| 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. |
| Radtke S, Zolk O, Renner B, Paulides M, Zimmermann M, Möricke A, Stanulla M, Schrappe M, Langer T |
Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity and outcome in childhood acute lymphoblastic leukemia. |
Blood 2013, Epub ahead of print |
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| The purpose of this study was to investigate the pharmacogenetics of methotrexate (MTX) in a large cohort of pediatric patients with acute lymphoblastic leukemia (ALL) using a candidate gene approach. Therefore, 499 children with ALL from the ALL-BFM 2000 trial, who received 1996 courses of MTX at 5 g/m(2), were genotyped for 8 single nucleotide polymorphisms (SNPs) in 5 candidate genes of the MTX/folate pathway. Patients' MTX pharmacokinetics, MTX toxicity, and outcome were correlated with the genotypes. The interindividual variability in MTX kinetics had a substantial genetic component between 68% and 75%. The SLCO1B1 rs4149056 variant was significantly associated with MTX kinetics. In a multiple regression model, MTX AUC0-48h increased by 26% (P=6.8x10(-8)) per SLCO1B1 rs4149056 C allele. MTX AUC0-48h was a significant predictor of overall toxic adverse events during MTX courses (R(2)=0.043, P=2.9x10(-5)), whereas the TYMS rs34743033 tandem repeat polymorphism was predictive of stomatitis (R(2)=0.018, P=0.009), a frequent side effect of high-dose MTX. Multiple Cox regression analysis revealed an association of minimal residual disease (hazard ratio 7.3; P=3.2x10(-4)) and MTHFR rs1801131 (hazard ratio 3.1; P=0.015) with event-free survival in the ALL-BFM 2000 study population. Genetic variations substantially influence the kinetics and response to high-dose MTX therapy in childhood ALL. (ClinicalTrials.gov: NCT00430118). |
| Raetz EA, Rebora P, Conter V, Schrappe M, Devidas M, Escherich G, Imai C, De Moerloose B, Schmiegelow K, Burns MA, Elitzur S, Pieters R, Attarbaschi A, Yeoh A, Pui CH, Stary J, Cario G, Bodmer N, Moorman AV, Buldini B, Vora A, Valsecchi MG |
Outcome for Children and Young Adults With T-Cell ALL and Induction Failure in Contemporary Trials. |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2023, 41: 5025 |
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| Historically, patients with T-cell acute lymphoblastic leukemia (T-ALL) who fail to achieve remission at the end of induction (EOI) have had poor long-term survival. The goal of this study was to examine the efficacy of contemporary therapy, including allogeneic hematopoietic stem cell transplantation (HSCT) in first remission (CR1). |
| 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. |
| Ramaswamy V, Hielscher T, Mack SC, Lassaletta A, Lin T, Pajtler KW, Jones DT, Luu B, Cavalli FM, Aldape K, Remke M, Mynarek M, Rutkowski S, Gururangan S, McLendon RE, Lipp ES, Dunham C, Hukin J, Eisenstat DD, Fulton D, van Landeghem FK, Santi M, van Veelen ML, Van Meir EG, Osuka S, Fan X, Muraszko KM, Tirapelli DP, Oba-Shinjo SM, Marie SK, Carlotti CG, Lee JY, Rao AA, Giannini C, Faria CC, Nunes S, Mora J, Hamilton RL, Hauser P, Jabado N, Petrecca K, Jung S, Massimi L, Zollo M, Cinalli G, Bognár L, Klekner A, Hortobágyi T, Leary S, Ermoian RP, Olson JM, Leonard JR, Gardner C, Grajkowska WA, Chambless LB, Cain J, Eberhart CG, Ahsan S, Massimino M, Giangaspero F, Buttarelli FR, Packer RJ, Emery L, Yong WH, Soto H, Liau LM, Everson R, Grossbach A, Shalaby T, Grotzer M, Karajannis MA, Zagzag D, Wheeler H, von Hoff K, Alonso MM, Tuñon T, Schüller U, Zitterbart K, Sterba J, Chan JA, Guzman M, Elbabaa SK, Colman H, Dhall G, Fisher PG, Fouladi M, Gajjar A, Goldman S, Hwang E, Kool M, Ladha H, Vera-Bolanos E, Wani K, Lieberman F, Mikkelsen T, Omuro AM, Pollack IF, Prados M, Robins HI, Soffietti R, Wu J, Metellus P, Tabori U, Bartels U, Bouffet E, Hawkins CE, Rutka JT, Dirks P, Pfister SM, Merchant TE, Gilbert MR, Armstrong TS, Korshunov A, Ellison DW, Taylor MD |
Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis. |
Journal of clinical oncology 2016 Jul 20; 34: 2468 |
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| 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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| Ranft A, Seidel C, Hoffmann C, Paulussen M, Warby AC, van den Berg H, Ladenstein R, Rossig C, Dirksen U, Rosenbaum D, Jürgens H |
Quality of Survivorship in a Rare Disease: Clinicofunctional Outcome and Physical Activity in an Observational Cohort Study of 618 Long-Term Survivors of Ewing Sarcoma. |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2017 May 20; 35: 1704 |
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| Purpose Significantly improved survival rates in patients with Ewing sarcoma have raised interest in accessing the quality of long-term survivorship. In this study, subjective and objective measurement tools, preclassified as physical or mental scores, were used to assess clinicofunctional outcome and physical activity after intensive bone tumor treatment. Methods Long-term outcome of 618 survivors from consecutive Ewing sarcoma trials was assessed by the Toronto Extremity Salvage Score, Short-Form Health Survey (SF-36), Brief Symptom Inventory (BSI), and Rosenberg Self-Esteem Scale questionnaires and by the accelerometric StepWatch 3 Activity Monitor. Prospective measurements were correlated retrospectively with standardized primary trial data. Results were compared with 316 nonrandom healthy peers by using effect sizes ( d). Median observation time was 12.9 years from primary diagnosis (range, 3.7 to 31.2 years). Results Absolute subjective scores were moderate to good for survivors. Compared with control subjects, unfavorable outcome was shown on physical Toronto Extremity Salvage Score, SF-36 Physical Component Summary, and BSI-Somatization scales (| d| âÂÂ¥ 0.50; P < .01), in contrast to SF-36 Mental Component Summary, BSI-Anxiety, BSI-Depression, and Rosenberg Self-Esteem Scale mental scales (| d| ⤠0.31). Survivors were less active than control subjects, as demonstrated by a step count difference of 1,742 steps per day ( d = -0.43; P < .01); however, on average, the recommended level for an active lifestyle was achieved (âÂÂ¥ 10,000 steps). Location of pelvic tumor was the major inferior disease-specific prognostic factor in physical scores ( P < .01), whereas nondisease-specific inferior factors in questionnaires were older age and female sex ( P < .01). Conclusion Survivors of Ewing sarcoma apparently returned to a normal life with minor limitations. Observed reductions in physical scores should be a focus in future research to optimize treatment strategies to reduce a negative impact on the quality of survivorship. |
| Rasper M, Jabar S, Ranft A, Jürgens H, Amler S, Dirksen U |
The value of high-dose chemotherapy in patients with first relapsed Ewing sarcoma. |
Pediatric blood & cancer 2014, 61: 1382 |
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| Prognosis of patients with relapsed Ewing sarcoma (ES) is poor. The 5-year overall survival (OS) is 13%. We analyzed high-dose chemotherapy (HDtx) versus conventional chemotherapy (CHtx) in patients with relapsed ES. |
| Rasche M, von Neuhoff C, Dworzak M, Bourquin JP, Bradtke J, Göhring G, Escherich G, Fleischhack G, Graf N, Gruhn B, Haas OA, Klingebiel T, Kremens B, Lehrnbecher T, von Stackelberg A, Tchinda J, Zemanova Z, Thiede C, von Neuhoff N, Zimmermann M, Creutzig U, Reinhardt D |
Genotype-outcome correlations in pediatric AML: the impact of a monosomal karyotype in trial AML-BFM 2004. |
Leukemia 2017, 31: 2807 |
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| Rasche M, Zimmermann M, Borschel L, Bourquin JP, Dworzak M, Klingebiel T, Lehrnbecher T, Creutzig U, Klusmann JH, Reinhardt D |
Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012. |
Leukemia 2018, 32: 2167 |
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| Rasche M, Zimmermann M, Steidel E, Alonzo T, Aplenc R, Bourquin JP, Boztug H, Cooper T, Gamis AS, Gerbing RB, Janotova I, Klusmann JH, Lehrnbecher T, Mühlegger N, Neuhoff NV, Niktoreh N, Sramkova L, Stary J, Waack K, Walter C, Creutzig U, Dworzak M, Kaspers G, Kolb EA, Reinhardt D |
Survival Following Relapse in Children with Acute Myeloid Leukemia: A Report from AML-BFM and COG. |
Cancers 2021 May 12; 13 |
