ORIGINAL ARTICLE Improved outcome of pediatric patients with acute

Abstract Despite recent advances in the treatment of children with acute megakaryoblastic leukemia (AMKL) using inten-sified treatment protocols, clear prognostic indicators, and treatment recommendations for this acute myeloid leukemia (AML) subgroup are yet to be defined. Here, we report the outcome of 97 pediatric patients with de novo AMKL (ex-cluding Down syndrome [DS]) enrolled in the prospective multicenter studies AML-BFM 98 and AML-BFM 04 (1998-2014). AMKL occurred in 7.4 % of pediatric AML cases, at younger age (median 1.44 years) and with lower white blood cell count (mean 16.5×109/L) as compared to other AML subgroups. With 60±5 %, children with AMKL had a lower 5-year overall survival (5-year OS; vs. 68±1 %, Plog rank=0.038). Yet, we achieved an improved 5-year OS in AML-BFM 04 compared to AML-BFM 98 (70±6 % vs. 45± 8 %, Plog rank=0.041). Allogeneic hematopoietic stem cell transplantation in first remission did not provide a significant survival benefit (5-year OS 70±11 % vs. 63±6 %; PMantel-Byar=0.85). Cytogenetic data were available for n=78 pa-tients. AMKL patients with gain of chromosome 21 had a superior 5-year OS (80±9 %, Plog rank=0.034), whereas trans-location t(1;22)(p13;q13) was associated with an inferior 5-year event-free survival (38±17 %, Plog rank=0.04). However, multivariate analysis showed that treatment response (bone marrow morphology on day 15 and 28) was the only indepen-dent prognostic marker (RR=4.39; 95 % CI, 1.97–9.78). In-terestingly, GATA1-mutations were detected in six patients (11 %) without previously known trisomy 21. Thus, AMKL (excluding DS) remains an AML subgroup with inferior out-come. Nevertheless, with intensive therapy regimens, a steep increase in the survival rates was achieved