title: Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine.
abstract: A phase II clinical trial with single-agent decitabine was conducted in older patients (>or=60 years) with previously untreated acute myeloid leukemia (AML) who were not candidates for or who refused intensive chemotherapy. Subjects received low-dose decitabine at 20 mg/m(2) i.v. over 1 h on days 1 to 10. Fifty-three subjects enrolled with a median age of 74 years (range, 60-85). Nineteen (36%) had antecedent hematologic disorder or therapy-related AML; 16 had complex karyotypes (>or=3 abnormalities). The complete remission rate was 47% (n = 25), achieved after a median of three cycles of therapy. Nine additional subjects had no morphologic evidence of disease with incomplete count recovery, for an overall response rate of 64% (n = 34). Complete remission was achieved in 52% of subjects presenting with normal karyotype and in 50% of those with complex karyotypes. Median overall and disease-free survival durations were 55 and 46 weeks, respectively. Death within 30 days of initiation of treatment occurred in one subject (2%), death within 8 weeks in 15% of subjects. Given the DNA hypomethylating effect of decitabine, we examined the relationship of clinical response and pretreatment level of miR-29b, previously shown to target DNA methyltransferases. Higher levels of miR-29b were associated with clinical response (P = 0.02). In conclusion, this schedule of decitabine was highly active and well tolerated in this poor-risk cohort of older AML patients. Levels of miR-29b should be validated as a predictive factor for stratification of older AML patients to decitabine treatment.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, and Center for Biostatistics, Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA. william.blum@osumc.edu
authors.forename: William
authors.initials: W
authors.lastname: Blum
authors.forename: Ramiro
authors.initials: R
authors.lastname: Garzon
authors.forename: Rebecca B
authors.initials: RB
authors.lastname: Klisovic
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schwind
authors.forename: Alison
authors.initials: A
authors.lastname: Walker
authors.forename: Susan
authors.initials: S
authors.lastname: Geyer
authors.forename: Shujun
authors.initials: S
authors.lastname: Liu
authors.forename: Violaine
authors.initials: V
authors.lastname: Havelange
authors.forename: Heiko
authors.initials: H
authors.lastname: Becker
authors.forename: Larry
authors.initials: L
authors.lastname: Schaaf
authors.forename: Jon
authors.initials: J
authors.lastname: Mickle
authors.forename: Hollie
authors.initials: H
authors.lastname: Devine
authors.forename: Cheryl
authors.initials: C
authors.lastname: Kefauver
authors.forename: Steven M
authors.initials: SM
authors.lastname: Devine
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Chan
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: Michael R
authors.initials: MR
authors.lastname: Grever
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Miguel
authors.initials: M
authors.lastname: Villalona-Calero
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015331:Cohort Studies; D019175:DNA Methylation; D000077209:Decitabine; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D000077209:Decitabine; D001374:Azacitidine