Combination of FLT3-ITD Allelic Ratio, NPM1 Mutation, and Immunophenotypic Markers to Modulate Outcome Prediction in Patients with Normal Karyotype Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation

Abstract

NPM1 mutation status and the allelic ratio (AR) of FLT3-internal tandem duplication (FLT3-ITD) are routinely tested for disease risk stratification in patients with normal karyotype (NK) acute myelogenous leukemia (AML); however, the predictive impact of immunophenotypic markers on different NPM1/FLT3 genotypes remains unclear. We performed a retrospective analysis of 423 patients with NK-AML subclassified into groups based on NPM1/FLT3 genotype. Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 124 of 423 patients (29%) and was significantly associated with longer event-free survival (EFS) and overall survival (OS), except for patients with the favorable genotype, defined as mutated NPM1 (NPM1^mut) combined with normal FLT3 status (FLT3-ITD^neg) or FLT3-ITD AR <.5 (FLT3-ITD^low). A subset of AML patients bearing the favorable NPM1^mut/FLT3-ITD^neg/low genotype share similar outcomes with AML patients who have the intermediate FLT3/NPM1 genotype defined by normal NPM1 (NPM1^wt) and FLT3-ITD^neg/low. In these individuals, the lack of CD13 expression (CD13^neg) was associated with shorter EFS (P = .041) and OS (P = .017). CD13^neg was an independent predictor for shorter OS (hazard ratio, 1.985; P = .028).