectiveness of mitotane therapy.Among all patients, event-free survival and overall survival were found to be 43.3% and 64.8%, respectively. Chemotherapy with VCR, IFO, ADR, CARBO, and VP16 had been provided to 34 patients (56.6%) in different settings (neoadjuvant, adjuvant, and salvage) and mitotane therapy to 32 patients (53.3%). Duration of mitotane treatment longer than 6 months and mitotane levels greater than 14 mg/l were found to be associated with significantly better survival. Local relapse was found to be associated with a worse prognosis compared to distant metastasis only.Systemic chemotherapy and mitotane therapy are important therapeutic options in the treatment of advanced pediatric ACC patients. Neoadjuvant therapy should be considered for patients with primarily incomplete resectable or inoperable tumors, and tumor spillage is an indication for adjuvant chemo- and mitotane therapy. All pediatric ACC patients should be treated in pediatric oncological centers according to a consistent protocol in a highly interdisciplinary setting. |
| Redlich A, Boxberger N, Kurt Werner S, Frühwald M, Rohrer T, Vorwerk P |
Sensitivity of fine-needle biopsy in detecting pediatric differentiated thyroid carcinoma. [+] |
Pediatric blood & cancer 2012, 59: 233 |
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| Differentiated thyroid carcinomas (DTC) are uncommon in children. Since the frequency of malignancy is assumed to be high in pediatric symptomatic thyroid nodules, carcinomas should be ruled out reliably. The objective of this study was to assess the sensitivity of fine-needle biopsy (FNB) in diagnosing children with DTC. |
| Rees DC, Williams TN, Gladwin MT |
Sickle-cell disease. [+] |
Lancet 2010, 376: 2018-31. |
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| Sickle-cell disease is one of the most common severe monogenic disorders in the world. Haemoglobin polymerisation, leading to erythrocyte rigidity and vaso-occlusion, is central to the pathophysiology of this disease, although the importance of chronic anaemia, haemolysis, and vasculopathy has been established. Clinical management is basic and few treatments have a robust evidence base. One of the main problems of sickle-cell disease in children is the development of cerebrovascular disease and cognitive impairment, and the role of blood transfusion and hydroxycarbamide for prevention of these complications is starting to be understood. Recurrent episodes of vaso-occlusion and inflammation result in progressive damage to most organs, including the brain, kidneys, lungs, bones, and cardiovascular system, which becomes apparent with increasing age. Most people with sickle-cell disease live in Africa, where little is known about this disease; however, we do know that the disorder follows a more severe clinical course in Africa than for the rest of the world and that infectious diseases have a role in causing this increased severity of sickle-cell disease. More work is needed to develop effective treatments that specifically target pathophysiological changes and clinical complications of sickle-cell disease. |
| Rehan N, Bieling P, Winkler P, Helmke K, Maas R, Baldini N, Heise U, Fuchs N, Winkler K |
The prognostic significance of tumor volume in osteosarcoma with neoadjuvant chemotherapy. |
Klin Pädiatr 1993, 205: 200 |
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| Reiter A, Schrappe M, Ludwig W, Lampert F, Harbott J, Henze G, Niemeyer C, Gadner H, Muller-Weihrich S, Ritter J, |
Favorable outcome of B-cell acute lymphoblastic leukemia in childhood. |
Blood 1992, 80: 2471 |
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| Reiter A |
Therapy of B-cell acute lymphoblastic leukaemia in childhood. |
Baillieres Clin Haematol 1994, 7: 321 |
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| Reiter A, Schrappe M, Ludwig W, Hiddemann W, Sauter S, Henze G, Zimmermann M, Lampert F, Havers W, Niethammer D, |
Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86. |
Blood 1994, 84: 3122 |
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| Reiter A, Schrappe M, Tiemann M, Parwaresch R, Zimmermann M, Yakisan E, Dopfer R, Bucsky P, Mann G, Gadner H |
Successful treatment strategy for Ki-1 anaplastic large-cell lymphoma of childhood. |
J Clin Oncol 1994, 12: 899 |
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| Reiter A, Schrappe M, Yakisan E, Sauter S, Ebell W, Zimmermann M, Hartmann W, Kremens B, Kuhn N, Claviez A, Sauerbrey A, Riehm H |
NHL-BFM 90 therapy study in treatment of malignant non-Hodgkin's lymphoma in children and adolescents. Part 3 |
Klin Pädiatr 1994, 206: 242 |
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| Reiter A, Schrappe M, Yakisan E, Sauter S, Henzler D, Zimmermann M, Graf N, Fengler R, Kühl J, Fleischhack G, Dörffel W, Kluba U, Riehm H |
NHL-BFM 90 therapy study in treatment of malignant non-Hodgkin's lymphomas in children and adolescents. Part 2 |
Klin Pädiatr 1994, 206: 234 |
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| Reiter A, Tiemann M, Ludwig W, Wacker H, Yakisan E, Schrappe M, Henzler D, Sykora K, Brandt A, Odenwald E, Riehm H, Parwaresch R |
NHL-BFM 90 therapy study in treatment of malignant non-Hodgkin's lymphomas in children and adolescents. Part 1 |
Klin Pädiatr 1994, 206: 222 |
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| Reiter A, Zimmermann W, Zimmermann M, Schweinitz D, Riehm H, Mildenberger H |
The role of initial laparotomy and second-look surgery in the treatment of abdominal B-cell non-Hodgkin's lymphoma of childhood. A report of the BFM Group. |
Eur J Pediatr Surg 1994, 4: 74 |
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| Reiter A, Schrappe M, Parwaresch R, Henze G, Müller-Weihrich S, Sauter S, Sykora K, Ludwig W, Gadner H, Riehm H |
Non-Hodgkin's lymphomas of childhood and adolescence. |
J Clin Oncol 1995, 13: 359 |
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| Zur, Reiter A, Tomeczkowski J, Sykora K |
A non-radioactive method for detection of monoclonal cell populations in patients with Burkitt's Lymphoma. |
Molecular Biology of Hematopoiesis 1996, 159 |
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| Reiter A |
Non-Hodgkin-Lymphome. |
Diagnostische und therapeutische Standards 1997, 89 |
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| Reiter A, Riehm H |
Large-cell lymphomas in children. |
The Non-Hodgkin-Lymphomas 1997, 829 |
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| Reiter A, Seidemann K, Schrappe M |
Therapie der Non-Hodgkin-Lymphome im Kindesalter. |
Klin Onkologie 1997, 16 |
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| Zur, Reiter A, Welte K, Sykora K |
Detection of translocation t(8;14)(q24;132) in pediatric Burkitt's lymphomas using "long distance" polymerase chain reaction. |
Klin Pädiatr 1997, 209: 165 |
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| Reinhardt D, Pekrun A, Lakomek M, Ritter J, Creutzig U |
Isolierte Myelosarkome der Haut im Kindesalter. |
Monatsschrift Kinderheilkunde 1999, 147: 346 |
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| Reinhardt D, Pekrun A, Lakomek M, Ritter J, Creutzig U |
Primary isolated myeolosarcoma in childhood. |
Klin Pädiatr 1999, 211: 245 |
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| Reiter A, Schrappe M, Tiemann M, Ludwig W, Yakisan E, Zimmermann M, Mann G, Chott A, Ebell W, Klingebiel T, Graf N, Kremens B, Müller-Weihrich S, Pluss H, Zintl F, Henze G, Riehm H |
Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy. |
Blood 1999, 94: 3294 |
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| Reinhardt D, Pekrun A, Lakomek M, Zimmermann M, Ritter J, Creutzig U |
Primary myelosarcomas are associated with a high rate of relapse. |
Br J Haematol 2000, 110: 863 |
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| Reiter A, Schrappe M, Ludwig W, Tiemann M, Parwaresch R, Zimmermann M, Schirg E, Henze G, Schellong G, Gadner H, Riehm H |
Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma. |
Blood 2000, 95: 416 |
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| Reinhardt D, Lanvers C, Ritter J, and Creutzig U |
Acute promyelocytic leukemia in children – results of the AML-BFM 93/98 studie. |
Oncol 2001, 24 |
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| Reinhardt D, Creutzig U |
Isolated myelosarcoma in children--update and review. |
Leuk Lymphoma 2002, 43: 565 |