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| Post-relapse therapy remains critical for survival in children with acute myeloid leukemia (AML). We evaluated survival, response and prognostic variables following relapse in independent cooperative group studies conducted by COG and the population-based AML-BFM study group. BFM included 197 patients who relapsed after closure of the last I-BFM relapse trial until 2017, while COG included 852 patients who relapsed on the last Phase 3 trials (AAML0531, AAML1031). Overall survival at 5 years (OS) was 42 ± 4% (BFM) and 35 ± 2% (COG). Initial high-risk features (BFM 32 ± 6%, COG 26 ± 4%) and short time to relapse (BFM 29 ± 4%, COG 25 ± 2%) predicted diminished survival. In the BFM dataset, there was no difference in OS for patients who had a complete remission with full hematopoietic recovery (CR) following post-relapse re-induction compared to those with partial neutrophil and platelet recovery (CRp and CRi) only (52 ± 7% vs. 63 ± 10%, = 0.39). Among 90 patients alive at last follow-up, 87 had received a post-relapse hematopoietic stem cell transplant (HSCT). OS for patients with post-relapse HSCT was 54 ± 4%. In conclusion, initial high-risk features and early relapse remain prognostic. Response assessment with full hematopoietic recovery following initial relapse therapy does not predict survival. These data indicate the need for post-relapse risk stratification in future studies of relapse therapies. |
| 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. |
| Ratei R, Schabath R, Karawajew L, Zimmermann M, Möricke A, Schrappe M, Ludwig WD |
Lineage Classification of Childhood Acute Lymphoblastic Leukemia according to the EGIL Recommendations: Results of the ALL-BFM 2000 Trial. |
Klinische Padiatrie 2013, 225(S 01):S8 |
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| Flow cytometry immunophenotyping (FCM) is an undispensable tool for the diagnosis and for the treatment stratification of childhood acute lymphoblastic leukemia. The correlation of the EGIL-classification with prognostically relevant parameters like age, prednisone response and risk group is analyzed.Between March 2000 and June 2009 12 patients less than 1 year of age, 1 836 patients with 1 to less than 6 years, 620 patients with 6 to less than 10 years, 615 patients with 10 to less than 15 years and 275 patients with 15 to less than 19 years were analyzed with a comprehensive 4-color antibody panel and classified according to the EGIL recommendations.Bone marrow or peripheral blood mononuclear cells were isolated by ficoll gradient centrifugation, washed and stained with fluorochrome-conjugated antigen-specific monoclonal antibodies. Cell preparations were acquired and analyzed on a flow cytometer.Centralized FCM was performed for 2 775 patients (82.6%) with B-cell precursor acute lymphoblastic leukemia, 493 patients (14.7%) with T-cell acute lymphoblastic leukemia and 90 patients (2,7%) with biphenotypic acute leukemia. There was a slight overall predominance of male (56.1%) over female (43.9%) patients. Patients with B-cell precursor ALL had a slightly more favourable outcome with a 10y pEFS of 78±1.0%, compared to patients with a T-ALL or BAL (biphenotypic acute leukemia) phenotype with a 10y pEFS of 74±1.8% (n.s.) or 69±9.0% (p<0.009), respectively.FCM according to the EGIL recommendations not only provides diagnostic lineage determination and subclassification but also enables an initial prognostic orientation before MRD (minimal residual disease)-based risk stratification becomes available. |
| Rating P, Bornfeld N, Schlüter S, Westekemper H, Kiefer T, Stuschke M, Göricke S, Ketteler P, Ting S, Metz KA, Bechrakis NE, Biewald E |
Long-Term Results after Intraocular Surgery in Treated Retinoblastoma Eyes. |
Ocular oncology and pathology 2022, 8: 161 |
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| The aim of the study was to analyze the results of intraocular surgery in treated retinoblastoma eyes and to assess the long-term results with a priority on local recurrences, secondary enucleation, and metastases. Retrospective noncomparative case series. From March 1964 to January 2020, 42 eyes of 40 retinoblastoma patients underwent intraocular surgery. Time interval between the last therapy and surgery was 9.5 years (mean: 114 months; median: 54.5 months). 31 eyes were treated for radiogenic cataract formation with a gain in visual acuity of 61.3%. One child developed an upper eyelid metastasis, 3 showed second primary malignancies (SPM), one a late recurrence, and 2 eyes were enucleated. Retinal surgery was performed in 17 eyes; 6 eyes were done as a combined procedure. Indications were radiogenic complications in the sense of a vitreous hemorrhage in 11 eyes and a rhegmatogenous retinal detachment in 6 eyes. 41.2% of the treated eyes had a postoperative gain in visual acuity, whereas 9.5% of the eyes could not be preserved in the long term. Regarding systemic involvement 2 patients developed late recurrences and one a SPM. Surgical therapy in treated retinoblastoma is necessary in isolated cases. In our series, cataract surgery was a safe procedure with a good option of a significant increase in visual acuity. As expected, vitreoretinal treated eyes showed a limited gain in visual acuity, a higher risk of late recurrences, and a lower globe retention rate. Therefore, a careful indication and individual risk-benefit analysis are mandatory. |
| 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, Duley JA, Marinaki AM |
Pyrimidine 5' nucleotidase deficiency. |
British journal of haematology 2003, 120: 375 |
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| 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. |
| Regel I, Eichenmüller M, Mahajan UM, Hagl B, Benitz S, Häberle B, Vokuhl C, von Schweinitz D, Kappler R |
Downregulation of SFRP1 is a protumorigenic event in hepatoblastoma and correlates with beta-catenin mutations. |
Journal of cancer research and clinical oncology 2020, 146: 1153 |
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| Hepatoblastoma (HB) and pediatric hepatocellular carcinoma (HCC) are the most common malignant liver tumors in childhood. Both tumor types exhibit genetic and epigenetic alterations in the WNT/β-catenin signaling pathway, which is a key regulator of liver progenitor cells in embryonic development. The tumors demonstrate a high rate of β-catenin mutations and gene expression changes of several WNT antagonists. However, the role of the WNT inhibitory factor secreted frizzled-related protein 1 (SFRP1) has not been addressed in pediatric liver cancer so far. |
| 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 |
|
| Reinhardt D, Pekrun A, Lakomek M, Ritter J, Creutzig U |
Isolierte Myelosarkome der Haut im Kindesalter. |
Monatsschrift Kinderheilkunde 1999, 147: 346 |
|
| Reinhardt D, Pekrun A, Lakomek M, Ritter J, Creutzig U |
Primary isolated myeolosarcoma in childhood. |
Klin Pädiatr 1999, 211: 245 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| Reinhardt D, Creutzig U |
Isolated myelosarcoma in children--update and review. |
Leuk Lymphoma 2002, 43: 565 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| Reinhardt D, Thiele C, Creutzig U |
Neuropsychological sequelae in children with AML treated with or without prophylactic CNS-irradiation. |
Klin Pädiatr 2002, 214: 22 |
|
| Background: In study AML-BFM 87 the relapse rate was lower in patients receiving cranial irradiation (CRT). However, CRT has always been associated with adverse cognitive side effects. Therefore, the impact of CRT on neuropsychological function in children with AML was retrospectively evaluated.
Patients: We tested 53 children (30 boys, 23 girls) treated according to the AML-BFM-87 protocol (median age at diagnosis: 8.5 years, range 0.3 - 17.5; median time since diagnosis: 5.7 yrs, 3.8 - 10.7 yrs). To avoid any bias from additional therapy elements, patients with relapse or initial CNS involvement and transplanted patients were excluded (n=32). Our cohort was representative of the total group of 104 long term survivors of study AML-BFM 87. CNS prophylaxis consisted of ARA-C i.th., high dose ARA-C i. v. and either no CRT (n=15) or CRT (n=38) at a dose of 12 - 18 Gy depending on age.
Methods: Neuropsychological function was evaluated by psychological tests of attention and concentration (test d2 by Brickenkamp) and an intelligence test (Progressive Matrices by Raven). In addition, patients and their parents were interviewed about the occurrence of learning problems, subjective deficits in concentration and physical impairment.
Results: In the total group, no significant differences were seen between irradiated and non-irradiated patients regarding the psychological tests. However, the irradiated patients scored below the non-irradiated control group in test "d2" (concentration: 41st vs. 59th percentile). In the interview, irradiated patients tended to report more learning problems (lp) (10/36 vs. 1/14; p=0.15) and subjective deficits in concentration (con). In irradiated girls (con: 6/15 vs. 0/8; p=0.06; lp: 5/15 vs. 0/8; p=0.12) and younger patients (0 - 5 years at diagnosis; con: 7/12 vs. 2/9; p=0.18; lp 3/10 vs. 1/9; p=0.18) this trend was even more pronounced.
