Abstract
Despite recent advances in the treatment of children with acute megakaryoblastic leukemia (AMKL) using intensified 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 (excluding 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 patients. AMKL patients with gain of chromosome 21 had a superior 5-year OS (80 ± 9 %, Plog rank = 0.034), whereas translocation 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 independent prognostic marker (RR = 4.39; 95 % CI, 1.97–9.78). Interestingly, GATA1-mutations were detected in six patients (11 %) without previously known trisomy 21. Thus, AMKL (excluding DS) remains an AML subgroup with inferior outcome. Nevertheless, with intensive therapy regimens, a steep increase in the survival rates was achieved.Electronic supplementary materialThe online version of this article (doi:10.1007/s00277-015-2383-2) contains supplementary material, which is available to authorized users.
Highlights
Acute megakaryoblastic leukemia (AMKL), M7 according to the French-American-British (FAB) classification [1], is a specific subtype of acute myeloid leukemia (AML) that can be clearly distinguished from other subtypes because of its biological and clinical characteristics
Of 1316 pediatric patients with AML enrolled in the population-based studies AML-BFM 98 and AML-BFM 04, 97 (7.4 %) presented with de novo non-Down syndrome (DS)-AMKL
The overall outcome of AMKL was extremely poor in the early AML-BFM 87 trial (EFS 11±7 %, 5-year OS 21±9 %), which could be significantly improved in the following trials AML-BFM 93 and 98 (5-year Event-free survival (EFS) 41±6 %, 5year OS 49±6 %) [2] by introducing idarubicin as well as high-dose cytarabine plus mitoxantrone to the protocol
Summary
Acute megakaryoblastic leukemia (AMKL), M7 according to the French-American-British (FAB) classification [1], is a specific subtype of acute myeloid leukemia (AML) that can be clearly distinguished from other subtypes because of its biological and clinical characteristics. In contrast to DS-AMKL (∼80 % survival), non-DS-AMKL is an AML subgroup associated with poor prognosis. Within the AML-BFM studies, the poor outcome of nonDS-AMKL in the AML-BFM 87 trial (5-year event-free survival [5-year EFS] 11±7 %, 5-year overall survival [5-year OS] 21±9 %) could be improved by intensifying the therapy in the AML-BFM 93 and 98 trials (5-year EFS 41±6 %, 5year OS 49±6 %) [2]. Whereas some study groups treat nonDS-AMKL as very high risk, recommending allogeneic hematopoietic stem cell transplantation (HSCT) during first complete remission (CR1) [5], other study groups obtained superior survival rates with intensive chemotherapy alone, which were not further increased by allogeneic HSCT [8]
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