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| Reinhardt D, Hempel G, Fleischhack G, Schulz A, Boos J, Creutzig U |
Liposomal daunorubicine combined with cytarabine in the treatment of relapsed/refractory acute myeloid leukemia in children. |
Klin Pädiatr 2002, 214: 188 |
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| Reinhardt D, Hempel G, Fleischhack G, Schulz A, Boos J, Creutzig U |
Effektive Rezidivtherapie der akuten myeloischen Leukämie im Kindesalter mit liposomalem Daunorubicin und Cytarabin. |
Klinische Pädiatrie 2002, 214: 188 |
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| Reinhardt D, Langebrake C, Creutzig U, Vormoor J, Brune C, Thorwesten M, Ingiliz P, Hrusak O, Dworzak M, Griesinger F |
Minimal residual disease in acute myeloid leukemia in children - standardization and evaluation of immunophenotyping in the AML-BFM-98 study. |
Klinische Pädiatrie 2002, 214: 179 |
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| Reinhardt D, Puhlmann U, Vorwerk H, Creutzig U, Ziemann Ch |
Impact of Cyclooxygenase-2 Inhibitors on P-Glycoprotein-Mediated Multidrug Resistance in Acute Myeloid Leukemias in Childhood. |
Blood 2002, 100: 321a-321a |
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| Reinhardt D, Thiele C, Creutzig U |
Neuropsychological sequelae in children with AML treated with or without prophylactic CNS-irradiation. |
Klin Pädiatr 2002, 214: 22 |
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| Reinhardt D, Zimmermann M, Ritter J, Bender-Götze Ch, Creutzig U |
Comparison of Allogeneic Matched Related Stem Cell Transplantation in 1st CR with Chemotherapy alone in Children with High-Risk AML. |
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| Reinhardt D, Houliara K, Pekrun A, Lakomek M, Krone B |
Impact of Conventional Chemotherpy on Levels of Antibodies Against Vaccine-Preventable Diseases in Children Treated for Cancer. |
Scand J Infect Dis 2003, 35: 851 |
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| Reiter A |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Deutschen Gesellschaft für Pädi-atrische Onkologie und Hämatologie: Non-Hodgkin-Lymphome im Kindesalter. |
AWMF online 2003 |
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| Reinhard H, Semler O, Burger D, Bode U, Flentje M, Göbel U, Gutjahr P, Leuschner I, Maass E, Niggli F, Scheel-Walter H, Stockle M, Thuroff J, Troger J, Weirich A, von Schweinitz D, Zoubek A, Graf N |
Results of the SIOP 93-01/GPOH trial and study for the treatment of patients with unilateral nonmetastatic Wilms Tumor. |
Klin Pädiatr 2004, 216: 132 |
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| Reinhardt D, Diekamp S, Fleischhack G, Corbacioglu S, Jürgens H, Dworzak M, Kaspers G, Creutzig U, Zwaan C |
Gemtuzumab Ozogamicin (Mylotarg©) in Children with Refractory or Relapsed Acute Myeloid Leukemia. |
Onkologie 2004, 27: 269 |
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| Reinhardt D, Kurzknabe E, Löffler H, Creutzig U |
Akute Leukämien im Kindesalter mit besonderer Berücksichtigung der morphologischen Diagnostik. |
pädiatrische praxis 2004, 64: 395 |
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| Reinhard H, Aliani S, Ruebe C, Stockle M, Leuschner I, Graf N |
Wilms' tumor in adults: results of the Society of Pediatric Oncology (SIOP) 93-01/Society for Pediatric Oncology and Hematology (GPOH) Study. [+] |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2004, 22: 4500 |
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| PURPOSE: In the Society of Pediatric Oncology (SIOP) 93-01 study, 30 patients older than 16 years were found to have Wilms' tumor. They were treated according to the pediatric protocol and were analyzed for clinical presentation, stage distribution, and prognosis. PATIENTS AND METHODS: Patient age ranged from 16 to 62 years (median, 25.4 years). Tumor stages were defined according to SIOP, and treatment was risk-adapted according to SIOP 93-01/Society for Pediatric Oncology and Hematology (GPOH) protocol. The patients were evaluated with regard to response, toxicity, and prognosis. Specimens of all tumors were centrally reviewed. RESULTS: Ten patients (33%) had metastatic disease at the time of diagnosis (liver, four patients; lung, three patients; liver and lung, three patients). The local stage distribution showed a predominance of higher stages (stage I, eight patients; stage IIN-, three patients; stage IIN+, four patients; stage III, 15 patients). Histologic studies revealed intermediate-risk in 23 of 30 tumors; two tumors were classified as high-risk; and three tumors were clear-cell sarcomas. Two of 30 patients showed a nephroblastoma and a renal cell carcinoma simultaneously in the same kidney. A complete remission was achieved in 24 patients; four patients relapsed after complete remission; and three of them reached a second remission with further treatment. Event-free survival was 57%, with an overall survival of 83% (median observation time, 4 years). CONCLUSION: Adults can be cured in a high percentage by a multimodal treatment according to pediatric protocols. Toxicity is higher than in children, but acceptable in view of the high remission rate. |
| Reinhardt D, Diekamp S, Langebrake C, Ritter J, Stary J, Dworzak M, Schrauder A, Zimmermann M, Fleischhack G, Ludwig WD, Harbott J, Creutzig U |
Acute megakaryoblastic leukemia in children and adolescents, excluding Down's syndrome: improved outcome with intensified induction treatment. |
Leukemia 2005, 19: 1495 |
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| Reinhardt D, Ritter J |
Klassifikation der Leukämien und malignen Lymphome. |
In: Gadner H, Gaedicke G, Niemeyer C, Ritter J, editors. Pädiatrische Hämatologie und Onkologie Berlin, Heidelberg, New York: Springer Verlag, 2006, 647 |
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| Reinhardt D, Ritter J |
Reaktive Veränderungen des Blutbildes und des Knochenmarks. |
In: Gadner H, Gaedicke G, Niemeyer C, Ritter J, editors. Pädiatrische Hämatologie und Onkologie Berlin, Heidelberg, New York: Springer Verlag, 2006, 309 |
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| Reiter A |
Non-Hodgkin-Lymphome im Kindesalter. |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie 2006 |
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| Reiter A, Mann G, Parwaresch R |
Non-Hodgkin-Lymphome. |
In: Gadner H, Gaedicke G, Niemeyer C, Ritter J, editors. Pädiatrische Hämatologie und Onkologie Berlin, Heidelberg, New York: Springer Verlag, 2006, 733 |
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| Reiche R, Herold R |
Strukturen in der Pädiatrischen Onkologie und Hämatologie, Ergebnisse der wissenschaftlichen Begleitung der Jahre 2000 - 2006. |
Js. Karthaus GmbH & Co, Bonn 2007 |
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| Reid S, Schindler D, Hanenberg H, Barker K, Hanks S, Kalb R, Neveling K, Kelly P, Seal S, Freund M, Wurm M, Batish SD, Lach FP, Yetgin S, Neitzel H, Ariffin H, Tischkowitz M, Mathew CG, Auerbach AD, Rahman N |
Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. [+] |
Nat Genet 2007, 39: 162 |
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| PALB2 was recently identified as a nuclear binding partner of BRCA2. Biallelic BRCA2 mutations cause Fanconi anemia subtype FA-D1 and predispose to childhood malignancies. We identified pathogenic mutations in PALB2 (also known as FANCN) in seven families affected with Fanconi anemia and cancer in early childhood, demonstrating that biallelic PALB2 mutations cause a new subtype of Fanconi anemia, FA-N, and, similar to biallelic BRCA2 mutations, confer a high risk of childhood cancer. |
| Reiter A, Klapper W |
Recent advances in the understanding and management of diffuse large B-cell lymphoma in children. [+] |
British journal of haematology 2008, 142: 329 |
