title: Outcome of patients with FLT3-mutated acute myeloid leukemia in first relapse.
abstract: Mutations of Fms-like tyrosine kinase-3 (FLT3) have been described in about 30% of patients with acute myeloid leukemia (AML) and are associated with a shorter disease-free and overall survival after initial therapy. We sought to examine whether the presence of these mutations in relapsed disease was also associated with a poor response to salvage chemotherapy by comparing the outcome of 34 patients with diploid cytogenetics and mutated FLT3 (internal tandem duplication mutation, ITD) to 69 patients with normal karyotype and wild-type FLT3 (FLT3-WT) in first relapse. On univariate analysis, patients with mutated FLT3 were less likely to achieve a CR to first salvage compared to FLT3-WT patients (24% vs. 41%; P=0.09). Furthermore, survival was longer for the FLT3-WT patients achieving a second CR after salvage compared to FLT3-mutated patients (P=0.017). Overall, patients with mutated FLT3 had a shorter survival from the time of relapse compared to those with FLT3-WT (P<0.001). The adverse prognostic impact of FLT3 mutations appears to persist beyond the initial treatment.
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. fravandi@mdanderson.org
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Charles
authors.initials: C
authors.lastname: Koller
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Mark
authors.initials: M
authors.lastname: Brandt
authors.forename: Deborah
authors.initials: D
authors.lastname: Kennedy
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Miloslav
authors.initials: M
authors.lastname: Beran
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015331:Cohort Studies; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D011379:Prognosis; D012008:Recurrence; D016879:Salvage Therapy; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3