Conclusion: Children with AML and CRT had no significant intellectual impairment in standardized tests when compared to non-irradiated patients. However, more irradiated patients reported learning problems and subjective concentration deficits. |
| 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. |
|
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| Reinhardt D, Kurzknabe E, Löffler H, Creutzig U |
Akute Leukämien im Kindesalter mit besonderer Berücksichtigung der morphologischen Diagnostik. |
pädiatrische praxis 2004, 64: 395 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| Reiter A |
Non-Hodgkin-Lymphome im Kindesalter. |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie 2006 |
|
| 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 |
|
| 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 |
|
| Reiss UM, Bensimhon P, Zimmerman SA, Ware RE |
Hydroxyurea therapy for management of secondary erythrocytosis in cyanotic congenital heart disease. |
American journal of hematology 2007, 82: 740 |
|
| Secondary erythrocytosis in cyanotic congenital heart disease (CCHD) causes substantial morbidity because of complications of hyperviscosity, including stroke and chronic end organ damage. Phlebotomy provides temporary improvement but leads to iron deficiency and can actually increase blood viscosity. We describe the successful use of hydroxyurea (hydroxycarbamide) in four patients with uncorrected CCHD and symptomatic secondary erythrocytosis. In all patients, hydroxyurea improved symptoms of hyperviscosity. Substantial decreases in the red blood cell (RBC) count were observed, along with increases in the mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), leading to only modest declines in the circulating hemoglobin concentration. Two patients experienced transient mild myelosuppression, which promptly resolved with dose reduction of hydroxyurea. Hydroyxurea provides a novel and useful therapeutic approach to reduce hyperviscosity from secondary erythrocytosis in patients with CCHD, while preserving oxygen carrying capacity and avoiding iron depletion by phlebotomy. |
| 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 |
|
| 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 |
|
| 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 |
|
| 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. |
| 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, 224: 372 |
|
| 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. |
| Reiter A |
Non-Hodgkin Lymphoma in Children and Adolescents. |
Klinische Padiatrie 2013, 225(S 01):S87-S93 |
|
| Until the 1970s, childhood non-Hodgkin lymphoma (NHL) was an almost incurable disease. Since then tremendous progress has been made. In this article the contributions of the Berlin-Frankfurt-Münster (BFM)-group clinical studies to the development of efficacious treatment for childhood and adolescent NHL will be described.From 1975 to 2001, 6 consecutive cooperative multicenter studies were conducted into which a total of 2 190 protocol patients were enrolled. The probability of event-free survival (pEFS) at 5 years was 60% in the first study and increased to 84% in study NHL-BFM 95 while the overall survival probability increased from 65 to 89%. Landmarks in the development were the recognitions that childhood NHL is a heterogeneous disease and different biological subtypes require specifically adapted treatment strategies, that within subtypes the required treatment intensity varies significantly and that the appropriate prognostic parameters for stratification of treatment intensity differ between different NHL subentities. With increasing efficacy of chemotherapy local therapy modalities were almost completely abandoned. Central nervous system (CNS) irradiation for prevention of CNS relapses was, with few exceptions, replaced by CNS directed chemotherapy. The key role of methotrexate and its optimal risk adapted dose and administration schedule for treatment of mature B-cell neoplasm's could be enlightened and the first phase 2 study proving the activity of the anti-CD20 monoclonal antibody Rituximab as targeted therapy for pediatric B-NHL was successfully conducted. |
| Reismüller B, Peters C, Dworzak MN, Pötschger U, Urban C, Meister B, Schmitt K, Dieckmann K, Gadner H, Attarbaschi A, Mann G, on behalf of the Austrian ALL-BFM (Berlin-Frankfurt-Münster) Study Group |
Outcome of Children and Adolescents With a Second or Third Relapse of Acute Lymphoblastic Leukemia (ALL): A Population-based Analysis of the Austrian ALL-BFM (Berlin-Frankfurt-Münster) Study Group. |
Journal of pediatric hematology/oncology 2013, Epub ahead of print |
|
| We analyzed outcome of a population-based cohort of 74 children with second and third acute lymphoblastic leukemia (ALL) relapse and aimed to identify prognostic factors. Duration of previous remission and site of relapse appeared of prognostic relevance as patients with a second remission duration >1.5 years and isolated extramedullary relapse did better. Neither patient with a second bone marrow relapse who underwent previous allogeneic transplantation nor patients with T-cell ALL survived. Overall, 7 of 74 (9%) patients are in long-term remission. Stem cell transplantation seemed to be the only curative option for systemic relapse of B-cell precursor ALL as all 4 surviving patients with a second/third relapse involving the bone marrow received a transplant. Conclusively, patients with a second ALL relapse are ideal candidates for phase I/II trials exploring new innovative drugs. |
| Reinmuth S, Hohmann C, Rendtorff R, Balcerek M, Holzhausen S, Müller A, Henze G, Keil T, Borgmann-Staudt A |
Impact of chemotherapy and radiotherapy in childhood on fertility in adulthood: the FeCt-survey of childhood cancer survivors in Germany. |
Journal of cancer research and clinical oncology 2013, 139: 2071 |
|
| Improved treatment for childhood cancer has led to better survival rates of 83 % today. However, long-term side effects including infertility of pediatric patients receiving oncologic treatment remain unclear. We examined the association of chemotherapy and radiotherapy with infertility in survivors of pediatric cancer. |
| Reinhardt D, Antoniou E, Waack K |
Pediatric Acute Myeloid Leukemia-Past, Present, and Future. |
Journal of clinical medicine 2022, 11 |
|
| Relling MV, Rubnitz JE, Rivera GK, Boyett JM, Hancock ML, Felix CA, Kun LE, Walter AW, Evans WE, Pui CH |
High incidence of secondary brain tumours after radiotherapy and antimetabolites. |
Lancet (London, England) 1999 Jul 3; 354: 34 |
|
| 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. |
| Remke M, Hering E, Gerber NU, Kool M, Sturm D, Rickert CH, Gerß J, Schulz S, Hielscher T, Hasselblatt M, Jeibmann A, Hans V, Ramaswamy V, Taylor MD, Pietsch T, Rutkowski S, Korshunov A, Monoranu CM, Frühwald MC |
Somatostatin receptor subtype 2 (sst2) is a potential prognostic marker and a therapeutic target in medulloblastoma. |
Child's nervous system 2013, 29: 1253 |
|
| Neuroectodermal tumors in general demonstrate high and dense expression of the somatostatin receptor subtype 2 (sst2). It controls proliferation of both normal and neoplastic cells. sst2 has thus been suggested as a therapeutic target and prognostic marker for certain malignancies. |
| Renbarger JL, McCammack KC, Rouse CE, Hall SD |
Effect of race on vincristine-associated neurotoxicity in pediatric acute lymphoblastic leukemia patients. |
Pediatric blood & cancer 2008, 50: 769 |
|
| This report examines the association between race and vincristine-associated neurotoxicity in pediatric patients with precursor B cell acute lymphoblastic leukemia (preB ALL). Given that in vitro vincristine is metabolized more efficiently by cytochrome P450 (CYP) 3A5 than by CYP3A4 and that 70% African-Americans (vs. 20% of Caucasians) express CYP3A5, one may hypothesize that African-Americans metabolize vincristine more efficiently resulting in lower vincristine exposure and associated-toxicity. |
| 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, Hohmann C, Reinmuth S, Müller A, Dittrich R, Beyer M, Wickmann L, Keil T, Henze G, Borgmann-Staudt A |
Hormone and Sperm Analyses after Chemo- and Radiotherapy in Childhood and Adolescence. |
Klinische Padiatrie 2010, 222: 145 |
|
| Since prevalence of and reasons for infertility were unclear in survivors of childhood cancer we conducted a two centre survey in 2006 and nationwide in 2008. In 2008/2009 we undertook a study entitled |
| 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 2012, 44 Suppl 1: 219 |
|
| 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. |
| Reschke M, Biewald E, Bronstein L, Brecht IB, Dittner-Moormann S, Driever F, Ebinger M, Fleischhack G, Grabow D, Geismar D, Göricke S, Guberina M, Le Guin CHD, Kiefer T, Kratz CP, Metz K, Müller B, Ryl T, Schlamann M, Schlüter S, Schönberger S, Schulte JH, Sirin S, Süsskind D, Timmermann B, Ting S, Wackernagel W, Wieland R, Zenker M, Zeschnigk M, Reinhardt D, Eggert A, Ritter-Sovinz P, Lohmann DR, Bornfeld N, Bechrakis N, Ketteler P |
Eye Tumors in Childhood as First Sign of Tumor Predisposition Syndromes: Insights from an Observational Study Conducted in Germany and Austria. |
Cancers 2021 Apr 14; 13 |
|
| Retinoblastoma and other eye tumors in childhood are rare diseases. Many eye tumors are the first signs of a genetic tumor predisposition syndrome and the affected children carry a higher risk of developing other cancers later in life. Clinical and genetic data of all children with eye tumors diagnosed between 2013-2018 in Germany and Austria were collected in a multicenter prospective observational study. In five years, 300 children were recruited into the study: 287 with retinoblastoma, 7 uveal melanoma, 3 ciliary body medulloepithelioma, 2 retinal astrocytoma, 1 meningioma of the optic nerve extending into the eye. Heritable retinoblastoma was diagnosed in 44% of children with retinoblastoma. One child with meningioma of the optic nerve extending into the eye was diagnosed with neurofibromatosis 2. No pathogenic constitutional variant in DICER1 was detected in a child with medulloepithelioma while two children did not receive genetic analysis. Because of the known association with tumor predisposition syndromes, genetic counseling should be offered to all children with eye tumors. Children with a genetic predisposition to cancer should receive a tailored surveillance including detailed history, physical examinations and, if indicated, imaging to screen for other cancer. Early detection of cancers may reduce mortality. |