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| Diffuse large B-cell lymphomas (DLBCL) are neoplasms of transformed mature B cells, accounting for approximately 10% of non-Hodgkin lymphomas (NHL) of childhood. Increasing evidence indicates that DLBCL are composed of biologically distinct subsets. Clinical features of children with DLBCL differ from those with other NHL entities, e.g. by a lower frequency of bone-marrow and central nervous system involvement. Treatment strategies originally designed for Burkitt lymphoma appear to be efficacious for children with DLBCL. However, children with primary mediastinal large B-cell lymphoma may need a more specific treatment approach, given their inferior outcome in recent studies. The addition of the monoclonal anti-CD20 antibody rituximab to standard CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy improved outcome of adults with DLBCL significantly. However, preliminary data suggest differences between DLBCL of children and adults concerning cell of origin, genetic abnormalities and responsiveness to current treatments. Thus, the potential role of monoclonal antibodies in the treatment of children with DLBCL remains to be determined. The availability of new methodological tools, such as gene expression profiling, will greatly enhance our insights into the biology of childhood DLBCL and its similarities and disparities compared to adult DLBCL. Furthermore, these tools may enable a more risk-adapted and rationally targeted subtype-specific therapy in the future. |
| Reinmuth S, Liebeskind AK, Wickmann L, Bockelbrink A, Keil T, Henze G, Borgmann A |
Having children after surviving cancer in childhood or adolescence - results of a Berlin survey. [+] |
Klinische Padiatrie 2008, 220: 159 |
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| OBJECTIVE: To assess the desire to have children, the actual number of children, and children's health in a survey of 752 adult survivors of paediatric or adolescent cancer in Berlin, Germany. PATIENTS: The German Childhood Cancer Registry ( Deutsches Kinderkrebsregister, DKKR) listed 752 paediatric cancer patients who had been treated in 1 of the 2 paediatric oncology centres in Berlin since 1980 and were 18 years of age or older at the time of the survey. METHODS: A 4-page questionnaire assessing pubertal development, fertility, the desire to have children, the actual number of children, and children's health was sent to 574 former patients located using data from the DKKR and German Residents' Registration Office. RESULTS: In total, 45% (n=260) of patients (140 women, 120 men) returned the questionnaire. The mean age was 10.9 years at the time of diagnosis and 24.3 years at the time of the present survey. Various aspects of puberty were assessed to evaluate pubertal development. Of all study participants, 77% indicated a general desire to have children. Reasons given for not having children included 'Still too early to have children' (67%), 'Fear that my child will develop cancer' (9%), and 'Fear that cancer will recur' (6%). Transient amenorrhoea, lasting from 1 to 30 months, occurred in 25 of 74 patients after chemo- and radiotherapy. Five of 136 participants indicated that they had already reached menopause. Seventeen per cent of all participants or their partners had already been pregnant. The miscarriage rate was 13%. Thirty participants gave birth to or fathered a total of 41 children, of whom 40 were healthy and 1 was born with a foot deformity (Pes equinovarus). Among participants' children, mean weight at birth was 3 458 g, and mean head circumference was 35 cm. DISCUSSION: The desire to have children was lower among our survey participants than in the general population of the same age (77% vs. 90%). Participants' fears that their children might develop cancer or that their own cancer might recur are often unfounded. Paediatric cancer survivors, relatives, and attending physicians should be well informed about this issue by paediatric oncologists. The proportion of miscarriages, mean weight at birth, and mean head circumference at birth in our study were comparable to the German general population. OUTLOOK: We intend to conduct a nationwide survey entitled 'Fertility after Chemo- and Radiotherapy in Paediatric and Adolescent Patients' (FeCt). The aim is to gain valuable data with a larger number of participants and more statistical power to determine whether specific cytotoxic drugs or radiation increase the risk of infertility, and if so, at what doses. For the study, the DKKR has the addresses of more than 5 000 former patients in Germany who are now adults. The results will be used to plan future treatment optimisation studies, and to assess the need for prophylactic measures in cases where fertility-compromising therapies are unavoidable. This nationwide survey 'FeCt' will be supported by the Deutsche Kinderkrebsstiftung. |
| Reinhard H, Reinert J, Beier R, Furtwängler R, Alkasser M, Rutkowski S, Frühwald M, Koscielniak E, Leuschner I, Kaatsch P, Graf N |
Rhabdoid tumors in children: prognostic factors in 70 patients diagnosed in Germany. [+] |
Oncology reports 2008, 19: 819 |
|
| We retrospectively analysed the data of 70 patients (41 boys and 29 girls) with Rhabdoid tumors (RT) regardless of localisation, recorded in the German Childhood Cancer Registry (GCCR) from 1984 to 1999. The primary tumor was located in the kidney in 32 cases, in the central nervous system (CNS) in 13 cases and in the soft tissue in 25 cases. Variables examined were tumor stage, sex, age at diagnosis, surgical radicality, radiotherapy and chemotherapeutic regimens. Metastatic disease at diagnosis was observed in 18 of the 70 individuals. Outcome of this group was very poor with a 5-year overall survival of 11%. There were no differences in survival between males and females, or younger and older children. Chemotherapeutic regimens were mainly given according to the primary site of the tumor. Radiotherapy was given in 28 of the 70 patients with a mean dose of 35 Gray, though this did not improve the outcome. Overall survival of the whole cohort was 27% at 5 years and there was no significant difference in prognosis regarding the different locations of the tumor (kidney 24%, soft tissue 30%, CNS 29%). In conclusion, RT in infants and children has a dismal prognosis, independent from localisation. The presence of metastasis at diagnosis seems to be the only prognostic factor of outcome. |
| Reiter A, Wössmann W |
Non-Hodgkin-Lymphome. |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie 2009 |
|
| Reimann, V |
Stammzellen aus Nabelschnurblut in der Transplantations- und regenerativen Medizin. |
Dtsch Arztebl 2009, 106: 831 |
|
| Reinhardt D, Reinhardt K, Neuhoff C, Sander A, Klusmann JH, Pekrun A, Sauerbrey A, von Stackelberg A, Rössig C, Creutzig U, Kolenova A |
[GATA1-Mutation Associated Leukemia in Children with Trisomy 21 Mosaic]. [+] |
Klinische Padiatrie 2012, 224: 153 |
|
| Mutations of the hematopoietic trans-cription factor GATA1 (GATA1s) are pathognomonic in newborn with transient leukemia and children with Down syndrome and myeloid leukemia (ML-DS). Both TL and ML-DS can also occur in children with trisomy 21 mosaic.Between 2002 and 2011, 15 newborns and infants were diagnosed with DS mosaic. 9 of them presented with TL and 8 children suffered from ML-DS; 2 of them with a history of TL. In children without stigmata the special morphology and immunophenotype of blasts triggered the screening for GATA1 mutation and trisomy 21 mosaic.All newborns with TL achieved complete remission (CR). Due to clinical symptoms caused by the leukemic blasts, in 3 children low-dose cytarabine was applied. 1 patient died due to cardiac defect. In all patients GATA 1 s was confirmed. 6 children with ML-DS were initially treated according the AML-BFM protocol. After ML-DS was confirmed, therapy was continued with the intensity reduced schedule according to the ML-DS 2006 protocol. All children are still in CR (follow-up 1.8-7 years, median 2.7 yrs). 2 children with unknown trisomy 21 mosaic were diagnosed as acute megakaryoblastic leukemia (AMKL) and treated according the high risk arm of the AML-BFM 2004 including allogeneic stem cell transplantation in one child). GATA1 muta-tion was identified retrospectively. Both children are alive in CR.GATA1s associated leukemia has to be excluded in all young children with AMKL (<5years old) to prevent overtreatment. Treatment with reduced intensity seems sufficient in children trisomy 21 mosaic and ML-DS. |
| Reinhardt D, Von Neuhoff C, Sander A, Creutzig U |
[Genetic Prognostic Factors in Childhood Acute Myeloid Leukemia.] [+] |
Klinische Padiatrie 2012 Jul 20; |
|
