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

William Blum, Ramiro Garzon, Rebecca B. Klisovic, Sebastian Schwind, Alison Walker, Susan Geyer, Shujun Liu, Violaine Havelange, Heiko Becker, Larry Schaaf, Jon Mickle, Hollie Devine, Cheryl Kefauver, Steven M. Devine, Kenneth K. Chan, Nyla A. Heerema, Clara D. Bloomfield, Michael R. Grever, John C. Byrd, Miguel Villalona-CaleroCarlo M. Croce, Guido Marcucci

Research output: Contribution to journalArticlepeer-review

383 Scopus citations

Abstract

A phase II clinical trial with single-agent decitabine was conducted in older patients (≥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/m2 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 (≥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.

Original languageEnglish (US)
Pages (from-to)7473-7478
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number16
DOIs
StatePublished - Apr 20 2010

Keywords

  • Azanucleoside
  • Methylation
  • microRNA

ASJC Scopus subject areas

  • General

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