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.

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 (NPM1mut) combined with normal FLT3 status (FLT3-ITDneg) or FLT3-ITD AR <.5 (FLT3-ITDlow). A subset of AML patients bearing the favorable NPM1mut/FLT3-ITDneg/low genotype share similar outcomes with AML patients who have the intermediate FLT3/NPM1 genotype defined by normal NPM1 (NPM1wt) and FLT3-ITDneg/low. In these individuals, the lack of CD13 expression (CD13neg) was associated with shorter EFS (P = .041) and OS (P = .017). CD13neg was an independent predictor for shorter OS (hazard ratio, 1.985; P = .028).

Acute myeloid leukemia with myelodysplasia-related changes diagnosed with multilineage dysplasia alone demonstrates a superior clinical outcome.

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) generally confers poor prognosis; however, the clinical outcome remains heterogeneous. We sought to further stratify this subentity of AML by performing a retrospective analysis of 179 adult patients with AML-MRC diagnosed at our institution. Based on 2016 World Health Organization diagnostic criteria, 44 (25%) patients had multilineage dysplasia alone (AML-MRC-M), 74 (41%) had history of myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative disease (AML-MRC-H), and 61 (34%) had MDS-related cytogenetics (AML-MRC-C). AML-MRC-M and hematopoietic stem cell transplantation (HSCT) were associated with prolonged event-free survival (EFS) (P = 0.0051 and P < 0.0001, respectively) and overall survival (OS) (P = 0.0015 and P < 0.0001, respectively), whereas AML-MRC-C and age ≥60 years were associated with shorter EFS (P = 0.028 and P = 0.015, respectively) and OS (P = 0.021 and P = 0.013, respectively). Of note, NPM1mut did not affect the patient's outcome. Multivariable analysis confirmed HSCT and AML-MRC-C as independent predictors for EFS (P < 0.0001 and P = 0.0342, respectively) and OS (P < 0.0001 and P = 0.0295, respectively). AML-MRC-M was an independent predictor for OS (P = 0.0449). When compared with a control group of 105 patients with normal karyotype AML not otherwise specified (NK-AML-NOS), patients with AML-MRC-M had similar EFS and OS (P = 0.99 and P = 0.91, respectively). However, AML-MRC-H and AML-MRC-C were associated with shorter EFS and OS (P = 0.0002 and P < 0.0001, respectively) than the same control group. In a subset of patients, next-generation sequencing analysis showed AML-MRC-M was associated with ASXL1 mutation compared with NK-AML (56% vs 6%). In conclusion, AML-MRC-M demonstrates a superior clinical outcome compared with the rest of the AML-MRC group. They have comparable outcomes to NK-AML-NOS, and these data suggest AML-MRC-M may be considered not to be classified in the same group as patients with other AML-MRC.