| The survival rate of children and adolescents suffering acute myeloid leukemia (AML) has been significantly improved within the last decades. This has been achieved by a continuously intensified therapy and progress in supportive care to prevent and treat complications. In Germany, the AML-BFM trials 98 (n=413) and 2004 (n=499) enrolled 912 children and adolescents as protocol patients (1998-2010). The 5-year-overall survival was 71±2%. In the previous studies prognosis and subsequent treatment stratification based on morphology, cytochemistry and white blood cell count. Today, the identification of new genetic aberrations in AML enables a genetically determined estimation of prognosis, although treatment response must be considered for treatment stratification. The group with a favorable prognosis summarized AML with t(8;21), inv(16), t(15;17), t(1;11), and AML with normal karyotype and NPM1-mutation (n=253; EFS 74±3%, OS 88±2%). A poor prognosis (HR-group) must be expected in AML with t(4;11), t(5;11), t(6;11), t(6;9), t(7;12), t(9;22), Monosomy 7, combined FLT3/WT1-mutation, and AML with der(12p)-aberration (n=101; EFS 30±5%; OS 56±5%). The intermediate group summarizes all other subgroups especially AML with normal karyotyp, AML with FLT3-ITD or t(9;11) (n=558; EFS 43±2%; OS 64±2%). The validation of the internationally identified, genetically determined prognostic factors within the AML-BFM (Germany) study population will support treatment recommendations. |
| Remke M, Pfister S, Kox C, Toedt G, Becker N, Benner A, Werft W, Breit S, Liu S, Engel F, Wittmann A, Zimmermann M, Stanulla M, Schrappe M, Ludwig WD, Bartram CR, Radlwimmer B, Muckenthaler MU, Lichter P, Kulozik AE |
High-resolution genomic profiling of childhood T-ALL reveals frequent copy-number alterations affecting the TGF-beta and PI3K-AKT pathways and deletions at 6q15-16. 1 as a genomic marker for unfavorable early treatment response. [+] |
Blood 2009, 114: 1053 |
|
| Precursor T-cell acute lymphoblastic leukemia (T-ALL) in children represents a clinical challenge, because relapses are usually fatal. It is thus necessary to identify high-risk patients as early as possible to effectively individualize treatment. We aimed to define novel molecular risk markers in T-ALL and performed array-based comparative genomic hybridization (array-CGH) and expression analyses in 73 patients. We show that DNA copy-number changes are common in T-ALL and affect 70 of 73 (96%) patients. Notably, genomic imbalances predicted to down-regulate the TGF-beta or up-regulate the PI3K-AKT pathways are identified in 25 of 73 (34%) and 21 of 73 (29%) patients, suggesting that these pathways play key roles in T-ALL leukemogenesis. Furthermore, we identified a deletion at 6q15-16.1 in 9 of 73 (12%) of the patients, which predicts poor early treatment response. This deletion includes the CASP8AP2 gene, whose expression is shown to be down-regulated. The interaction of CASP8AP2 with CASP8 plays a crucial role in apoptotic regulation, suggesting a functional link between the clinical effect of the deletion and the molecular mode of action. The data presented here implicate the TGF-beta and PI3K-AKT pathways in T-ALL leukemogenesis and identify a subgroup of patients with CASP8AP2 deletions and poor early treatment response. |
| Renella R, Wood WG |
The congenital dyserythropoietic anemias. [+] |
Hematology/oncology clinics of North America 2009, 23: 283 |
|
| The congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of hereditary disorders that seem to be restricted to the erythroid lineage. They are characterized by morphologic abnormalities of erythroid precursors in the bone marrow, resulting in ineffective erythropoiesis and a suboptimal reticulocyte response. As with many rare disorders, cases of CDA are often misdiagnosed, which may lead to inappropriate management. In this review, the authors highlight the relevant clinical data together with recent molecular advances that should aid decision making in diagnosis and patient management. |
| Rendtorff R, Beyer M, Müller A, Dittrich R, Hohmann C, Keil T, Henze G, Borgmann A |
Low inhibin B levels alone are not a reliable marker of dysfunctional spermatogenesis in childhood cancer survivors. [+] |
Andrologia 2011, [Epub ahead of print] |
|
| Hormone and semen analyses were carried out to examine the diagnostic value of hormones and hormone combinations as markers of spermatogenesis in male patients who had received oncological treatment in childhood. Hormone analyses from 73 participants and spermiograms from 42 participants were evaluated. Spearman's correlation coefficients and measures of diagnostic accuracy were calculated for the hormone and semen analysis values. Inhibin B levels of <80 ml/ml, follicle-stimulating hormone (FSH) levels of >10 IU l(-1) and a combination of the two parameters showed positive predictive values for azoospermia of 0.423, 0.6154 and 0.6667 respectively. While 32% of the 73 participants showed a combination of abnormal inhibin B and FSH values, which strongly indicates impaired spermatogenesis, 31% of the 42 spermiogram results revealed azoospermia. The hormone and semen analyses showed that approximately one-third of the participants had fertility impairment. Inhibin B alone thus does not reflect spermatogenesis as well as inhibin B in combination with FSH in patients who have undergone cancer treatment in childhood. Both parameters should therefore be evaluated in paediatric cancer follow-up programmes to allow better identification of treatment regimens that cause persistent azoospermia in male childhood cancer survivors. |
| Rickert CH, Strater R, Kaatsch P, Wassmann H, Jürgens H, Dockhorn-Dworniczak B, Paulus W |
Pediatric high-grade astrocytomas show chromosomal imbalances distinct from adult cases. |
Am J Pathol 2001, 158: 1525 |
|
| Rieden K, Weirich A, Tröger J, Ludwig R |
Tumor response to pre-operative chemotherapy in nephroblastoma. |
Advanced radiation therapy, tumor response monitoring and treatment planning 1992, 249 |
|
| Rieden K, Weirich A, Tröger J, Gamroth H, Raschke K, Ludwig R |
Accuracy of diagnostic imaging in nephroblastoma before preoperative chemotherapy. |
Eur Radiol 1993, 3: 115 |
|
| Riede UN (Hrsg) |
Allgemeine und spezielle Pathologie. |
Georg-Thieme-Verlag 5. komplett überarb. Aufl., 2004 |
|
| Ritter J, Creutzig U, Riehm H, Schellong G |
Acute myelogenous leukemia. |
Recent Results Cancer Res 1984, 93: 204 |
|
| Ritter J, Creutzig U, Riehm H, Brandeis W, Gerein V, Prindull G, Rister M, Schellong G |
Improved treatment results in childhood acute myelogenous leukemia. |
Haematology and Blood Transfusion 1985, 29: 82 |
|
| Ritter J, Creutzig U, Schellong G |
Risikogruppen bei der akuten, nicht-lymphatischen Leukämie im Kindesalter. Analyse der Ergebnisse der kooperativen Therapiestudien AML-BFM-78 and 83. |
Onkologie 1986, 9: 78 |
|
| Ritter J, Creutzig U, Henze G, Jürgens H, Bode U, Prindull G, Schellong G |
High dosage ARA-C in combination with mitoxantrone in therapy of acute myeloid leukemia in childhood. Initial results of the AML BFM-85 recurrence study. |
Onkologie 1987, 10: 24 |
|
| Ritter J, Creutzig U, Hiddemann W, Schellong G |
Mitoxantron in Kombination mit hochdosiertem ARA-C als Therapiemöglichkeit bei der AML im Kindesalter. |
Fortschr antimikr antineoplast Chemother 6-9 1987, 1517-1521, 1987 |
|
| Ritter J, Voigt D, Hoese G, Schellong G |
Special aspects of supportive therapy in childhood acute leukemias. |
Haematol Bluttransfus 1987, 30: 182 |
|
| Ritter J |
Diagnostik und Therapie der akuten Leukämien. |
Onkol Forum Chemotherapie 1988, 2: 1 |
|
| Ritter J, Vormoor J, Creutzig U, Schellong G |
Prognostic significance of Auer rods in childhood acute myelogenous leukemia. |
Med Pediatr Oncol 1989, 17: 202 |
|
| Ritter J, Creutzig U, Jobke A, Lampert F, Reiter A, Schellong G |
Acute myelogenous leukemia in the first year of life. |
Contrib Oncol 1990, 41: 30 |
|
| Ritter J, Creutzig U, Reiter A, Riehm H, Schellong G |
Childhood leukemia. |
J Cancer Res Clin Oncol 1990, 116: 100 |
|
| Ritter J, Creutzig U, Schellong G |
Improved treatment results in the myelocytic subtypes FAB M1- M4 but not in FAB M5 after intensification of induction therapy. |
Haematology and Blood Transfusion 1990, 33: 185 |
|
| Ritterbach J, Harbott J, Ritter J, Lampert F |
Chromosomal aberrations in childhood acute nonlymphoblastic leukemia. |
Hamatol Bluttransfus 1990, 33: 153 |
|
| Ritter J, Creutzig U, Schellong G |
Treatment results of three consecutive German childhood AML trials. |
Leukemia 1992, 6: 59 |
|