| Reulen RC, Zeegers MP, Wallace WH, Frobisher C, Taylor AJ, Lancashire ER, Winter DL, Hawkins MM, British Childhood Cancer Survivor Study |
Pregnancy outcomes among adult survivors of childhood cancer in the British Childhood Cancer Survivor Study. |
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2009, 18: 2239 |
|
| We used data from the first large-scale overwhelmingly population-based study (a) to quantify the risk of adverse pregnancy outcomes in survivors of childhood cancer in relation to cancer type and treatment and (b) to assess live birth rates relative to the general population. |
| Rhodes MM, Bates DG, Andrews T, Adkins L, Thornton J, Denham JM |
Abdominal pain in children with sickle cell disease. |
Journal of clinical gastroenterology 2014, 48: 99 |
|
| The differential diagnosis of abdominal pain is broad in any child, and further complicated in children with sickle cell disease (SCD). Acute causes of abdominal pain may require emergent surgery, such as for appendicitis or obstruction caused by a bezoar. Rapid intervention is necessary and life-saving in children with SCD and acute splenic or hepatic sequestration. The majority of children with SCD presenting to the physician's office or emergency department will have subacute reasons for their abdominal pain, including but not limited to constipation, urinary tract infection, peptic ulcer disease, and cholecystitis. Vaso-occlusive pain often presents in children as abdominal pain, but is a diagnosis of exclusion. The case of a 10-year-old girl with intermittent abdominal pain is used as a starting point to review the pathophysiology, diagnosis, and treatment of the most acute and common causes of abdominal pain in children with SCD. |
| 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 |
|
| Richter-Unruh A |
Pubertas präcox - Pubertas tarda bei Mädchen. |
ÄP Gynäkologie 4_2012 |
|
| Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, ACMG Laboratory Quality Assurance Committee |
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. |
Genetics in medicine : official journal of the American College of Medical Genetics 2015, 17: 405 |
|
| Ricklefs FL, Fritzsche F, Winkler B, Meissner B, Dührsen L, Westphal M, Rutkowski S, Martens T, Schüller U |
Relapse of a group 4 medulloblastoma after 18Â years as proven by histology and DNA methylation profiling. |
Child's nervous system 2019, 35: 1029 |
|
| Recent studies on medulloblastomas (MB) suggest that a large fraction of tumors appearing as late recurrence turn out to be secondary malignancies, e.g., malignant gliomas, after thorough molecular investigation. |
| Richter J, John K, Staiger AM, Rosenwald A, Kurz K, Michgehl U, Ott G, Franzenburg S, Kohler C, Finger J, Oschlies I, Paul U, Siebert R, Spang R, Burkhardt B, Klapper W |
Epstein-Barr virus status of sporadic Burkitt lymphoma is associated with patient age and mutational features. |
British journal of haematology 2022, 196: 681 |
|
| Sporadic Burkitt lymphoma (BL) is the most frequent tumour of children and adolescents but a rare subtype of lymphomas in adults. To date most molecular data have been obtained from lymphomas arising in the young. Recently, Epstein-Barr virus (EBV) positive and negative BL in young patients was shown to differ in molecular features. In the present study, we present a large age-overarching cohort of sporadic BL (n = 162) analysed by immunohistochemistry, translocations of MYC proto-oncogene, basic helix-loop-helix transcription factor (MYC), B-cell leukaemia/lymphoma 2 (BCL2) and B-cell leukaemia/lymphoma 6 (BCL6) and by targeted sequencing. We illustrate an age-associated inter-tumoral molecular heterogeneity in this disease. Mutations affecting inhibitor of DNA binding 3, HLH protein (ID3), transcription factor 3 (TCF3) and cyclin D3 (CCND3), which are highly recurrent in paediatric BL, and expression of sex determining region Y-box transcription factor 11 (SOX11) declined with patient age at diagnosis (P = 0·0204 and P = 0·0197 respectively). In contrast, EBV was more frequently detected in adult patients (P = 0·0262). Irrespective of age, EBV-positive sporadic BL showed significantly less frequent mutations in ID3/TCF3/CCND3 (P = 0·0088) but more often mutations of G protein subunit alpha 13 (GNA13; P = 0·0368) and forkhead box O1 (FOXO1; P = 0·0044) compared to EBV-negative tumours. Our findings suggest that among sporadic BL an EBV-positive subgroup of lymphomas increases with patient age that shows distinct pathogenic features reminiscent of EBV-positive endemic BL. |
| Richter J, John K, Staiger AM, Rosenwald A, Kurz K, Michgehl U, Ott G, Franzenburg S, Kohler C, Finger J, Oschlies I, Paul U, Siebert R, Spang R, Burkhardt B, Klapper W |
Epstein-Barr virus status of sporadic Burkitt lymphoma is associated with patient age and mutational features. |
British journal of haematology 2022, 196: 681 |
|
| Sporadic Burkitt lymphoma (BL) is the most frequent tumour of children and adolescents but a rare subtype of lymphomas in adults. To date most molecular data have been obtained from lymphomas arising in the young. Recently, Epstein-Barr virus (EBV) positive and negative BL in young patients was shown to differ in molecular features. In the present study, we present a large age-overarching cohort of sporadic BL (n = 162) analysed by immunohistochemistry, translocations of MYC proto-oncogene, basic helix-loop-helix transcription factor (MYC), B-cell leukaemia/lymphoma 2 (BCL2) and B-cell leukaemia/lymphoma 6 (BCL6) and by targeted sequencing. We illustrate an age-associated inter-tumoral molecular heterogeneity in this disease. Mutations affecting inhibitor of DNA binding 3, HLH protein (ID3), transcription factor 3 (TCF3) and cyclin D3 (CCND3), which are highly recurrent in paediatric BL, and expression of sex determining region Y-box transcription factor 11 (SOX11) declined with patient age at diagnosis (P = 0·0204 and P = 0·0197 respectively). In contrast, EBV was more frequently detected in adult patients (P = 0·0262). Irrespective of age, EBV-positive sporadic BL showed significantly less frequent mutations in ID3/TCF3/CCND3 (P = 0·0088) but more often mutations of G protein subunit alpha 13 (GNA13; P = 0·0368) and forkhead box O1 (FOXO1; P = 0·0044) compared to EBV-negative tumours. Our findings suggest that among sporadic BL an EBV-positive subgroup of lymphomas increases with patient age that shows distinct pathogenic features reminiscent of EBV-positive endemic BL. |
| Riehm H, Gadner H, Welte K |
Die West-Berliner Studie zur Behandlung der akuten lymphoblastischen Leukämie des Kindes -Erfahrungsbericht nach 6 Jahren. |
Klin. Pädiat.1977 189; 89 |
|
| Riehm H, Gadner H, Langermann HJ, Odenwald E, Henze G |
The Berlin Childhood Acute lymphoblastic Leukemia Therapy Study, 1970-1976. |
Am J Pediatr Hematol Oncol 1980, 2: 299 |
|
| Riehm H, Gadner H, Henze G, Kornhuber B, Lampert F, Niethammer D, Reiter A, Schellong G |
Results and significance of six randomized trials in four consecutive ALL-BFM studies. |
Haematology and blood transfusion 1990, 33: 439 |
|
| 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 |
|
| Rigaud C, Knörr F, Brugières L, Woessmann W |
Diagnosis and management of ALK-positive anaplastic large cell lymphoma in children and adolescents. |
Best practice & research. Clinical haematology 2023, 36: 101444 |
|
| Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a CD30-positive T cell lymphoma characterized by signalling from constitutively activated ALK fusion proteins. Most children and adolescents present in advanced stages, often with extranodal disease and B symptoms. The current front-line therapy standard of six cycles polychemotherapy reaches an event-free survival of 70%. The strongest independent prognostic factors are minimal disseminated disease and early minimal residual disease. At relapse, ALK-inhibitors, Brentuximab Vedotin, Vinblastine, or second line chemotherapy are effective re-inductions. Survival at relapse exceeds 60-70% with consolidation according to the time of relapse (Vinblastine monotherapy or allogeneic hematopoietic stem cell transplantation) so that the overall survival reaches 95%. It needs to be shown whether check-point inhibitors or long-term ALK-inhibition may substitute for transplantation. The future necessitates international cooperative trials testing whether a shift of paradigm to a chemotherapy-free regimen can cure ALK-positive ALCL. |
| Río P, Navarro S, Guenechea G, Sánchez-Domínguez R, Lamana ML, Yañez R, Casado JA, Mehta PA, Pujol MR, Surrallés J, Charrier S, Galy A, Segovia JC, Díaz de Heredia C, Sevilla J, Bueren JA |
Engraftment and in vivo proliferation advantage of gene-corrected mobilized CD34(+) cells from Fanconi anemia patients. |
Blood 2017, 130: 1535 |
|
| Previous Fanconi anemia (FA) gene therapy studies have failed to demonstrate engraftment of gene-corrected hematopoietic stem and progenitor cells (HSPCs) from FA patients, either after autologous transplantation or infusion into immunodeficient mice. In this study, we demonstrate that a validated short transduction protocol of G-CSF plus plerixafor-mobilized CD34 cells from FA-A patients with a therapeutic lentiviral vector corrects the phenotype of in vitro cultured hematopoietic progenitor cells. Transplantation of transduced FA CD34 cells into immunodeficient mice resulted in reproducible engraftment of myeloid, lymphoid, and CD34 cells. Importantly, a marked increase in the proportion of phenotypically corrected, patient-derived hematopoietic cells was observed after transplantation with respect to the infused CD34 graft, indicating the proliferative advantage of corrected FA-A hematopoietic repopulating cells. Our data demonstrate for the first time that optimized protocols of hematopoietic stem cell collection from FA patients, followed by the short and clinically validated transduction of these cells with a therapeutic lentiviral vector, results in the generation of phenotypically corrected HSPCs capable of repopulating and developing proliferation advantage in immunodeficient mice. Our results suggest that clinical approaches for FA gene therapy similar to those used in this study will facilitate hematopoietic repopulation in FA patients with gene corrected HSPCs, opening new prospects for gene therapy of FA patients. |
