title: Outcome of older adults with cytogenetically normal AML (CN-AML) and FLT3 mutations.
abstract: AML patients under the age of 60 whose blasts harbor a FLT3 internal tandem duplication (ITD) mutation have a higher relapse rate and inferior survival compared to those without this mutation. To determine if FLT3ITD also carries a negative prognostic impact in older adults receiving therapies commonly used in this age group, we retrospectively analyzed outcomes of patients ≥60 years with CN-AML according to FLT3 mutation status. We identified 91 newly diagnosed CN-AML patients, 55 with wild-type FLT3 and 36 with FLT3ITD. Of the 91 patients, 36 received supportive care and/or experimental therapies while the remaining 55 received induction chemotherapy, followed by allogeneic SCT in 17 of these patients. Based on univariate analysis, advanced age at diagnosis was significantly associated with shorter overall survival (OS) (p<.0001) while intensive therapies were associated with improved OS (p<.0001). In a multivariate analysis that accounted for type of treatment, patient age, gender, and WBC count, FLT3ITD was significantly associated with shorter OS compared to wtFLT3 [p=.001; hazard ratio (HR)=2.23; 95% CI: 1.35-3.70]. Our data support the negative prognostic impact of FLT3ITD in older adults with CN-AML.
authors.affiliation: Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Harshabad
authors.initials: H
authors.lastname: Singh
authors.forename: Salma
authors.initials: S
authors.lastname: Asali
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Werner
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DeAngelo
authors.forename: Karen K
authors.initials: KK
authors.lastname: Ballen
authors.forename: Philip C
authors.initials: PC
authors.lastname: Amrein
authors.forename: Martha
authors.initials: M
authors.lastname: Wadleigh
authors.forename: Ilene
authors.initials: I
authors.lastname: Galinsky
authors.forename: Donna S
authors.initials: DS
authors.lastname: Neuberg
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fox
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.forename: Eyal C
authors.initials: EC
authors.lastname: Attar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D020080:Tandem Repeat Sequences / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3