Phase II Study of Low-Dose Decitabine in Patients With Chronic Myelogenous Leukemia Resistant to Imatinib Mesylate
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- Jean-Pierre J. Issa
- From the Department of Leukemia and Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
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- Vazganush Gharibyan
- From the Department of Leukemia and Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
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- Jorge Cortes
- From the Department of Leukemia and Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
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- Jaroslav Jelinek
- From the Department of Leukemia and Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
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- Gail Morris
- From the Department of Leukemia and Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
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- Srdan Verstovsek
- From the Department of Leukemia and Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
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- Moshe Talpaz
- From the Department of Leukemia and Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
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- Guillermo Garcia-Manero
- From the Department of Leukemia and Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
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- Hagop M. Kantarjian
- From the Department of Leukemia and Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
抄録
<jats:sec><jats:title>Purpose</jats:title><jats:p> To determine the activity of decitabine, a DNA methylation inhibitor, in imatinib-refractory or intolerant chronic myelogenous leukemia. </jats:p></jats:sec><jats:sec><jats:title>Materials and Methods</jats:title><jats:p> Thirty-five patients were enrolled in this phase II study (12 in chronic phase, 17 in accelerated phase, and six in blastic phase). Decitabine was administered at 15 mg/m<jats:sup>2</jats:sup> intravenously over 1 hour daily, 5 days a week for 2 weeks. DNA methylation was measured using a LINE1 bisulfite/pyrosequencing assay. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Complete hematologic responses were seen in 12 patients (34%) and partial hematologic responses in seven patients (20%), for an overall hematologic response rate of 54% (83% in chronic phase, 41% in accelerated phase, and 34% in blastic phase). Major cytogenetic responses were observed in six patients (17%), and minor cytogenetic responses were seen in 10 patients (29%) for an overall cytogenetic response rate of 46%. Median response duration was 3.5 months (range, 2 to 13+ months). Myelosuppression was the major adverse effect, with neutropenic fever in 28 (23%) of 124 courses of therapy. LINE1 methylation decreased from 71.3% ± 1.4% (mean ± standard error of the mean) to 60.7% ± 1.4% after 1 week, 50.9% ± 2.4% after 2 weeks, and returned to 66.5% ± 2.7% at recovery of counts (median, 46 days). LINE1 methylation at the end of week 1 did not correlate with subsequent responses. However, at day 12, the absolute decrease in methylation was 14.5% ± 3.0% versus 26.8% ± 2.7% in responders versus nonresponders (P = .007). </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Decitabine induces hypomethylation and has clinical activity in imatinib refractory chronic myelogenous leukemia. We hypothesize that the inverse correlation between hypomethylation 2 weeks after therapy and response is due to a cell death mechanism of response, whereby resistant cells can withstand more hypomethylation. </jats:p></jats:sec>
収録刊行物
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- Journal of Clinical Oncology
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Journal of Clinical Oncology 23 (17), 3948-3956, 2005-06-10
American Society of Clinical Oncology (ASCO)
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詳細情報 詳細情報について
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- CRID
- 1360292620527442304
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- NII論文ID
- 30022792117
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- ISSN
- 15277755
- 0732183X
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