| Ripperger T, Bielack SS, Borkhardt A, Brecht IB, Burkhardt B, Calaminus G, Debatin KM, Deubzer H, Dirksen U, Eckert C, Eggert A, Erlacher M, Fleischhack G, Frühwald MC, Gnekow A, Goehring G, Graf N, Hanenberg H, Hauer J, Hero B, Hettmer S, von Hoff K, Horstmann M, Hoyer J, Illig T, Kaatsch P, Kappler R, Kerl K, Klingebiel T, Kontny U, Kordes U, Körholz D, Koscielniak E, Kramm CM, Kuhlen M, Kulozik AE, Lamottke B, Leuschner I, Lohmann DR, Meinhardt A, Metzler M, Meyer LH, Moser O, Nathrath M, Niemeyer CM, Nustede R, Pajtler KW, Paret C, Rasche M, Reinhardt D, Rieß O, Russo A, Rutkowski S, Schlegelberger B, Schneider D, Schneppenheim R, Schrappe M, Schroeder C, von Schweinitz D, Simon T, Sparber-Sauer M, Spix C, Stanulla M, Steinemann D, Strahm B, Temming P, Thomay K, von Bueren AO, Vorwerk P, Witt O, Wlodarski M, Wössmann W, Zenker M, Zimmermann S, Pfister SM, Kratz CP |
Childhood cancer predisposition syndromes-A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology. |
American journal of medical genetics. Part A 2017, 173: 1017 |
|
| Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review summarizes the current knowledge of cancer predisposition syndromes in pediatric oncology and provides essential information on clinical situations in which a childhood cancer predisposition syndrome should be suspected. |
| 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 |
|
| Ritterbusch H, Ehl, S |
Hämophagozytose Syndrom. |
Informationsblätter Primäre Immundefekte |
|
| Ritter-Sovinz P, Temming P, Wackernagel W, Tarmann L, Langmann G, Benesch M, Lackner H, Karastaneva A, Schwinger W, Seidel M, Sperl D, Strenger V, Sorantin E, Urban C |
Retinoblastom - Klinische Symptome, Diagnostik und Management. |
Monatsschrift Kinderheilkunde 165, 764-771 2017 |
|
| Ritz A, Kolorz J, Hubertus J, Ley-Zaporozhan J, von Schweinitz D, Koletzko S, Häberle B, Schmid I, Kappler R, Berger M, Lurz E |
Sarcopenia is a prognostic outcome marker in children with high-risk hepatoblastoma. |
Pediatric blood & cancer 2021, 68:e28862 |
|
| Children with hepatoblastoma (HB) are at risk of sarcopenia due to immobility, chemotherapy, and malnutrition. We hypothesized that children with HB have a low preoperative total psoas muscle area (tPMA), reflecting sarcopenia, which negatively impacts outcome. |
| Rizzari C, Conter V, Starý J, Colombini A, Moericke A, Schrappe M |
Optimizing asparaginase therapy for acute lymphoblastic leukemia. |
Current opinion in oncology 2013, 25 Suppl 1:S1 |
|
| Asparaginases are important agents used in the treatment of children with acute lymphoblastic leukemia (ALL). Three types of asparaginase are currently available: two are derived from Escherichia coli [native asparaginase and pegylated asparaginase (PEG-asparaginase)] and one from Erwinia chrysanthemi (crisantaspase). All three products share the same mechanism of action but have different pharmacokinetic properties, which do not make them easily interchangeable. Among the known toxicities and side-effects, allergic reactions and silent inactivation represent the most important limitations to the prolonged use of any asparaginase product, with associated reduced therapeutic effects and poorer outcomes. Routine real time monitoring can help to identify patients with silent inactivation and facilitate a switch to a different product to ensure continued depletion of asparagine, completion of the treatment schedule and maintenance of outcomes. However, the most appropriate second-line treatment is still a matter of debate. PEG-asparaginase has lower immunogenicity and a longer half-life than native Escherichia coli (E. coli) asparaginase, which makes it useful for both first-line and second-line use with a reduced number of doses. However, PEG-asparaginase displays cross-reactivity with native E. coli asparaginase that may harm its therapeutic effects. Crisantaspase does not display cross-reactivity to either of the E. coli-derived products, which has made crisantaspase the second-line treatment option in a number of recent protocols. As crisantaspase has a much shorter biological half-life than the E. coli-derived products, the appropriate dosage and administration schedule are of paramount importance in delivering treatment with this product. In the ongoing trial AIEOP-BFM ALL 2009 (Associazione Italiana Ematologia Oncologia Pediatrica - Berlin-Franklin-Munster), in which PEG-asparaginase is used first-line, one dose of PEG-asparaginase is substituted by seven doses of crisantaspase given intravenously at 20,000 IU/m2 on alternate days when clinical allergy or silent inactivation is present. Based on the indications of different protocols, lack of cross-reactivity to the E. coli-derived products and taking into consideration regulatory factors and availability, crisantaspase may be considered a viable second-line therapy. |
| Rizzari C, Lanvers-Kaminsky C, Valsecchi MG, Ballerini A, Matteo C, Gerss J, Wuerthwein G, Silvestri D, Colombini A, Conter V, Biondi A, Schrappe M, Moericke A, Zimmermann M, von Stackelberg A, Linderkamp C, Frühwald MC, Legien S, Attarbaschi A, Reismüller B, Kasper D, Smisek P, Stary J, Vinti L, Barisone E, Parasole R, Micalizzi C, Zucchetti M, Boos J |
Asparagine levels in the cerebrospinal fluid of children with acute lymphoblastic leukemia treated with pegylated-asparaginase in the induction phase of the AIEOP-BFM ALL 2009 study. |
Haematologica 2019, 104: 1812 |
|
| Asparagine levels in cerebrospinal fluid and serum asparaginase activity were monitored in children with acute lymphoblastic leukemia treated with pegylated-asparaginase. The drug was given intravenously at a dose of 2,500 IU/m on days 12 and 26. Serum and cerebrospinal fluid samples obtained on days 33 and 45 were analyzed centrally. Since physiological levels of asparagine in the cerebrospinal fluid of children and adolescents are 4-10 µmol/L, in this study asparagine depletion was considered complete when the concentration of asparagine was <=0.2 µmol/L, i.e. below the lower limit of quantification of the assay used. Over 24 months 736 patients (AIEOP n=245, BFM n=491) and 903 cerebrospinal fluid samples (n=686 on day 33 and n=217 on day 45) were available for analysis. Data were analyzed separately for the AIEOP and BFM cohorts and yielded superimposable results. Independently of serum asparaginase activity levels, cerebrospinal fluid asparagine levels were significantly reduced during the investigated study phase but only 28% of analyzed samples showed complete asparagine depletion while relevant levels, >1 µmol/L, were still detectable in around 23% of them. Complete cerebrospinal fluid asparagine depletion was found in around 5-6% and 33-37% of samples at serum asparaginase activity levels <100 and >0 1,500 IU/L, respectively. In this study cerebrospinal fluid asparagine levels were reduced during pegylated-asparaginase treatment, but complete depletion was only observed in a minority of patients. No clear threshold of serum pegylated-asparaginase activity level resulting in complete cerebrospinal fluid asparagine depletion was identified. The consistency of the results found in the two independent data sets strengthen the observations of this study. Details of the treatment are available in the European Clinical Trials Database at . |
| Rizzari C, Möricke A, Valsecchi MG, Conter V, Zimmermann M, Silvestri D, Attarbaschi A, Niggli F, Barbaric D, Stary J, Elitzur S, Cario G, Vinti L, Boos J, Zucchetti M, Lanvers-Kaminsky C, von Stackelberg A, Biondi A, Schrappe M |
Incidence and Characteristics of Hypersensitivity Reactions to PEG-asparaginase Observed in 6136 Children With Acute Lymphoblastic Leukemia Enrolled in the AIEOP-BFM ALL 2009 Study Protocol. |
HemaSphere 2023, 7:e893 |
|
| The incidence of hypersensitivity reactions (HSRs) to PEG-asparaginase (PEG-ASNase) was evaluated in 6136 children with ALL enrolled in the AIEOP-BFM ALL 2009 study. Patients with B-cell precursor-acute lymphoblastic leukemia (BCP-ALL) were stratified as standard-risk/medium-risk (MR)/high-risk (HR) and those with T-ALL as non-High/HR. PEG-ASNase was administered intravenously at 2500 IU/sqm/dose. All patients received 2 PEG-ASNase doses in induction; thereafter non-HR versus HR patients received 1 versus 6 PEG-ASNase doses, respectively. After the single regular dose of PEG-ASNase at the beginning of delayed intensification, BCP-ALL-MR patients were randomized to receive 9 additional PEG-ASNase doses every 2 weeks (experimental arm [EA]) versus none (standard arm [SA]); HR patients were randomized to receive, in consolidation, 4 weekly PEG-ASNase doses (EA) versus none (SA). The HSR cumulative incidence (CI) was estimated adjusting for competing risks. An HSR occurred in 472 of 6136 (7.7%) patients. T-non- HR/BCP-Standard-Risk, BCP-MR-SA, BCP-MR-EA, HR-SA and HR-EA patients had 1-year-CI-HSR (±SE) rates of 5.2% (0.5), 5.2% (0.5), 4.0% (0.8), 20.2% (1.2), and 6.4% (1.3), respectively. The randomized intensification of PEG-ASNase did not significantly impact on HSR incidence in BCP-MR patients (1-y-CI-HSR 3.8% [0.8] versus 3.2% [0.6] in MR-EA versus MR-SA; = 0.55), while impacted significantly in HR patients (1-y-CI-HSR 6.4% [1.3] versus 17.9% [1.8] in HR-EA and HR-SA, respectively; < 0.001). The CI-HSR was comparable among non-HR groups and was not increased by a substantial intensification of PEG-ASNase in the BCP-MR-EA group whilst it was markedly higher in HR-SA than in HR-EA patients, suggesting that, in such a chemotherapy context, a continuous exposure to PEG-ASNase reduces the risk of developing an HSR. |
| 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 |
|
| Robertson PL, Muraszko KM, Holmes EJ, Sposto R, Packer RJ, Gajjar A, Dias MS, Allen JC, Children's Oncology Group |
Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: a prospective study by the Children's Oncology Group. |
Journal of neurosurgery 2006, 105(6 Suppl): 444 |
|
| Cerebellar mutism syndrome (CMS) is a unique postoperative syndrome typically arising 1 to 2 days after resection of a midline posterior fossa tumor; it consists of diminished speech progressing to mutism, emotional lability, hypotonia, and ataxia. Most descriptions have been limited to small institutional series using a retrospective chart review methodology. |
| Robinson TM, Fuchs EJ |
Allogeneic stem cell transplantation for sickle cell disease. |
Current opinion in hematology 2016, 23: 524 |
|
| 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. |
| Do BK, Rodger DC |
Sickle cell disease and the eye. |
Current opinion in ophthalmology 2017, 28: 623 |
|
| PURPOSE OF REVIEW:
To review recent literature pertaining to sickle cell retinopathy (SCR) and, in particular, sickle cell maculopathy.
