Prognostic value of the mutation types and dynamics of FLT3‐ITD in acute myeloid leukemia

Abstract Objective The prognostic value of the mutation types and dynamics of FLT3 ‐ITD in acute myeloid leukemia (AML) and other known factors were studied. Methods Initial and follow‐up samples from 45 AML patients with FLT3 ‐ITD mutations were analyzed by fragment length analysis, Sanger sequencing, and next‐generation sequencing. Results Some patients (13%) had multiple FLT3 ‐ITD mutations, and many of them had acute promyelocytic leukemia (APL). FLT3 ‐ITD mutations were classified according to mutation types, including duplication‐only FLT3 ‐ITD (52%) and FLT3 ‐ITD with duplications and insertions (dup + ins) (48%). The dup + ins FLT3 ‐ITD variant was independently associated with poor prognosis among non‐APL patients (odds ratio, 2.92) in addition to FLT3 ‐ITD with ≥50% variant allele frequency (VAF). The VAFs of FLT3 ‐ITD were low (median 2.2%) when detected during morphologic complete remission (CR) after conventional chemotherapy; however, in two patients treated with gilteritinib after relapse, the VAFs of FLT3 ‐ITD were much higher (>95% and 8.1%) in the morphologic CR state. Conclusions The type of FLT3 ‐ITD mutation is important in prognosis, and the dup + ins type of FLT3 ‐ITD can be an indicator of poor prognosis. In addition, the FLT3 ‐ITD mutation status may unexpectedly not match the morphologic examination results after gilteritinib treatment.