期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 167, 期 5, 页码 664-670出版社
WILEY-BLACKWELL
DOI: 10.1111/bjh.13094
关键词
acute myeloid leukaemia; myelodysplastic syndrome; chemotherapy; temozolomide; drug resistance
类别
资金
- Merck Canada
Resistance to temozolomide is largely mediated by the DNA repair enzyme O-6-methylguanine DNA methyltransferase (MGMT). We conducted a prospective multicentre study of patients with previously untreated acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) who were not candidates for intensive therapy. Patient selection was based on MGMT expression by Western blot. Patients with MGMT: ACTB (beta-actin) ratio <0.2 were eligible to receive temozolomide 200 mg/m(2)/d x7 d. Patients achieving a complete response (CR) could receive up to 12 monthly cycles of temozolomide x5/28 d. Of 166 patients screened, 81 (49%) demonstrated low MGMT expression; 45 of these were treated with temozolomide. The overall response rate was 53%; 36% achieved complete clearance of blasts, with 27% achieving a CR/CR with incomplete platelet recovery (CRp). Factors associated with a trend toward a higher response rate included MDS, methylated MGMT promoter and standard cytogenetic risk group. Induction and post-remission cycles were well-tolerated and most patients were treated on an outpatient basis. Patient who achieved CR/CRp had a superior overall survival compared to partial or non-responders. In conclusion, targeted therapy based on pre-selection for low MGMT expression was associated with a higher response rate to temozolomide compared to previous reports of unselected patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据