| Ritter J, Creutzig U, Schellong G, Group for |
Treatment of refractory and relapsed childhood acute myelogenous leukemia with high dose cytosine arabinoside and mitoxantrone (HAM). |
Haematology and Blood Transfusion 1992, 34: 418 |
|
| Ritter J |
Diagnostic and therapy of systemic fungal infections in children with hematological malignancies. |
Res Clin Oncol 1994, 120 |
|
| Ritter J, Roos N |
Special aspects related to invasive fungal infections in children with cancer. |
Bailliere's Clin Inf Dis 1995, 2: 179 |
|
| Ritter J, Creutzig U, Zimmermann M |
The specific role of Idarubicin during Induction therapy of childhood AML. |
Haematology and Blood Transfusion 1996, 38: 396 |
|
| Ritter J |
Acute myeloid leukaemias. |
Eur J Cancer 1998, 34: 862 |
|
| Ritterbach J, Hiddemann W, Beck J, Schrappe M, Janka-Schaub G, Ludwig W, Harbott J, Lampert F |
Detection of hyperdiploid karyotypes (>50 chromosomes) in childhood acute lymphoblastic leukemia (ALL) using fluorescence in situ hybridization (FISH). |
Leukemia 1998, 12: 427 |
|
| Ritter J, Schrappe M |
Theray of lymphoblastic leukemia. |
Paediatric Haematology 1999 |
|
| Roach ES, Gomez MR, Northrup H |
Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. |
J Child Neurol 1998, 83: 624-8. |
|
| Robison LL, Buckley JD, Daigle AE, Wells R, Benjamin D, Arthur DC, Hammond GD |
Maternal drug use and risk of childhood nonlymphoblastic leukemia among offspring. An epidemiologic investigation implicating marijuana (a report from the Childrens Cancer Study Group). |
Cancer 1989, 63: 1904 |
|
| Rodriguez T, Baumgarten E, Fengler R, Soumpasis D, Henze G |
Long-term infusion of L-asparaginase--an alternative to intramuscular injection? |
Klin Pädiatr 1995, 207: 207 |
|
| Rodl R, Hoffmann C, Gosheger G, Leidinger B, Jürgens H, Winkelmann W |
Ewing's sarcoma of the pelvis. |
J Surg Oncol 2003, 83: 154 |
|
| Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kühne T, Ruggeri M, George JN |
Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. [+] |
Blood 2009, 113: 2386 |
|
| Diagnosis and management of immune thrombocytopenic purpura (ITP) remain largely dependent on clinical expertise and observations more than on evidence derived from clinical trials of high scientific quality. One major obstacle to the implementation of such studies and in producing reliable meta-analyses of existing data is a lack of consensus on standardized critical definitions, outcome criteria, and terminology. Moreover, the demand for comparative clinical trials has dramatically increased since the introduction of new classes of therapeutic agents, such as thrombopoietin receptor agonists, and innovative treatment modalities, such as anti-CD 20 antibodies. To overcome the present heterogeneity, an International Working Group of recognized expert clinicians convened a 2-day structured meeting (the Vicenza Consensus Conference) to define standard terminology and definitions for primary ITP and its different phases and criteria for the grading of severity, and clinically meaningful outcomes and response. These consensus criteria and definitions could be used by investigational clinical trials or cohort studies. Adoption of these recommendations would serve to improve communication among investigators, to enhance comparability among clinical trials, to facilitate meta-analyses and development of therapeutic guidelines, and to provide a standardized framework for regulatory agencies. |
| Rodeghiero F, Ruggeri M |
Short- and long-term risks of splenectomy for benign haematological disorders: should we revisit the indications? [+] |
British journal of haematology 2012l; 158: 16 |
|
| Splenectomy has represented a key treatment option in the treatment of many benign haematological diseases, including immune thrombocytopenia (ITP) and disorders associated with ongoing haemolysis (thalassaemia major and intermedia, sickle cell disease, and hereditary or acquired haemolytic anaemias). Improvements in surgical techniques have reduced perioperative complications and mortality. Preventive measures (new protein conjugate vaccines, antibiotic prophylaxis, and increased vigilance) are thought to greatly reduce the risk of overwhelming post-splenectomy infection (OPSI), although their implementation is inconsistent. Nevertheless, there is increasing documentation of the short- and long-term risks of splenectomy, which vary according to the underlying indication. Splenectomized patients are at increased risk of venous thromboembolism, particularly within the splenoportal system. The long-term thromboembolic risk is higher in haematological disorders associated with ongoing haemolysis, particularly in thalassaemia intermedia, which has led to a more conservative approach. In comparison, patients with ITP appear to be at lower risk of adverse effects of splenectomy, which maintains its place as the potentially most curative and safe second-line treatment. However, a splenectomy-sparing approach is also emerging for ITP, and recent guidelines recommend that this procedure is deferred until ≥12 months from ITP diagnosis, to allow sufficient time for possible remission. |
| Roessner A, Jürgens H |
Round cell tumours of bone. |
Pathol Res Pract 1993, 189: 111 |
|
| Rogge T, Niemeyer C |
Myelodysplastic syndromes in childhood. |
Onkologie 2000, 23: 18 |
|
| Rohrschneider W, Weirich A, Rieden K, Darge K, Troger J, Graf N |
US, CT and MR imaging characteristics of nephroblastomatosis. |
Pediatr Radiol 1998, 28: 435 |
|
| Rokes CA, Remke M, Guha-Thakurta N, Witt O, Korshunov A, Pfister S, Wolff JE |
Sorafenib plus valproic acid for infant spinal glioblastoma. [+] |
J Pediatr Hematol Oncol 2010, 32: 511 |
|
| SUMMARY: Spinal glioblastoma multiforme (GBM) is rare in children. New therapeutic options should be explored given the poor outcomes reported. We describe the case of an infant with spinal GBM whose condition worsened despite radiotherapy and chemotherapy. Immunohistochemical analysis of the tumor sample showed activation of the Raf-MEK-ERK pathway. Targeted pharmacologic therapy with sorafenib plus valproic acid led to decrease in the size of the tumor and improvement of symptoms. We conclude that regulation of the mitogen-activated protein kinase pathway using sorafenib plus valproic acid warrants further investigation for the management of childhood GBM. |
| Romanowski R, Schott C, Issels R, Klingebiel T, Treuner J, Jürgens H, Göbel U, Goldschmitt-Wuttge B, Feldmann H, Haas R |
Regional hyperthermia with systemic chemotherapy in children and adolescents. |
Klinische Pädiatrie 1993, 205: 249 |
|
| Rossi R, Helmchen U, Schellong G |
Tubular function and histological findings in ifosfamide-induced renal Fanconi syndrome--a report of two cases. |
Eur J Pediatr 1992, 151: 384 |
|
| Rossi R, Ehrich J |
Partial and complete de Toni-Debre-Fanconi syndrome after ifosfamide chemotherapy of childhood malignancy. |
Eur J Clin Pharmacol 1993, 44 Suppl 1:S43-5:S43-S45 |
|
| Rossi R, Kleinebrand A, Godde A, Rath B, Jürgens H |
Increased risk of ifosfamide-induced renal Fanconi's syndrome after unilateral nephrectomy [letter]. |
Lancet 1993, 341 |
|
| Rossi R, Rath B, Ullrich K, Ehrich J |
Ifosfamide-induced nephrotoxicity. |
Monatsschr Kinderheilkd 1993, 141: 594 |
|
| Rossi R, Danzebrink S, Hillebrand D, Linnenburger K, Ullrich K, Jürgens H |
Ifosfamide-induced subclinical nephrotoxicity and its potentiation by cisplatinum. |
Med Pediatr Oncol 1994, 22: 27 |
|
| Rossi R, Danzebrink S, Linnenburger K, Hillebrand D, Gruneberg M, Sablitzky V, Deufel T, Ullrich K, Harms E |
Assessment of tubular reabsorption of sodium, glucose, phosphate and amino acids based on spot urine samples. |
Acta Paediatr 1994, 83: 1282 |
|
| Rossi R, Godde A, Kleinebrand A, Riepenhausen M, Boos J, Ritter J, Jürgens H |
Unilateral nephrectomy and cisplatin as risk factors of ifosfamide-induced nephrotoxicity. |
J Clin Oncol 1994, 12: 159 |
|
| Rossi R, Kist C, Wurster U, Kulpmann W, Ehrich J |
Estimation of ifosfamide/cisplatinum-induced renal toxicity by urinary protein analysis. |
Pediatr Nephrol 1994, 8: 151 |
|
| Rossi R, Godde A, Kleinebrand A, Rath B, Jürgens H |
Concentrating capacity in ifosfamide-induced severe renal dysfunction. |
Ren Fail 1995, 17: 551 |
|
| Rossi R |
Nephrotoxicity of ifosfamide--moving towards understanding the molecular mechanisms [editorial]. |
Nephrol Dial Transplant 1997, 12: 1091 |
|