RECENT FINDINGS:
Several recent studies suggest that macular perfusion abnormalities seen in patients with sickle cell disease of various genotypes may affect both the superficial and deep capillary plexi, with a predilection for the deep capillary plexus. Further, these changes may be associated with areas of macular thinning, as well as with peripheral retinal ischemia, even in individuals without visual symptoms, contrary to what has previously been described in both diabetic retinopathy and retinal vein occlusion. Several cases also suggest that paracentral acute middle maculopathy may be the pathophysiologic mechanism by which microvascular occlusion leads to macular thinning.
SUMMARY:
Sickle cell disease can manifest in a number of ways within the orbit as well as intraocularly because of its nonspecific vasoocclusive episodes. However, SCR is the most common ophthalmic manifestation of this disease. Historically, SCR has been considered a peripheral retinopathy, but the development and use of spectral-domain optical coherence tomography and optical coherence tomography angiography suggest that significant macular vascular changes occur early in this disease, even in asymptomatic individuals. |
| Rodriguez-Fos E, Planas-Fèlix M, Burkert M, Puiggròs M, Toedling J, Thiessen N, Blanc E, Szymansky A, Hertwig F, Ishaque N, Beule D, Torrents D, Eggert A, Koche RP, Schwarz RF, Haase K, Schulte JH, Henssen AG |
Mutational topography reflects clinical neuroblastoma heterogeneity. |
Cell genomics 2023, 3: 100402 |
|
| Neuroblastoma is a pediatric solid tumor characterized by strong clinical heterogeneity. Although clinical risk-defining genomic alterations exist in neuroblastomas, the mutational processes involved in their generation remain largely unclear. By examining the topography and mutational signatures derived from all variant classes, we identified co-occurring mutational footprints, which we termed mutational scenarios. We demonstrate that clinical neuroblastoma heterogeneity is associated with differences in the mutational processes driving these scenarios, linking risk-defining pathognomonic variants to distinct molecular processes. Whereas high-risk -amplified neuroblastomas were characterized by signs of replication slippage and stress, homologous recombination-associated signatures defined high-risk non--amplified patients. Non-high-risk neuroblastomas were marked by footprints of chromosome mis-segregation and TOP1 mutational activity. Furthermore, analysis of subclonal mutations uncovered differential activity of these processes through neuroblastoma evolution. Thus, clinical heterogeneity of neuroblastoma patients can be linked to differences in the mutational processes that are active in their tumors. |
| Roessner A, Jürgens H |
Round cell tumours of bone. |
Pathol Res Pract 1993, 189: 111 |
|
| Rossig C, Jürgens H, Schrappe M, Moericke A, Henze G, von Stackelberg A, Reinhardt D, Burkhardt B, Woessmann W, Zimmermann M, Gadner H, Mann G, Schellong G, Mauz-Koerholz C, Dirksen U, Bielack S, Berthold F, Graf N, Rutkowski S, Calaminus G, Kaatsch P, Creutzig U |
Effective childhood cancer treatment: the impact of large scale clinical trials in Germany and Austria. |
Pediatric blood & cancer 2013, 60: 1574 |
|
| Rösler P, Christiansen H, Kortmann RD, Martini C, Matuschek C, Meyer F, Rübe C, Langer T, Koch R, Eich HT, Willich N, Steinmann D |
Hepatotoxicity after liver irradiation in children and adolescents : Results from the RiSK. |
Strahlentherapie und Onkologie 2015, 191: 413 |
|
| The aim of this study was to evaluate acute and late radiotherapy-associated hepatotoxicity in consideration of dose-volume effects and liver function in childhood and adolescence. |
| Römer T, Franzen S, Kravets H, Farrag A, Makowska A, Christiansen H, Eble MJ, Timmermann B, Staatz G, Mottaghy FM, Bührlen M, Hagenah U, Puzik A, Driever PH, Greiner J, Jorch N, Tippelt S, Schneider DT, Kropshofer G, Overbeck TR, Christiansen H, Brozou T, Escherich G, Becker M, Friesenbichler W, Feuchtinger T, Puppe W, Heussen N, Hilgers RD, Kontny U |
Multimodal Treatment of Nasopharyngeal Carcinoma in Children, Adolescents and Young Adults-Extended Follow-Up of the NPC-2003-GPOH Study Cohort and Patients of the Interim Cohort. |
Cancers 2022, 14 |
|
| Nasopharyngeal carcinoma (NPC) in children and young adults has been treated within two consecutive prospective trials in Germany, the NPC-91 and the NPC-2003 study of the German Society of Pediatric Oncology and Hematology (GPOH). In these studies, multimodal treatment with induction chemotherapy, followed by radio (chemo)therapy and interferon-beta maintenance, yielded promising survival rates even after adapting total radiation doses to tumor response. The outcome of 45 patients in the NPC-2003 study was reassessed after a median follow-up of 85 months. In addition, we analyzed 21 further patients after closure of the NPC-2003 study, recruited between 2011 and 2017, and treated as per the NPC-2003 study protocol. The EFS and OS of 66 patients with locoregionally advanced NPC were 93.6% and 96.7%, respectively, after a median follow-up of 73 months. Seven patients with CR after induction therapy received a reduced radiation dose of 54 Gy; none relapsed. In young patients with advanced locoregional NPC, excellent long-term survival rates can be achieved by multimodal treatment, including interferon-beta. Radiation doses may be reduced in patients with complete remission after induction chemotherapy and may limit radiogenic late effects. |
| Rogge T, Niemeyer C |
Myelodysplastic syndromes in childhood. |
Onkologie 2000, 23: 18 |
|
| Rogers TN, Seitz G, Fuchs J, Martelli H, Dasgupta R, Routh JC, Hawkins DS, Koscielniak E, Bisogno G, Rodeberg DA |
Surgical management of paratesticular rhabdomyosarcoma: A consensus opinion from the Children's Oncology Group, European paediatric Soft tissue sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe. |
Pediatric blood & cancer 2021, 68:e28938 |
|
| The treatment of paratesticular rhabdomyosarcoma (PT-RMS) has varied over time and by cooperative group. The International Soft Tissue Sarcoma Database Consortium (INSTRuCT) is a collaboration of the Children's Oncology Group (COG) Soft Tissue Sarcoma Committee, European pediatric Soft tissue sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS). The INSTRuCT surgical committee has been given charge of the development of internationally applicable consensus guidelines for the surgical treatment of rhabdomyosarcoma. This clinical consensus opinion document addresses accepted principles and areas of controversy, such as scrotal violation and retroperitoneal nodal evaluation, providing an evidence-based guideline for the surgical treatment for PT-RMS. |
| 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 |
|
| Rohmer B, Valla FV, Baleydier F, Launay V, Dommange-Romero F, Pondarré C |
Newly Diagnosed Immune Thrombocytopenic Purpura in Childhood: Successful Implementation of a Limited Intervention Strategy in the Setting of Pediatric Emergency Care. |
The Journal of pediatrics 2014, Epub ahead of print |
|
| Immune thrombocytopenic purpura is a bleeding disorder for which management remains mainly guided by platelet counts. Pediatric hematologists and emergency physicians collaborated to set up a limited intervention strategy, focusing on clinical bleeding severity irrespective of platelet counts, starting in the emergency room. We report how this strategy was safely applied for 106 consecutive children admitted for newly diagnosed immune thrombocytopenic purpura. |
| Rohde M, Bonn BR, Zimmermann M, Lange J, Möricke A, Klapper W, Oschlies I, Szczepanowski M, Nagel I, Schrappe M, MMML-MYC-SYS Project, ICGC MMML-Seq Project, Loeffler M, Siebert R, Reiter A, Burkhardt B |
Relevance of ID3-TCF3-CCND3 pathway mutations in pediatric aggressive B-cell lymphoma treated according to the non-Hodgkin Lymphoma Berlin-Frankfurt-Muenster protocols. |
Haematologica 2017, 102: 1091 |
|
| 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. |
| Rolf N, Bugert P, Gehrisch S, Siegert G, Suttorp M, Knöfler R |
[Clinical and laboratory aspects of the Aspirin-like defect as hereditary thrombocytopathy]. |
Hamostaseologie 2009, 29: 177 |
|
| The Aspirin-like defect (ALD) is caused by defects in the intraplatelet arachidonic acid (AA)-metabolism. We here present the characteristics of a larger cohort in a single centre. |
| 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 |
|
| Rombout-Sestrienkova E, Winkens B, Essers BA, Nieman FH, Noord PA, Janssen MC, van Deursen CT, Boonen A, Reuser-Kaasenbrood EP, Heeremans J, van Kraaij M, Masclee A, Koek GH |
Erythrocytapheresis versus phlebotomy in the maintenance treatment of HFE hemochromatosis patients: results from a randomized crossover trial. |
Transfusion 2016, 56: 261 |
|
| Phlebotomy is standard maintenance treatment of patients with hereditary hemochromatosis (HH). Erythrocytapheresis, which selectively removes red blood cells, provides a new, potentially more effective treatment option. Our aim was to evaluate the effectiveness of erythrocytapheresis over phlebotomy for maintenance therapy in patients with HH. |
| Ronceray L, Abla O, Barzilai-Birenboim S, Bomken S, Chiang AK, Jazbec J, Kabickova E, Lazic J, Beishuizen A, Mellgren K, Tanaka F, Pillon M, Devalck C, Gouttenoire M, Makarova O, Burkhardt B, Attarbaschi A, European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL) and the International Berlin-Frankfurt-Münster (i-BFM) Study Group |
Children and adolescents with marginal zone lymphoma have an excellent prognosis with limited chemotherapy or a watch-and-wait strategy after complete resection. |
Pediatric blood & cancer 2018, 65 |
|
