Distinct clinico-biological features in AML patients with low allelic ratio FLT3 -ITD: role of allogeneic stem cell transplantation in first remission

The mutant burden of FLT3 -ITD modulates its prognostic impact on patients with acute myeloid leukemia (AML). However, for patients with low allelic ratio (AR) FLT3 -ITD ( FLT3 -ITD low , AR < 0.5), clinical features, as well as genomic and transcriptomic profiles remain unclear, and evidence supporting allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) remains controversial. This study aimed to elucidate the genomic features, prognosis, and transplantation outcome of FLT3 -ITD Iow in AML patients with intermediate-risk cytogenetics. FLT3 -ITD low was associated with a negative enrichment of the leukemic stem cell signature, a marked enrichment of the RAS pathway, and with higher frequencies of RAS pathway mutations, different from those with FLT3 -ITD high . Concurrent CEBPA double mutations were favorable prognostic factors, whereas MLL- PTD, and mutations in splicing factors were unfavorable prognostic factors in FLT3 -ITD low patients. Patients with FLT3 -ITD low had a shorter overall survival (OS) and event-free survival (EFS) than those with FLT3 wt . Allo-HSCT in CR1 was associated with a significantly longer OS and EFS compared with postremission chemotherapy in patients with FLT3 -ITD low . In conclusion, FLT3 -ITD low is associated with different mutational and transcriptomic profiles compared with FLT3 -ITD high . The presence of concomitant poor-risk mutations exert negative prognostic impacts in patients with FLT3 -ITD low , who markedly benefit from allo-HSCT in CR1.