| Rossi R, Schäfers P, Pleyer J, Postler Ch, Boos J, Jürgens H |
The influence of short versus continious ifosfamide infusion on the development of renal tubular impairment. |
J Ped Hematol/Oncol 1997, 4: 393 |
|
| Rossi R, Kleta R, Ehrich J |
Renal involvement in children with malignancies. |
Pediatr Nephrol 1999, 13: 153 |
|
| Rossi R, Pleyer J, Schäfers P, Kuhn N, Kleta R, Deufel T, Jürgens H |
Development of ifosfamide-induced nephrotoxicity. |
Med Pediatr Oncol 1999, 32: 177 |
|
| Rosenthal H, Kolb R, Gratz K, Reiter A, Galanski M |
Bone manifestations in non-Hodgkin's lymphoma in childhood and adolescence. |
Radiologe 2000, 40: 737 |
|
| Rosthøj S, Hedlund-Treutiger I, Rajantie J, Zeller B, Jonsson OG, Elinder G, Wesenberg F, Henter JI, NOPHO ITP Working Group |
Duration and morbidity of newly diagnosed idiopathic thrombocytopenic purpura in children: A prospective Nordic study of an unselected cohort. [+] |
The Journal of pediatrics 2003, 143: 302 |
|
| To determine the duration of the risk period with platelet counts <20 x 10(9)/L and the frequency of bleeding episodes in unselected children with idiopathic thrombocytopenic purpura (ITP). |
| Rosenberg PS, Alter BP, Bolyard AA, Bonilla MA, Boxer LA, Cham B, Fier C, Freedman M, Kannourakis G, Kinsey S, Schwinzer B, Zeidler C, Welte K, Dale DC, Severe Chronic Neutropenia International Registry |
The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. [+] |
Blood 2006, 107: 4628 |
|
| In patients with severe congenital neutropenia (SCN), sepsis mortality is reduced by treatment with granulocyte colony-stimulating factor (G-CSF), but myelodsyplastic syndrome and acute myeloid leukemia (MDS/AML) have been reported. We studied 374 patients with SCN and 29 patients with Shwachman-Diamond syndrome (SDS) on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. In SCN, sepsis mortality was stable at 0.9% per year. The hazard of MDS/AML increased significantly over time, from 2.9% per year after 6 years to 8.0% per year after 12 years on G-CSF. After 10 years, the cumulative incidence was 8% for sepsis mortality and 21% for MDS/AML. A subgroup of SCN patients (29%) received more than the median dose of G-CSF (> or = 8 microg/kg/d), but achieved less than the median absolute neutrophil count (ANC) response (ANC < 2.188 x 10(9)/L [2188/microL] at 6-18 months). In these less-responsive patients, the cumulative incidence of adverse events was highest: after 10 years, 40% developed MDS/AML and 14% died of sepsis, compared with 11% and 4%, respectively, of more responsive patients whose ANC was above the median on doses of G-CSF below the median. Risk of MDS/AML may be similar in SDS and SCN. In less-responsive SCN patients, early hematopoietic stem cell transplantation may be a rational option. |
| Rosenberg PS, Zeidler C, Bolyard AA, Alter BP, Bonilla MA, Boxer LA, Dror Y, Kinsey S, Link DC, Newburger PE, Shimamura A, Welte K, Dale DC |
Stable long-term risk of leukaemia in patients with severe congenital neutropenia maintained on G-CSF therapy. [+] |
British journal of haematology 2010, 150: 196 |
|
| In severe congenital neutropenia (SCN), long-term therapy with granulocyte colony-stimulating factor (G-CSF) has reduced mortality from sepsis, revealing an underlying predisposition to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We have reported the early pattern of evolution to MDS/AML, but the long-term risk remains uncertain. We updated a prospective study of 374 SCN patients on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. Long-term, the annual risk of MDS/AML attained a plateau (2.3%/year after 10 years). This risk now appears similar to, rather than higher than, the risk of AML in Fanconi anaemia and dyskeratosis congenita. |
| Roth H, Weirich A, Ludwig R, Daum R, Zimmermann H |
Resection of nephroblastoma. |
Langenbecks Arch Chir Suppl Kongressbd 1996, 113: 1078 |
|
| Rots M, Pieters R, Peters G, Noordhuis P, van Zantwijk C, Kaspers G, Hählen K, Creutzig U, Veerman A, Jansen G |
Circumvention of methotrexate resistance in childhood leukemia subtypes by rationally designed antifolates. |
Blood 1999, 54: 3121 |
|
| Rots M, Pieters R, Peters G, Noordhuis P, van Zantwijk C, Kaspers G, Hählen K, Creutzig U, Veerman A, Jansen G |
Role of folylpolyglutamate synthetase and folylpolyglutamate hydrolase in methotrexate accummulation and polyglutamylation in childhood leukemia. |
Blood 1999, 93: 1677 |
|
| Rots M, Pieters R, Peters G, Noordhuis P, van Zantwijk C, Henze G, Janka-Schaub G, Veerman A, Jansen G |
Methotrexate resistance in relapsed childhood acute lymphoblastic leukaemia. |
Br J Haematol 2000, 109: 629 |
|
| Rots M, Pieters R, Peters G, Noordhuis P, van Zantwijk C, Henze G, Janka-Schaub G, Veerman A, Jansen G |
Methotrexate resistance in relapsed childhood acute lymphoblastic leukaemia. |
Br J Haematol 2000, 109: 629 |
|
| Rots M, Pieters R, Jansen G, Kaspers G, van Zantwijk C, Noordhuis P, Voorn D, van Wering E, Creutzig U, Veerman A, Peters G |
A possible role for methotrexate in the treatment of childhood acute myeloid leukaemia, in particular for acute monocytic leukaemia. |
Eur J Cancer 2001, 37: 492 |
|
| Roth CL, Hunneman DH, Gebhardt U, Stoffel-Wagner B, Reinehr T, Müller HL |
Reduced sympathetic metabolites in urine of obese patients with craniopharyngioma. [+] |
Pediatr Res 2007, 61: 496 |
|
| Severe obesity is a major problem in patients suffering from craniopharyngioma (CP), a benign tumor located in pituitary and hypothalamic regions. In this study, the hypothesis that hypothalamic damage leads to a reduction in overall sympathetic tone was tested. Catecholamines, as well as their metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA), markers of catecholamine turnover, were measured in morning voided urine of 109 patients participating in a German pediatric CP study, and their physical activity was analyzed using a questionnaire. HVA and VMA results were compared with age-matched HVA and VMA in urine of patients proven to not have a catecholamine-secreting tumor. Patients with the most severe obesity displayed the lowest urine HVA and VMA values. Patients with hypothalamic CP had 3.2-fold higher BMI values (p<0.0001), lower HVA (0.72-fold, p<0.001), and VMA (0.84-fold, p<0.01) values, and significantly lower activity scores than those without hypothalamic involvement, but their epinephrine- and norepinephrine/creatinine ratios were not significantly different, possibly due to low levels. The low HVA and VMA values suggest decreased sympathetic outflow contributing to reduced physical activity and severe obesity, especially in patients with a hypothalamic tumor. In further studies investigating treatment options for hypothalamic obesity, disturbed sympathetic tone should be considered. |
| Roth CL, Gebhardt U, Müller HL |
Appetite-regulating hormone changes in patients with craniopharyngioma. [+] |
Obesity 2011, 19: 36 |
|
| Patients with craniopharyngioma (CP), an embryological tumor located in the hypothalamic and/or pituitary region, often suffer from uncontrolled eating and severe obesity. We aimed to compare peripherally secreted hormones involved in controlling food intake in normal weight and obese children and adolescents with CP vs. controls. Plasma insulin, glucose, total ghrelin, and peptide-YY (PYY) levels were assessed under fasting conditions as well as 60 min after liquid mixed meal in four groups: Normal weight (n = 12) and obese (n = 15) CP patients, and 12 normal weight and 15 obese otherwise healthy BMI-, gender- and age-matched controls. Homeostasis model assessment of insulin resistance (HOMA(IR)), as well as quantitative insulin sensitivity check index (QUICKI) were calculated. Obese CP subjects had significantly higher HOMA(IR), higher baseline and postmeal insulin but lower ghrelin levels, weaker postmeal changes for PYY, and lower QUICKI compared to obese controls. QUICKI data from all CP patients correlated positively with ghrelin and PYY % postmeal changes (ghrelin: r = 0.38, P = 0.023; PYY r = 0.40, P = 0.017) and negatively with standard deviation score-BMI (SDS-BMI: r = -0.49, P = 0.002). Tumor growth of 87% obese and 58% of normal weight CP patients affected the hypothalamic area which was associated with higher SDS-BMI and weaker % postmeal ghrelin changes (P = 0.014) compared to CP patients without hypothalamic tumor involvement. Blunted postmeal ghrelin and PYY responses in obese CP subjects are likely due to their higher degree of insulin resistance and lower insulin sensitivity compared to matched obese controls. Thus, insulin resistance in CP patients seems to affect eating behavior by affecting meal responses of gut peptides. |
