Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2010-04, Vol.107 (16), p.7473-7478

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2010

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.