title: The value of molecular stratification for CEBPA(DM) and NPM1(MUT) FLT3(WT) genotypes in older patients with acute myeloid leukaemia.
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.
authors: Department of Haematology, University College London Cancer Institute, London, UK.
authors: Glenda J
authors: GJ
authors: Dickson
authors: Department of Haematology, University College London Cancer Institute, London, UK.
authors: Sophia
authors: S
authors: Bustraan
authors: Department of Haematology, Cardiff University School of Medicine, Cardiff, UK.
authors: Robert K
authors: RK
authors: Hills
authors: Department of Haematology, University College London Cancer Institute, London, UK.
authors: Akbar
authors: A
authors: Ali
authors: Department of Haematology, University College London Hospital, London, UK.
authors: Anthony H
authors: AH
authors: Goldstone
authors: Department of Haematology, Cardiff University School of Medicine, Cardiff, UK.
authors: Alan K
authors: AK
authors: Burnett
authors: Department of Haematology, University College London Cancer Institute, London, UK.
authors: David C
authors: DC
authors: Linch
authors: Department of Haematology, University College London Cancer Institute, London, UK.
authors: Rosemary E
authors: RE
authors: Gale
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: CEBPA genotype; NPM1 and FLT3 genotype; acute myeloid leukaemia; molecular prognostication