| Royer-Pokora B, Graf N |
Wilms tumors arising at young age: a genetic basis to distinguish subgroups for individualized therapy. |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2011 Jun 1; 29:e485-6; author reply e487 |
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| Rube C, van Valen F, Wilfert F, Palm J, Schuck A, Willich N, Winkelmann W, Jürgens H, Rube C |
Ewing's sarcoma and peripheral primitive neuroectodermal tumor cells produce large quantities of bioactive tumor necrosis factor-alpha (tnf-alpha) after radiation exposure. |
Int J Radiat Oncol Biol Phys 2003, 56: 1414 |
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| Rudolph P, Lappe T, Hero B, Berthold F, Parwaresch R, Harms D, Schmidt D |
Prognostic significance of the proliferative activity in neuroblastoma. |
Am J Pathol 1997, 150: 133 |
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| Rudnik-Schoneborn S, Anhuf D, Koscielniak E, Zerres K |
Alveolar rhabdomyosarcoma in infantile spinal muscular atrophy: coincidence or predisposition? [+] |
Neuromuscular disorders 2005, 15: 45 |
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| We report two unrelated patients with infantile spinal muscular atrophy (SMA) types II and IIIa who developed alveolar rhabdomyosarcoma (ARMS) at 15 and 19 years, respectively. The tumours were located in the forearm, within severely atrophic flexor muscles. They displayed a similar histology and shared the most common translocation, t(2;13)(q35;14) in ARMS. Since cell proliferation is increased in de- and regenerating muscle and the PAX3/FKHR fusion protein activates myogenic transcription, it is tempting to speculate whether severe muscle atrophy in SMA might predispose to malignant transformation in long-standing disease. |
| Rühl U, Albrecht M, Dieckmann K, Lüders H, Marciniak H, Schellenberg D, Wickmann L, Dörffel W |
Response-adapted radiotherapy in the treatment of pediatric Hodgkin's disease. |
Int J Radiation Oncology Biol Phys 2001, 51: 1209 |
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| Ruggeri A, Michel G, Dalle JH, Caniglia M, Locatelli F, Campos A, Diaz de Heredia C, Mohty M, Perez Hurtado JM, Bierings M, Bittencourt H, Mauad M, Purtill D, Cunha R, Kabbara N, Gluckman E, Labopin M, Peters C, Rocha V |
Impact of pre-transplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission. An Eurocord, PDWP-EBMT analysis. [+] |
Leukemia 2012, [Epub ahead of print] |
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| To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen.Seventy-two (43%) were in first CR (CR1), 77 (45%) in second CR (CR2) and 21 (12%) in third CR (CR3). The median interval from MRD quantification to UCBT was 18 days. All patients received single-unit UCBT. Median follow-up was 4 years.Cumulative incidence (CI) of day-60 neutrophil engraftment was 85%. CI of 4-years relapse was 30%, incidence being lower in patients with negative MRD before UCBT (Hazard Risk, HR=0.4, p=0.01) and for those transplanted in CR1 and CR2 (HR=0.3, p=0.002). Probability of 4-years leukemia-free-survival (LFS) was 44%, (56%, 44% and 14% for patients transplanted in CR1, CR2 and CR3, respectively (p=0.0001)). Patients with negative MRD before UCBT had better LFS after UCBT compared to those with positive MRD (54% vs 29%; HR=2, p=0.003).MRD assessment before UCBT for children with ALL in remission allows identifying patients at higher risk of relapse after transplantation. Approaches which may decrease relapse incidence in children given UCBT with positive MRD should be investigated to improve final outcomes.Leukemia accepted article preview online, 4 May 2012; doi:10.1038/leu.2012.123. |
| Ruhnke M, Rickerts V, Cornely OA, Buchheidt D, Glöckner A, Heinz W, Höhl R, Horré R, Karthaus M, Kujath P, Willinger B, Presterl E, Rath P, Ritter J, Glasmacher A, Lass-Flörl C, Groll AH |
Diagnosis and therapy of Candida infections: joint recommendations of the German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy. |
Mycoses 2011 54: 279 |
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| Rund D, Rachmilewitz E |
Beta-thalassemia. |
The New England journal of medicine 2005, 353: 1135 |
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| Rutkowski S, De Vleeschouwer S, Kaempgen E, Wolff JE, Kühl J, Demaerel P, Warmuth-Metz M, Flamen P, Van Calenbergh F, Plets C, Sörensen N, Opitz A, Van Gool SW |
Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study. |
Br J Cancer 2004, 91: 1656 |
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| Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J |
Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. [+] |
The New England journal of medicine 2005, 352: 978 |
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| BACKGROUND: The prognosis for young children with medulloblastoma is poor, and survivors are at high risk for cognitive deficits. We conducted a trial of the treatment of this brain tumor by intensive postoperative chemotherapy alone. METHODS: After surgery, children received three cycles of intravenous chemotherapy (cyclophosphamide, vincristine, methotrexate, carboplatin, and etoposide) and intraventricular methotrexate. Treatment was terminated if a complete remission was achieved. Leukoencephalopathy and cognitive deficits were evaluated. RESULTS: Forty-three children were treated according to protocol. In children who had complete resection (17 patients), residual tumor (14), and macroscopic metastases (12), the five-year progression-free and overall survival rates (+/-SE) were 82+/-9 percent and 93+/-6 percent, 50+/-13 percent and 56+/-14 percent, and 33+/-14 percent and 38+/-15 percent, respectively. The rates in 31 patients without macroscopic metastases were 68+/-8 percent and 77+/-8 percent. Desmoplastic histology, metastatic disease, and an age younger than two years were independent prognostic factors for tumor relapse and survival. Treatment strategies at relapse were successful in 8 of 16 patients. There were no major instances of unexpected toxicity. In 19 of 23 children, asymptomatic leukoencephalopathy was detected by magnetic resonance imaging. After treatment, the mean IQ was significantly lower than that of healthy controls within the same age group but higher than that of patients in a previous trial who had received radiotherapy. CONCLUSIONS: Postoperative chemotherapy alone is a promising treatment for medulloblastoma in young children without metastases. |
| Rutkowski S, Warmuth-Metz M, Sörensen N, Faldum A, Pietsch T, Müller H, Gnekow A, Göbel U, Wolff J, Fleischhack G, Kortmann R |
Hirntumoren im Kindesalter. Diagnostik und interdisziplinäre Therapiekonzepte. |
Der Onkologe Band 2005, Heft 10, |
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| Rutkowski S |
Current treatment approaches to early childhood medulloblastoma. [+] |
Expert Rev Neurother 2006, 6: 1211 |
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| Treatment of medulloblastoma, the most common malignant brain tumor of childhood, is particularly challenging in very young children, owing to the increased susceptibility of the immature brain to treatment-induced neurocognitive deficits. Three promising strategies have been developed in combination with systemic postoperative chemotherapy, to avoid craniospinal irradiation for young children with nonmetastatic medulloblastoma, these include: high-dose chemotherapy, with and without local radiotherapy; intraventricular chemotherapy; and local radiotherapy. More intensified strategies may be required for metastatic medulloblastoma. Future studies will clarify the prognostic relevance of desmoplasia, postoperative residual tumor and biological markers to improve stratification criteria by risk-adapted treatment recommendations. An international Phase III trial for young children with nonmetastatic medulloblastoma, comparing survival rates and neurocognitive outcomes of different treatment strategies by standardized criteria, is under discussion. |
| Rutkowski S |
Timely identification of suspected paediatric CNS tumours. |