| Ropero P, Arbeteta J, Nieto JM, González FA, González B, Villegas A, Benavente C |
Nondeletional alpha-Thalassemia: Two New Mutations on the alpha2 Gene. |
Hemoglobin 2020, 1 |
|
| About 10.0% of α-thalassemia (α-thal) cases are due to point mutations, small deletions, or insertions of one or more bases on the α genes that can alter mRNA processing at the transcription, translation, or post-translation level; these cases are called nondeletional α-thalassemias (α-thal). Most occur within the domain of the α2 gene without changes in the expression of the α1 gene. We present two new frameshift mutations on the HBA2 gene, associated with a nondeletional α-thal phenotype. The probands were referred to our clinic because of persistent microcytosis and hypochromia. The molecular characterization was performed by automatic sequencing of the α-globin genes. Two new mutations were detected on the HBA2 gene; HBA2: c.85delG, p.(Ala29fs*21), and HBA2: c.268_280delCACAAGCTTCGGG, p.(His90Trpfs*9). These new mutations cause a change of the reading frame, the first on codon 28 and the second from codons 89 to 93. In the first mutation, the result is an altered amino acid sequence and a premature termination codon at position 87, while the elimination of 13 bp generates a protein of 95 residues and in this case, the premature termination codon is at position 96. These types of mutation are among the most damaging changes to the coding of a protein. Not only do they lead to changes in the length of the polypeptide, but they also vary the chemical composition, which would result in a nonfunctional protein. The importance of identifying these new mutations lies in their possible association with α0-thal, which could lead to a severe thalassemia. |
| 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. |
| Rossig C, Jürgens H, Schrappe M, Moericke A, Henze G, von Stackelberg A, Reinhardt D, Burkhardt B, Woessmann W, Zimmermann M, Gadner H, Mann G, Schellong G, Mauz-Koerholz C, Dirksen U, Bielack S, Berthold F, Graf N, Rutkowski S, Calaminus G, Kaatsch P, Creutzig U |
Effective childhood cancer treatment: The impact of large scale clinical trials in Germany and Austria. |
Pediatric blood & cancer 2013, 60: 1574 |
|
| In Germany and Austria, more than 90% of pediatric cancer patients are enrolled into nationwide disease-specific first-line clinical trials or interim registries. Essential components are a pediatric cancer registry and centralized reference laboratories, imaging review, and tumor board assistance. The five-year overall survival rate in countries where such infrastructures are established has improved from <20% before 1950 to >80% since 1995. Today, treatment intensity is tailored to the individual patient's risk to provide the highest chances of survival while minimizing deleterious late effects. Multicenter clinical trials are internationalized and serve as platforms for further improvements by novel drugs and biologicals. Pediatr Blood Cancer 2013;60:1574-1581. © 2013 Wiley Periodicals, Inc. |
| Rosolen A, Perkins SL, Pinkerton CR, Guillerman RP, Sandlund JT, Patte C, Reiter A, Cairo MS |
Revised International Pediatric Non-Hodgkin Lymphoma Staging System. |
Journal of clinical oncology 2015, 33: 2112 |
|
| Treatment and prognosis of pediatric non-Hodgkin lymphoma (NHL) have improved dramatically in the last 30 years. However, the St Jude NHL staging classification for pediatric NHL was developed more than 35 years ago. The most recent Lugano lymphoma staging classification focused on adult lymphoma. Furthermore, major limitations of the current pediatric NHL staging classification include lack of consideration of new distinct pediatric NHL histologic entities; absence of recognition of frequent skin, bone, kidney, ovarian, and other organ involvement; and lack of newer precise methods to detect bone marrow and CNS involvement, minimal disease quantification, and highly sensitive imaging technologies. |
| Rosswog C, Bartenhagen C, Welte A, Kahlert Y, Hemstedt N, Lorenz W, Cartolano M, Ackermann S, Perner S, Vogel W, Altmüller J, Nürnberg P, Hertwig F, Göhring G, Lilienweiss E, Stütz AM, Korbel JO, Thomas RK, Peifer M, Fischer M |
Chromothripsis followed by circular recombination drives oncogene amplification in human cancer. |
Nature genetics 2021, 53: 1673 |
|
| Rosswog C, Fassunke J, Ernst A, Schömig-Markiefka B, Merkelbach-Bruse S, Bartenhagen C, Cartolano M, Ackermann S, Theissen J, Blattner-Johnson M, Jones B, Schramm K, Altmüller J, Nürnberg P, Ortmann M, Berthold F, Peifer M, Büttner R, Westermann F, Schulte JH, Simon T, Hero B, Fischer M |
Genomic ALK alterations in primary and relapsed neuroblastoma. |
British journal of cancer 2023, 128: 1559 |
|
| Genomic alterations of the anaplastic lymphoma kinase gene (ALK) occur recurrently in neuroblastoma, a pediatric malignancy of the sympathetic nervous system. However, information on their development over time has remained sparse. |
| 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. |
| Roy CN, Andrews NC |
Recent advances in disorders of iron metabolism: mutations, mechanisms and modifiers. |
Human molecular genetics 2001 Oct 1; 10: 2181 |
|
| 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 |
|
| Rozen WM, Joseph S, Lo PA |
Spontaneous regression of low-grade gliomas in pediatric patients without neurofibromatosis. |
Pediatric neurosurgery 2008, 44: 324 |
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| Pediatric low-grade gliomas comprise a diverse range of central nervous system tumors, sharing the usual course of a slow progression in growth. In individual cases however, the natural history can be variable, and rarely spontaneous regression has been described. This paper describes factors associated with spontaneous regression. |
| 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. |
| Rudzinski ER, Kelsey A, Vokuhl C, Linardic CM, Shipley J, Hettmer S, Koscielniak E, Hawkins DS, Bisogno G |
Pathology of childhood rhabdomyosarcoma: A consensus opinion document from the Children's Oncology Group, European Paediatric Soft Tissue Sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe. |
Pediatric blood & cancer 2021, 68:e28798 |
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| The diagnosis and classification of rhabdomyosarcoma (RMS) has undergone several shifts over the last 30 years. While the main diagnostic categories remained the same, changes in the histologic criteria necessary for diagnosis, as well as varied reliance on immunohistochemical and molecular data over time, have created confusion, particularly regarding how these shifts impacted risk stratification and enrollment onto clinical trials. The goal of this report is to review the evolution and current status of RMS diagnosis, focusing on diagnostic criteria in the Children's Oncology Group (COG), the European Paediatric Soft Tissue Sarcoma Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS). In addition, we emphasize research tools used to classify RMS and address biological questions within current clinical trials run by each group. The INternational Soft Tissue SaRcoma ConsorTium (INSTRuCT) initiative will maximize potential to optimize risk stratification by recognizing and accounting for differences in historical data and current practices. |
| Rudelius M, Weinberg OK, Niemeyer CM, Shimamura A, Calvo KR |
The International Consensus Classification (ICC) of hematologic neoplasms with germline predisposition, pediatric myelodysplastic syndrome, and juvenile myelomonocytic leukemia. |
Virchows Archiv : an international journal of pathology 2023, 482: 113 |
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| 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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| Ruether C, Wuensch C, Randau G, Michgehl U, Trautmann M, Hartmann W, Sandmann S, Dugas M, Khanam T, Burkhardt B |
Design of a targeted next-generation DNA sequencing panel for pediatric T-cell lymphoblastic lymphoma to unravel biology and optimize treatment. |
Genes, chromosomes & cancer 2022, 61: 459 |
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| Low incidence and molecular heterogeneity of pediatric T-cell lymphoblastic lymphoma (T-LBL) require an international, large-scale effort to identify novel clinical biomarkers. The ongoing international clinical trial LBL2018 (NCT04043494) represents an ideal opportunity to implement a common analytic approach. Targeted next-generation sequencing is well-suited for this purpose; however, selection of relevant target genes for T-LBL remains subject of ongoing debates. Our group has recently designed and evaluated a first target panel of 80 candidate genes for T-LBL. The present study aimed at developing a novel optimized gene panel for large-scale application and to promote an international agreement on a common core panel. Small sequence variants obtained from our former study were systematically analyzed and classified with regards to pathogenic relevance, to prioritize candidate genes. Additional genes were curated from literature and online databases for a more comprehensive analysis of relevant functions and signaling pathways. The new target panel TGP-T-LBL entails 84 candidate genes which are key actors in NOTCH, PI3K-AKT, JAK-STAT, RAS signaling, epigenetic regulation, transcription, DNA repair, cell cycle regulation, and ribosomal function. From our former gene panel, 35 out of 80 candidate genes were selected for the novel panel. Forty-six out of 84 genes are currently being analyzed in the ongoing international trial LBL2018. Exploratory analysis of prognostic relevance on mutation-level suggested a potential association of PIK3CA variants c.1624G>A(p.Glu542Lys) and c.1633G>A(p.Glu545Lys) to occurrence of relapse, emphasizing particular relevance of mutation analysis in PI3K-AKT signaling. Our approach promotes comprehensive and clinically relevant mutational profiling of pediatric T-LBL. |
