Adverse impact of a high allelic burden FLT3-ITD mutation on allogeneic hematopoietic stem cell transplantation in patients with cytogenetically normal AML.

Risks associated with the FLT3-ITD mutation in patients receiving chemotherapy alone for cytogenetic normal acute myeloid leukemia (CN-AML) depend on the allelic ratio (AR) and concomitant NPM1 mutation. Nevertheless, their prognostic ability after allogeneic hematopoietic cell transplantation (allo-HCT) remains undetermined. Moreover, previous studies have revealed that haploidentical transplantation improves outcomes of FLT3-ITD patients. To elucidate whether this alteration also impacts prognosis of myeloablative allo-HCT upon first remission, we retrospectively reviewed the prognostic ability of FLT3-ITD mutations in 205 CN-AML patients. Our analysis demonstrated that FLT3-ITD AR was closely related to pretransplant MRD and induction response. Multivariate analysis showed that high-AR FLT3-ITD, pretransplant MRD and induction response were independent risk factors for CN-AML. In addition, we presented evidence that the high-AR FLT3-ITD patient prognosis was not overcome by haploidentical transplantation, but was markedly improved by cGVHD. More importantly, among patients with negative pretransplant MRD, high-AR FLT3-ITD patients did not have increased relapse risk, compared to low-AR FLT3-ITD and wild-type FLT3 patients. Our findings will aid in accurate prognostic stratification of FLT3-ITD patients. We also recommend further targeted and coordinated approaches to sustain durable remission following induction chemotherapy and allo-HCT in this high-risk patient population.