Clinical characteristics, treatment response and outcome were evaluated in children with Down's syndrome (DS) and acute lymphoblastic leukemia (ALL) as compared to other children with ALL (NDS). Sixty-one DS and 4049 NDS patients, receiving intensive antileukemic treatment during four consecutive trials (ALL-BFM 81, 83, 86 and 90) of the Berlin-Frankfurt-Mü nster Group (BFM), were retrospectively analyzed. DS and NDS children did not differ with respect to sex, leukocyte count, CNS leukemia and cytogenetic translocations. The DS cohort was slightly older (P = 0.04), presented predominantly with the common while lacking the T immunophenotype (P = 0.005), had a lower frequency of hyperdiploidy (P = 0.004) and tended to have a better initial steroid response (P = 0.057). Therapy-associated morbidity especially during high-dose methotrexate and a subsequent need for treatment modification occurred in 43% of all DS patients. Event-free survival (EFS) was slightly worse in children with DS (58 ± 8% vs 70 ± 1%, P = 0.14), mainly due to rather late bone marrow recurrences. However, EFS in DS patients was comparable to the NDS group once they either received treatment with no major modifications (65 ± 9% vs 70 ± 1%, P = 0.66) or were Ͻ6 years of age, irrespectively of therapy modifications (73 ± 9% vs 74 ± 1%, P = 0.7). Cox regression analysis revealed that DS was an adverse prognostic factor for patients having completed therapy (P = 0.0107), but was not prognostic at diagnosis (P = 0.103). Age у6 years, suboptimal treatment and infectious problems contributed to the slight inferior EFS in children with ALL and Down's syndrome. Therefore, most of these patients can be successfully treated if receiving intensive antileukemic treatment with no major modifications, but they require more sophisticated management of toxicity.
We report on the outcome of children with advanced primary myelodysplastic syndrome (MDS) transplanted from an HLAmatched sibling (MSD) or an unrelated donor (UD) following a preparative regimen with busulfan, cyclophosphamide and melphalan. Ninety-seven patients with refractory anemia with excess blasts (RAEB, n ¼ 53), RAEB in transformation (RAEB-T, n ¼ 29) and myelodysplasia-related acute myeloid leukemia (MDR-AML, n ¼ 15) enrolled in the European Working Group of MDS in Childhood (EWOG-MDS) 98 study and given hematopoietic stem cell transplantation (HSCT) were analyzed. Median age at HSCT was 11.1 years (range 1.4-19.0). Thirty-nine children were transplanted from an MSD, whereas 58 were given the allograft from a UD (n ¼ 57) or alternative family donor (n ¼ 1). Stem cell source was bone marrow (n ¼ 69) or peripheral blood (n ¼ 28). With a median follow-up of 3.9 years (range 0.1-10.9), the 5-year probability of overall survival is 63%, while the 5-year cumulative incidence of transplantation-related mortality (TRM) and relapse is 21% each. Age at HSCT greater than 12 years, interval between diagnosis and HSCT longer than 4 months, and occurrence of acute or extensive chronic graft-versus-host disease were associated with increased TRM. The risk of relapse increased with more advanced disease. This study indicates that HSCT following a myeloablative preparative regimen offers a high probability of survival for children with advanced MDS.
Summary:Children with Wilms tumor who have a particular risk of failure at relapse or at primary diagnosis were treated with high-dose chemotherapy (HDC) and autologous peripheral blood stem cell rescue in order to improve their probability of survival. Keywords: Wilms tumor; high-dose chemotherapy; autologous bone marrow transplantation A child with newly diagnosed Wilms tumor (WT) has a probability of about 85% of being cured with multimodal treatment nowadays. Current treatment strategies stratify intensity and scheduling of the different treatment modalities -surgery, radiation and chemotherapy -according to biologic and prognostic features of the initial disease, most importantly, stage and histology. Three large multiinstitutional study groups have contributed to this development: the National Wilms Tumor Study (NWTS), USA, 1-3 the United Kingdom Children's Cancer Study Group 4,5 and the International Society of Pediatric Oncology (SIOP). [6][7][8][9] For the 15% of patients with relapse or refractory disease, attempts have been made to use a similar risk-adapted strategy. These efforts were based upon the analysis of Grundy et al 10 demonstrating a 3-year survival of 30% in 367 patients who relapsed following treatment within studies NWTS-2 and -3. The authors identified prognostic factors with respect to time and site of relapse, histology and previous therapy, and used them to identify a good-risk group of relapsed patients who had a survival of >40% with conventional therapy. 10 For the complementary group of very high-risk patients, treatment alternatives were investigated. In phase II studies, single drugs or combinations gave the following results: single drug etoposide: 42% of response; 11 ifosfamide plus etoposide: overall response rate 39.5%; 12 etoposide and ifosfamide: 15% complete and 54% partial remission; 13 etoposide plus carboplatin: 70% response. 14 None of these approaches, however, could improve the long-term survival of these patients above 30%. 14 Consequently, dose-response strategies were investigated. Warkentin et al 15 who administered etoposide and thiotepa, reported eight out of 12 relapse-free survivors after 1 year. The Solid Tumor Registry of the EBMT reviewed 24
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