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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
Author(s) -
Dickson Glenda J.,
Bustraan Sophia,
Hills Robert K.,
Ali Akbar,
Goldstone Anthony H.,
Burnett Alan K.,
Linch David C.,
Gale Rosemary E.
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13873
Subject(s) - cebpa , npm1 , genotype , medicine , cohort , gastroenterology , oncology , biology , genetics , mutation , karyotype , gene , chromosome
Summary 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.