Outcome of patients with FLT3-mutated acute myeloid leukemia in first relapse

Abstract

Mutations of Fms-like tyrosine kinase-3 (FLT3) have been described in about 30% of patients with acute myeloid leukemia (AML) and are associated with a shorter disease-free and overall survival after initial therapy. We sought to examine whether the presence of these mutations in relapsed disease was also associated with a poor response to salvage chemotherapy by comparing the outcome of 34 patients with diploid cytogenetics and mutated FLT3 (internal tandem duplication mutation, ITD) to 69 patients with normal karyotype and wild-type FLT3 (FLT3-WT) in first relapse. On univariate analysis, patients with mutated FLT3 were less likely to achieve a CR to first salvage compared to FLT3-WT patients (24% vs. 41%; P=0.09). Furthermore, survival was longer for the FLT3-WT patients achieving a second CR after salvage compared to FLT3-mutated patients (P=0.017). Overall, patients with mutated FLT3 had a shorter survival from the time of relapse compared to those with FLT3-WT (P<0.001). The adverse prognostic impact of FLT3 mutations appears to persist beyond the initial treatment.