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The mutations of NPM1 and FLT3 -ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an NPM1 mutation reduces the negative prognostic impact of FLT3 -ITD in patients treated with conventional "3+7" induction. However, little information is available on their prognostic role with intensified regimens. Here, we investigated the efficacy of a fludarabine, high-dose cytarabine and idarubicin induction (FLAI) in 149 consecutive fit AML patients (median age 52) carrying the NPM1 and/or FLT3 -ITD mutation, treated from 2008 to 2018. One-hundred-and-twenty-nine patients achieved CR (86.6%). After a median follow up of 68 months, 3-year overall survival was 58.6%. Multivariate analysis disclosed that both NPM1 mut ( p &lt; 0.05) and ELN 2017 risk score ( p &lt; 0.05) were significant predictors of survival. NPM1 -mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant FLT3 -ITD ( p = 0.372), irrespective of FLT3 -ITD allelic burden. Moreover, in landmark analysis, performing allogeneic transplantation (HSCT) in first CR proved to be beneficial only in ELN 2017 high-risk patients. Our data indicate that FLAI exerts a strong anti-leukemic effect in younger AML patients with NPM1 mut and question the role of HSCT in 1st CR in NPM1 mut patients with concomitant FLT3 -ITD.

cancers

Fludarabine, High-Dose Cytarabine and Idarubicin-Based Induction May Overcome the Negative Prognostic Impact of FLT3-ITD in NPM1 Mutated AML, Irrespectively of FLT3-ITD Allelic Burden