期刊
LEUKEMIA RESEARCH
卷 66, 期 -, 页码 1-7出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2017.12.009
关键词
AML; DCAG; Decitabine; Vitamin C; Elderly; TET2
资金
- National Natural Science Foundation of the People's Republic of China [81070437, 81270614, 81300379, 81570134, 81570141, 81522001, 81200362]
- National Public Health Grand Research Foundation [201202017]
- Priority Academic Program Development of Jiangsu Higher Education Institute [JX10231801]
- Key Project of Jiangsu province Health Agency [K201107]
Background: Decitabine is widely used in the treatment of acute myeloid leukemia (AML) in elderly patients. Low-dose Vitamin C has also been indicated to induce DNA demethylation M the cellular level. However, little is known whether low-dose Vitamin C has a synergistic effect with decitabine in clinic. Methods: The effect of combined low-dose Vitamin C and decitabine on cell proliferation, the cell cycle, apoptosis and the expression level and activity of TET2 was investigated in HL60 and NB4 human leukemic cells. Additionally, we analyzed the clinical outcomes of 73 elderly AML patients who received A-DCAG (intravenous Vitamin C [IVC] plus DCAG [n = 39]) or DCAG (n = 34) treatment. Results: We found that low-dose Vitamin C and decitabine has a synergistic efficacy on proliferation, apoptosis, TET2 expression and activity, compared to drug-alone treatment in HL60 and NB4 cell lines in vitro. In clinic, feasibility and safety evaluations revealed that patients who received A-DCAG regimen have a higher complete remission (CR) rate than those who received the DCAG regimen (79.92% vs. 44.11%; P = 0.004) after one cycle of chemotherapy. The median overall survival (OS) was better in the A-DCAG group compared with the DCAG group (15.3 months vs. 9.3 months, P = 0.039). Patients with adverse cytogenetics did benefit from CR. There was no clinically significant additional toxicity observed with the addition of IVC. Conclusion: On the basis of these results, the addition of IVC M low doses to DCAG appeared to improve CR and prolong OS, compared with DCAG, in elderly patients with AML.
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