Prognostic Significance of FLT3 Mutations in Paired Initial and Relapse Marrow Samples of Acute Myeloid Leukemia Excluding Acute Promyelocytic Leukemia.

Fms-Like tyrosine kinase 3 (FLT3) mutations are related to poor prognosis in acute myeloid leukemia (AML), with the exception of acute promyelocytic leukemia (APL), in which the prognostic significance of this mutation is not firmly established even though it is more frequent than other FAB subtypes. We investigated FLT3 internal tandem duplications (FLT3/ITD) and/or D835 point mutations in both initial and relapse marrow samples from 120 AML patients, excluding APL. FLT3/ITDs were found in 18 initial and 16 relapse samples (15.0 and 13.3%, respectively). D835 mutations were found in one initial sample and 4 relapse samples. Two cases acquired FLT3/ITD at relapse, 4 cases lost mutations at relapse, and one had a different allele of FLT3/ITD at relapse. Patients who had FLT3/ITDs at initial diagnosis showed shorter median duration from diagnosis to relapse and shorter overall survival compared with those without mutations (median duration to relapse: 8.3 and 11.0 months, respectively, P = 0.074; overall survival: 12.2 and 20.8 months, respectively, P = 0.058). These findings were more pronounced when the FLT3/ITDs were acquired at relapse or discrepant patterns were noted between diagnosis and relapse (median duration to relapse: P = 0.047 and 0.044, respectively; overall survival: P = 0.002 and 0.038, respectively). In conclusion, the present study showed that patients with AML had heterogeneous patterns of FLT3/ITD or D835 mutations, either acquisition or loss of the mutations at relapse. The overall survival and relapse-free survival times were significantly shorter in the mutation acquisition group than in those with mutation loss at relapse.