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Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine.

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Blum, William Garzon, Ramiro Klisovic, Rebecca B Schwind, Sebastian Walker, Alison Havelange, Violaine [UCL] Marcucci, Guido

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2010
Language Anglais
Journal information "Proceedings of the National academy of sciences of the United States of America" - Vol. 107, no.16, p. 7473-8 (2010)
Peer reviewed yes
Publisher National academy of sciences ((United States) [S.l.])
issn 0027-8424
e-issn 1091-6490
Publication status Publié
MESH Subject Aged ; Karyotyping ; Leukemia, Myeloid, Acute ; Male ; MicroRNAs ; Middle Aged ; Remission Induction ; Treatment Outcome ; Aged, 80 and over ; Antimetabolites, Antineoplastic ; Azacitidine ; Cohort Studies ; DNA Methylation ; Disease-Free Survival ; Female ; Humans
Links
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Bibliographic reference Blum, William ; Garzon, Ramiro ; Klisovic, Rebecca B ; Schwind, Sebastian ; Walker, Alison ; et. al. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine.. In: Proceedings of the National academy of sciences of the United States of America, Vol. 107, no.16, p. 7473-8 (2010)
Permanent URL http://hdl.handle.net/2078/122148