Prognostic impact of low allelic ratio FLT3-ITD and NPM1 mutation in acute myeloid leukemia

Abstract

In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation (<i>NPM1</i> mut)-positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication (<i>FLT3</i>-ITD) allele ratio (AR) <0.5 (low AR) has a favorable prognosis, and allogeneic hematopoietic stem cell transplant (allo-HSCT) in the first complete remission (CR1) period is not actively recommended. We studied 147 patients with <i>FLT3</i>-ITD gene mutation-positive AML, dividing them into those with low AR and those with AR of ≥0.5 (high AR), and examined the prognostic impact according to allo-HSCT in CR1. Although <i>FLT3</i>-ITD AR and <i>NPM1</i> mut are used in the prognostic stratification, we found that <i>NPM1</i> mut-positive AML with <i>FLT3</i>-ITD low AR was not associated with favorable outcome (overall survival [OS], 41.3%). Moreover, patients in this group who underwent allo-HSCT in CR1 had a significantly more favorable outcome than those who did not (relapse-free survival [RFS] <i>P</i> = .013; OS <i>P</i> = .003). Multivariate analysis identified allo-HSCT in CR1 as the sole favorable prognostic factor (RFS <i>P</i> < .001; OS <i>P</i> < .001). The present study found that prognosis was unfavorable in <i>NPM1</i> mut-positive AML with <i>FLT3</i>-ITD low AR when allo-HSCT was not carried out in CR1.