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The value of molecular stratification for CEBPA DM and NPM1 MUT FLT3 WT genotypes in older patients with acute myeloid leukaemia

Dickson, Glenda J., Bustraan, Sophia, Hills, Robert Kerrin, Ali, Akbar, Goldstone, Anthony H., Burnett, Alan, Linch, David C. and Gale, Rosemary E. 2016. 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 172 (4) , pp. 573-580. 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 (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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Uncontrolled Keywords: acute myeloid leukaemia; molecular prognostication; CEBPA genotype; NPM1 and FLT3 genotype.
Publisher: Wiley-Blackwell
ISSN: 0007-1048
Date of Acceptance: 30 October 2015
Last Modified: 19 Oct 2019 02:47
URI: http://orca-mwe.cf.ac.uk/id/eprint/103788

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