Improved outcome of pediatric patients with acute megakaryoblastic leukemia in the AML-BFM 04 trial
Jana Schweitzer1, Martin Zimmermann, Mareike Rasche
1Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Insights
Pediatric acute megakaryoblastic leukemia (AMKL) has a poorer prognosis than other acute myeloid leukemia (AML) subtypes. Intensified treatment protocols significantly improved survival rates in AMKL patients, highlighting treatment response as a key prognostic factor.
Area of Science:
- Pediatric Hematology Oncology
- Leukemia Research
- Clinical Trial Analysis
Background:
- Acute megakaryoblastic leukemia (AMKL) is a distinct subgroup of acute myeloid leukemia (AML) in children.
- Despite treatment advances, prognostic indicators and optimal treatment strategies for pediatric AMKL remain unclear.
- This study analyzes outcomes for non-Down syndrome pediatric AMKL patients.
Purpose of the Study:
- To evaluate the outcomes of pediatric de novo AMKL patients treated within prospective multicenter studies.
- To identify prognostic factors influencing survival in this AML subgroup.
- To assess the impact of intensified treatment protocols on AMKL patient survival.
Main Methods:
- Analysis of 97 pediatric patients with de novo AMKL (excluding Down syndrome) from AML-BFM 98 and AML-BFM 04 studies (1998-2014).
- Comparison of clinical characteristics and survival rates with other AML subgroups.
- Evaluation of cytogenetic data, including gain of chromosome 21 and t(1;22) translocation.
- Assessment of treatment response and the role of allogeneic hematopoietic stem cell transplantation.
Main Results:
- Pediatric AMKL patients were younger with lower white blood cell counts compared to other AML subtypes.
- The 5-year overall survival (OS) for AMKL was 60%, lower than other AML groups (P=0.038).
- Survival significantly improved in the AML-BFM 04 study (70%) compared to AML-BFM 98 (45%) (P=0.041).
- Gain of chromosome 21 was associated with superior OS (80%), while t(1;22) translocation correlated with inferior event-free survival (38%).
- Treatment response (day 15 and 28 bone marrow morphology) was the sole independent prognostic marker (RR=4.39).
- Allogeneic stem cell transplantation in first remission did not show a significant survival benefit.
Conclusions:
- Pediatric AMKL (excluding Down syndrome) remains an AML subgroup with inferior outcomes.
- Intensified therapy regimens have led to a substantial increase in survival rates.
- Treatment response is the most critical independent prognostic factor for pediatric AMKL.
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 × 10(9)/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 %, P log 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 %, P log 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 %; P Mantel-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 %, P log rank = 0.034), whereas translocation t(1;22)(p13;q13) was associated with an inferior 5-year event-free survival (38 ± 17 %, P log 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.
