Risk-stratified therapy for children with FLT3-ITD-positive acute myeloid leukemia: results from the JPLSG AML-05 study.

Acute myeloid leukemia harboring internal tandem duplication of FMS-like tyrosine kinase 3 (AML) is associated with poor prognosis. We evaluated the results of the AML-05 study, in which all AML patients were assigned to receive hematopoietic stem cell transplantation (HSCT) in the first remission (1CR). We also investigated the effects of additional genetic alterations on FLT3-ITD. The 5-year overall survival (OS) and event-free survival (EFS) rates among the 47 AML patients were 42.2 and 36.8%, respectively. The 5-year disease-free survival rate among 29 patients without induction failure was 58.4%. We defined the allelic ratio (AR) of FLT3-ITD to WT > 0.7 as high. Significant differences were found in OS (AR-high, 20% vs. AR-low, 66%, p < 0.001) and EFS (13 vs. 50%, p = 0.004). All five patients with concurrent NPM1 mutations survived, while seven of eight patients who expressed the NUP98-NSD1 chimera failed to achieve 1CR and died. Multivariate analysis revealed that AR > 0.7 and expression of the NUP98-NSD1 chimera strongly impacted OS and EFS. Although all the AML patients received HSCT at 1CR, the treatment outcome of AML patients did not improve compared with those in a previous study. Heterogeneity was observed among AML patients.