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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 <italic>miR-29b</italic> 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 <italic>miR-29b</italic> 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: National Academy of Sciences, 2010
  • Erschienen in: Proceedings of the National Academy of Sciences of the United States of America
  • Sprache: Englisch
  • ISSN: 0027-8424
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <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/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.</p>
  • Zugangsstatus: Freier Zugang