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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

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

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  • Medientyp: E-Artikel
  • Titel: Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine
  • 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
  • Erschienen: Proceedings of the National Academy of Sciences, 2010
  • Erschienen in: Proceedings of the National Academy of Sciences
  • Sprache: Englisch
  • DOI: 10.1073/pnas.1002650107
  • ISSN: 0027-8424; 1091-6490
  • Schlagwörter: Multidisciplinary
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p> 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/m <jats:sup>2</jats:sup> 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% ( <jats:italic>n</jats:italic> = 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% ( <jats:italic>n</jats:italic> = 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 <jats:italic>miR-29b</jats:italic> , previously shown to target DNA methyltransferases. Higher levels of <jats:italic>miR-29b</jats:italic> were associated with clinical response ( <jats:italic>P</jats:italic> = 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 <jats:italic>miR-29b</jats:italic> should be validated as a predictive factor for stratification of older AML patients to decitabine treatment. </jats:p>
  • Zugangsstatus: Freier Zugang