| Ruf S, Brugieres L, Pillon M, Zimmermann M, Attarbaschi A, Melgrenn K, Williams D, Uyttebroeck A, Wrobel G, Reiter A, Woessmann W |
Risk-adapted therapy for patients with relapsed or refractory ALCL - final report of the prospective ALCL-Relapse Trial of the EICNHL. |
Br J Haematol 2015, 171: 45 |
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| Ruf S, Hebart H, Hjalgrim LL, Kabickova E, Lang P, Steinbach D, Schwabe GC, Woessmann W |
CNS progression during vinblastine or targeted therapies for high-risk relapsed ALK-positive anaplastic large cell lymphoma: A case series. |
Pediatric blood & cancer 2018, 65:e27003 |
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| Ruge MI, Simon T, Suchorska B, Lehrke R, Hamisch C, Koerber F, Maarouf M, Treuer H, Berthold F, Sturm V, Voges J |
Stereotactic brachytherapy with iodine-125 seeds for the treatment of inoperable low-grade gliomas in children: long-term outcome. |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2011 Nov 1; 29: 4151 |
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| Resection is generally considered the gold standard for treatment of low-grade (WHO grades I and II) gliomas (LGGs) in childhood. However, approximately 30% to 50% of these tumors are inoperable because of their localization in highly eloquent brain areas. A few reports have suggested stereotactic brachytherapy (SBT) with implantation of iodine-125 ((125)I) seeds as a safe and effective local treatment alternative. This single-center study provides a summary of the long-term outcome after SBT in one of the largest reported patient series. |
| 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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| Invasive Candida infections are important causes of morbidity and mortality in immunocompromised and hospitalised patients. This article provides the joint recommendations of the German-speaking Mycological Society (Deutschsprachige Mykologische Gesellschaft, DMyKG) and the Paul-Ehrlich-Society for Chemotherapy (PEG) for diagnosis and treatment of invasive and superficial Candida infections. The recommendations are based on published results of clinical trials, case-series and expert opinion using the evidence criteria set forth by the Infectious Diseases Society of America (IDSA). Key recommendations are summarised here: The cornerstone of diagnosis remains the detection of the organism by culture with identification of the isolate at the species level; in vitro susceptibility testing is mandatory for invasive isolates. Options for initial therapy of candidaemia and other invasive Candida infections in non-granulocytopenic patients include fluconazole or one of the three approved echinocandin compounds; liposomal amphotericin B and voriconazole are secondary alternatives because of their less favourable pharmacological properties. In granulocytopenic patients, an echinocandin or liposomal amphotericin B is recommended as initial therapy based on the fungicidal mode of action. Indwelling central venous catheters serve as a main source of infection independent of the pathogenesis of candidaemia in the individual patients and should be removed whenever feasible. Pre-existing immunosuppressive treatment, particularly by glucocorticosteroids, ought to be discontinued, if feasible, or reduced. The duration of treatment for uncomplicated candidaemia is 14 days following the first negative blood culture and resolution of all associated symptoms and findings. Ophthalmoscopy is recommended prior to the discontinuation of antifungal chemotherapy to rule out endophthalmitis or chorioretinitis. Beyond these key recommendations, this article provides detailed recommendations for specific disease entities, for antifungal treatment in paediatric patients as well as a comprehensive discussion of epidemiology, clinical presentation and emerging diagnostic options of invasive and superficial Candida infections. |
| Ruland V, Hartung S, Kordes U, Wolff JE, Paulus W, Hasselblatt M |
Choroid plexus carcinomas are characterized by complex chromosomal alterations related to patient age and prognosis. |
Genes, chromosomes & cancer 2014, 53: 373 |
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| Choroid plexus carcinoma is a malignant brain tumor predominantly occurring in young children. Only limited data are available regarding the underlying molecular genetic alterations. Therefore, molecular inversion probe single nucleotide polymorphism (MIP SNP) arrays were performed on a series of 26 neuropathologically well-characterized choroid plexus carcinomas. Recurrent copy number losses of chromosomes 5, 6, 16, 18, 19, and 22 as well as gains of chromosomes 1, 2, 4, 12, and 20 were identified. Furthermore, GISTIC analysis identified significant recurrent gains of 17 genes in 9 regions, and recurrent losses of 96 genes in 14 regions. Clustering analysis separated choroid plexus carcinomas into two groups: one characterized by marked losses and the other characterized by gains across the chromosomes. Chromosomal losses of 9, 19p, and 22q were significantly more frequent in younger children (<36 months), whereas gains on chromosomes 7 and 19, and chromosome arms 8q, 14q, and 21q prevailed in older patients. Multivariate analysis revealed that loss of 12q was associated with shorter survival [12 ± 5 months vs. 86 ± 8 months; (mean ± SD; P = 0.001)] and, in addition, 45 smaller chromosomal regions showing genetic alterations significantly associated with survival could be identified. The MIP SNP array profiles also contributed to the diagnosis of two difficult SMARCB1-negative tumors as choroid plexus carcinoma and cribriform neuroepithelial tumor (CRINET), respectively. In conclusion, choroid plexus carcinomas are characterized by complex genetic alterations, which are related to patient age and may have prognostic and diagnostic value. |
| Rund D, Rachmilewitz E |
Beta-thalassemia. |
The New England journal of medicine 2005, 353: 1135 |
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| Rustler V, Hagerty M, Daeggelmann J, Marjerrison S, Bloch W, Baumann FT |
Exercise interventions for patients with pediatric cancer during inpatient acute care: A systematic review of literature. |
Pediatric blood & cancer 2017, 64 |
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| Physical inactivity has been shown to exacerbate negative side effects experienced by pediatric patients undergoing cancer therapy. Exercise interventions are being created in response. This review summarizes current exercise intervention data in the inpatient pediatric oncology setting. Two independent reviewers collected literature from three databases, and analyzed data following the PRISMA statement for systematic reviews and meta-analyses. Ten studies were included, representing 204 patients. Good adherence, positive trends in health status, and no adverse events were noted. Common strategies included individual, supervised, combination training with adaptability to meet fluctuating patient abilities. We recommend that general physical activity programming be offered to pediatric oncology inpatients. |
| 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 2018 |
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| Rutkowski S, Pfister S, Frühwald M, Fleischhack G, Korinthenberg R, Bison B, Hahn G, Mentzel H-J, Langen K-J, Hernáiz-Driever P, Pietsch T |
Leitsymptome und Diagnostik der ZNS-Tumoren im Kindes- und Jugendalter. |
Gemeinsame Leitlinie der Gesellschaft für Neuropädiatrie und der Gesellschaft für Pädiatrische Onkologie und Hämatologie AWMF online, 2024 |
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| Ruutu T, de Wreede LC, van Biezen A, Brand R, Mohty M, Dreger P, Duarte R, Peters C, Garderet L, Schönland S, Gratwohl A, Niederwieser D, de Witte T, Kröger N |
Second allogeneic transplantation for relapse of malignant disease: retrospective analysis of outcome and predictive factors by the EBMT. |
Bone Marrow Transplant 2015, 50: 1542 |
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| In patients treated with allogeneic stem cell transplantation (SCT) for malignant disease who suffer from a relapse after the transplantation, the role of second allogeneic SCT is often uncertain. In a retrospective analysis, 2632 second allogeneic transplantations carried out for a relapse after the first transplantation were analyzed to define indications and identify predictive factors. Fifteen percent of the patients remained relapse-free until 5 years after the second SCT. Patients with CML had a better survival than patients with other diseases. In a multivariate analysis, factors associated with better survival were low disease burden, longer remission duration after the first transplantation, longer interval between the transplantations, younger age, absence of grade II-IV acute GvHD or chronic GvHD after the first transplantation, and later year of transplantation. The European Society for Blood and Marrow Transplantation risk score predicted the outcome. Using the same donor as in the first transplantation vs another donor had no predictive value for survival. Sibling donor was a favorable predictive factor. In conclusion, second allogeneic SCT offers a reasonable option especially for young patients with a long remission after the first transplantation and a low disease burden. The present findings do not support the usefulness of changing the donor for the second transplantation. |
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