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Older adult patients (≥60 years) with acute myeloid leukaemia (AML) are generally considered to be poor-risk and there is limited information available regarding risk stratification based on molecular characterization in this age group, particularly for the double-mutant CEBPA (CEBPA(DM) ) genotype. To investigate whether a molecular favourable-risk genotype can be identified, we investigated CEBPA, NPM1 and FLT3 status and prognostic impact in a cohort of 301 patients aged 60 years or more with intermediate-risk cytogenetics, all treated intensively. Overall survival (OS) at 1 year was highest in the 12 patients (4%) that were CEBPA(DM) compared to the 76 (28%) with a mutant NPM1 and wild-type FLT3 (NPM1(MUT) FLT3(WT) ) genotype or all other patients (75%, 54%, 33% respectively), with median survival 15·2, 13·6 and 6·6 months, although the benefit was short-term (OS at 3 years 17%, 29%, 12% respectively). Combination of the CEBPA(DM) and NPM1(MUT) FLT3(WT) genotype patients defined a molecular group with favourable prognosis (P < 0·0001 in multivariate analysis), with 57% of patients alive at 1 year compared to 33% for all other patients. Knowledge of genotype in older cytogenetically intermediate-risk patients might influence therapy decisions.

Original publication

DOI

10.1111/bjh.13873

Type

Journal article

Journal

Br J Haematol

Publication Date

02/2016

Volume

172

Pages

573 - 580

Keywords

CEBPA genotype, NPM1 and FLT3 genotype, acute myeloid leukaemia, molecular prognostication, Aged, Aged, 80 and over, CCAAT-Enhancer-Binding Proteins, Female, Genotype, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute, Male, Middle Aged, Mutation, Nuclear Proteins, Prognosis, Risk Assessment, Risk Factors, Treatment Outcome, fms-Like Tyrosine Kinase 3