The lancet oncology 2007, 8: 664 |
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| Rutkowski S, von Bueren A, von Hoff K, Hartmann W, Shalaby T, Deinlein F, Warmuth-Metz M, Soerensen N, Emser A, Bode U, Mittler U, Urban C, Benesch M, Kortmann RD, Schlegel PG, Kuehl J, Pietsch T, Grotzer M |
Prognostic relevance of clinical and biological risk factors in childhood medulloblastoma: results of patients treated in the prospective multicenter trial HIT'91. [+] |
Clinical cancer research 2007, 13: 2651 |
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| PURPOSE: To identify better risk stratification systems in childhood medulloblastoma based on clinical factors and analysis of routinely processed formalin-fixed tumor material. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tumor samples from well-documented patients treated within the prospective randomized multicenter trial HIT'91 were analyzed for DNA amplification of c-myc and N-myc (n=133) and mRNA expression of c-myc and trkC (n=104; compared with human cerebellum) using validated methods of quantitative PCR and reverse transcription-PCR. Results were related to clinical data and outcome. RESULTS: TrkC and c-myc mRNA expression were identified as independent prognostic factors by multivariate analysis. Three risk groups were identified. (a) Favorable risk group: all 8 patients (2 metastatic) with high trkC (>1x human cerebellum) and low c-myc mRNA expression ( |
| Rutkowski S, Riehle E |
Access to employment and economic independence in cerebral palsy. [+] |
Physical medicine and rehabilitation clinics of North America 2009, 20: 535 |
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| The employment statistics for people with disabilities are dismal and particularly low for those with cerebral palsy. As practitioners working with young people who have moderate to severe cognitive and physical challenges, including those with cerebral palsy, the authors assert that there are best practices that make a difference. There are states and programs showing successful outcomes. Those who create partnerships among education, businesses, and rehabilitation agencies are seeing direct positive results in employment outcomes for people with disabilities, as well as cultural and perceptional changes in businesses and people who have hiring capability. This article reviews the relevant literature; conclusions are drawn and recommendations made to improve the employment outcomes for youth with cerebral palsy in their transition to adult life. |
| Rutkowski S, Gerber NU, von Hoff K, Gnekow A, Bode U, Graf N, Berthold F, Henze G, Wolff JE, Warmuth-Metz M, Soerensen N, Emser A, Ottensmeier H, Deinlein F, Schlegel PG, Kortmann RD, Pietsch T, Kuehl J, German Pediatric Brain Tumor Study Group |
Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy. [+] |
Neuro-oncology 2009, 11: 201 |
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| To investigate the utility of postoperative chemotherapy in delaying radiotherapy and to identify prognostic factors in early childhood medulloblastoma, we studied children younger than 3 years of age registered to the HIT-SKK'87 (Therapieprotokoll für Säuglinge und Kleinkinder mit Hirntumoren [Brain Tumor Radiotherapy for Infants and Toddlers with Medulloblastoma] 1987) trial who received systemic interval chemotherapy until craniospinal radiotherapy was applied at 3 years of age or at relapse, from 1987 to 1993. Children with postoperative residual tumor or metastatic disease received systemic induction chemotherapy prior to interval chemotherapy. Twenty-nine children were eligible for analyses (median age, 1.7 years; median follow-up, 12.6 years). In children without macroscopic metastases, rates (+/-SEM) for 10-year progression-free survival (PFS) and overall survival (OS) were 52.9% +/- 12.1% and 58.8% +/- 11.9% (complete resection), and 55.6% +/- 16.6% and 66.7% +/- 15.7% (incomplete resection), compared with 0% and 0% in children with macroscopic metastases. Survival was superior in nine children with desmoplastic or extensive nodular histology compared with 20 children with classic medulloblastoma (10-year PFS, 88.9% +/- 10.5% and 30.0% +/- 10.3%, p = 0.003; OS, 88.9% +/- 10.5% and 40.0% +/- 11.0%, p = 0.006). Eleven of 12 children with tumor progression during chemotherapy had classic medulloblastoma. After treatment, IQ scores were inferior compared with nonirradiated children from the subsequent study, HIT-SKK'92. Classic histology, metastatic disease, and male gender were independent adverse risk factors for PFS and OS in 72 children from HIT-SKK'87 and HIT-SKK'92 combined. In terms of survival, craniospinal radiotherapy was successfully delayed especially in young children with medulloblastoma of desmoplastic/extensive nodular histology, which was a strong independent favorable prognostic factor. Because of the neurocognitive deficits of survivors, the emerging concepts to avoid craniospinal radiotherapy should rely on the histological medulloblastoma subtype. |
| Rutkowski S, von Hoff K, Emser A, Zwiener I, Pietsch T, Figarella-Branger D, Giangaspero F, Ellison DW, Garre ML, Biassoni V, Grundy RG, Finlay JL, Dhall G, Raquin MA, Grill J |
Survival and prognostic factors of early childhood medulloblastoma: an international meta-analysis. [+] |
J Clin Oncol 2010, 28: 4961 |
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| PURPOSE: To assess the prognostic role of clinical parameters and histology in early childhood medulloblastoma.
PATIENTS AND METHODS: Clinical and histologic data from 270 children younger than age 5 years diagnosed with medulloblastoma between March 1987 and July 2004 and treated within prospective trials of five national study groups were centrally analyzed.
RESULTS: Two hundred sixty children with medulloblastoma and specified histologic subtype were eligible for analysis (median age, 1.89 years; median follow-up, 8.0 years). Rates for 8-year event-free survival (EFS) and overall survival (OS) were 55% and 76%, respectively, in 108 children with desmoplastic/nodular medulloblastoma (DNMB) or medulloblastoma with extensive nodularity (MBEN); 27% and 42%, respectively, in 145 children with classic medulloblastoma (CMB); and 14% and 14%, respectively, in seven children with large-cell/anaplastic (LC/A) medulloblastoma (P < .001). Histology (DNMB/MBEN: hazard ratio [HR], 0.44; 95% CI, 0.31 to 0.64; LC/A medulloblastoma: HR, 2.27; 95% CI, 0.95 to 5.54; P < .001 compared with CMB), incomplete resection and metastases (M0R1: HR, 1.86; 95% CI, 1.29 to 2.80; M+: HR, 2.28; 95% CI, 1.50 to 3.46; P < .001 compared with M0R0), and national group were independent prognostic factors for EFS, and OS. The HRs for OS ranged from 0.14 for localized M0 and DNMB/MBEN to 13.67 for metastatic LC/A medulloblastoma in different national groups.
CONCLUSION: Our results confirm the high frequency of desmoplastic variants of medulloblastomas in early childhood and histopathology as a strong independent prognostic factor. A controlled de-escalation of treatment may be appropriate for young children with DNMB and MBEN in future clinical trials |
| Rutkowski S, Cohen B, Finlay J, Luksch R, Ridola V, Valteau-Couanet D, Hara J, Garre ML, Grill J |
Medulloblastoma in young children. [+] |
Pediatr Blood Cancer 2010, 54: 635 |
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| In early childhood medulloblastoma, three distinct treatment strategies are currently used by different national groups to improve survival rates and to delay or avoid craniospinal radiotherapy: (1) systemic chemotherapy and high-dose chemotherapy, followed by radiotherapy at relapse; (2) systemic and intraventricular chemotherapy; (3) systemic chemotherapy and local conformal radiotherapy. A role for high-dose chemotherapy to delay or avoid craniospinal radiotherapy as a part of multimodal treatment strategies, especially in young children with metastatic or postoperative residual disease, has been recognized by different co-operative groups. Clinical and histological factors such as nodular-desmoplastic variants are considered as important prognostic factors for risk-adapted treatment recommendations. |
| Rutkowski S |
Medulloblastom im Kindes- und Jugendalter. Leitlinie der Gesellschaft für Pädiatrische Onkologie und Hämatologie. |
AWMF online 2012 |
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