Dickson, GJ; Bustraan, S; Hills, RK; Ali, A; Goldstone, AH; Burnett, AK; Linch, DC; Dickson, GJ; Bustraan, S; Hills, RK; Ali, A; Goldstone, AH; Burnett, AK; Linch, DC; Gale, RE; - view fewer (2015) The value of molecular stratification for CEBPA_DM and NPM1_MUT_FLT3_WT genotypes in older patients with acute myeloid leukaemia. British Journal of Haematology 10.1111/bjh.13873.

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Abstract

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 (CEBPADM) 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 CEBPADM compared to the 76 (28%) with a mutant NPM1 and wild-type FLT3 (NPM1MUTFLT3WT) 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 CEBPADM and NPM1MUTFLT3WT 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.

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