title: Effect of NPM1 and FLT3 mutations on the outcomes of elderly patients with acute myeloid leukemia receiving standard chemotherapy.
abstract: BACKGROUND
  The effect of prognostically important gene mutations (MUTs), nucleophosmin (nucleolar phosphoprotein B23, numatrin) (NPM1) and fms-related tyrosine kinase 3 (FLT3), in elderly patients with acute myeloid leukemia (AML) is not well defined.
  
  
  METHODS
  We analyzed 557 patients, 65 years of age or older with newly diagnosed AML, treated at our institution between 2000 and 2010 with cytotoxic chemotherapy. NPM1 and FLT3 analysis were available in 146 patients (26%) and 388 patients (70%), respectively.
  
  
  RESULTS
  NPM1 and FLT3 MUTs occurred in 16% and 12% of patients, respectively. No difference in median overall survival was observed between FLT3-MUT and NPM1-MUT patients who received cytotoxic chemotherapy. Outcome was significantly better among patients with NPM1-MUT/FLT3-wild type (WT) genotype (n = 14) compared with patients carrying FLT3/NPM1 genotypes other than NPM1-MUT/FLT3-WT (n = 125). The complete remission rates were 71% and 49%, respectively (P = .11). The median survival was 21.5 months vs. 9.0 months and estimated 2-year survival rates were 51% vs. 38%, respectively (P = .003). NPM1 and FLT3 MUTs appear to occur less frequently in elderly AML patients. The prognostic effect of isolated NPM1- or isolated FLT3-MUT is minimal.
  
  
  CONCLUSIONS
  Elderly AML patients with NPM1-MUT/FLT3-WT genotype have significantly improved outcomes compared with patients with other NPM1/FLT3 genotypes when treated with cytotoxic chemotherapy.
authors.affiliation: Department of Leukemia, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Naval
authors.initials: N
authors.lastname: Daver
authors.forename: Theresa
authors.initials: T
authors.lastname: Liu Dumlao
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Naveen
authors.initials: N
authors.lastname: Pemmaraju
authors.forename: Aziz
authors.initials: A
authors.lastname: Nazha
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Jorges
authors.initials: J
authors.lastname: Cortes
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics* / Q000378:metabolism
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: Acute myeloid leukemia; Cytotoxic chemotherapy; Elderly; FLT3; NPM1