地西他滨治疗骨髓增生异常综合征的临床疗效及P15甲基化变化研究

Curative effect of decitabine for myelodsyplastic syndrome and the methylation change of P15 gene

目的分析地西他滨治疗骨髓增生异常综合征（MDS）患者的临床疗效与不良反应,并探讨治疗后P15基因的甲基化水平变化。方法对广东省人民医院血液科2009年11月至2012年3月接受地西他滨治疗的31例MDS患者[难治性血细胞减少伴多系病态造血（RCMD）9例,难治性贫血伴有原始细胞增多I（RAEB-Ⅰ）11例,RAEB-Ⅱ7例,慢性粒单核细胞白血病（CMML）4例]进行回顾性分析,其中28例接受5 d方案,3例接受3 d方案。从中抽取7例RAEB-Ⅰ及RAEB-Ⅱ患者,使用实时荧光定量聚合酶链式反应（PCR）连续监测其P15基因甲基化水平的变化。结果在可评估的28例患者中,完全缓解（CR）3例,骨髓完全缓解伴血液学改善（m CR＋HI）5例,骨髓完全缓解（m CR）7例,单纯血液学改善（HI）3例,疾病稳定（SD）9例,疾病进展1例,CR率10.7%,总有效率（CR＋m CR＋HI）64.3%,2年生存率为46.4%。经地西他滨治疗后,患者P15基因明显降低,且用药后第1周下降幅度最大,达20%~60%。结论地西他滨治疗MDS患者具有一定疗效,不良事件具有可控性,且治疗后P15基因明显下降。

Objective To evaluate the curative effectiveness and side effects of decitabine in the treatment of myelodyspastic syndrome （MDS）, and also to explore the relationship between the methylation level of P15 gene and clinical features in this retrospective study. Methods Thirty-one MDS patients, including 9 cases of refractory cytopenia with multilineage dysplasia （RCMD）, 11 cases of refractory anemia with excess blast-I （RAEB- I ）, 7 cases of RAEB- lI and 4 cases of chronic myelomonocytic leukaemia （CMML）, treated with decitabine were enrolled in this study. Among them, there were 28 patients treated based on 5-day schedule and 3 patients received 3-day schedule. Seven patients with RAEB- ｜ / H were selected and the peripheral blood were collected. Quantitative real-time polymerase chain reaction （PCR） was performed to detect the methylation level of P 15 gene. Results Among the assessable 28 cases, there were 3 cases gained complete remission （CR）, 5 cases obtained bone marrow complete remission with hematological improvement （mCR＋HI）, 7 cases with bone marrow complete remission （mCR）, 3 patients with simple hematologic improvement （HI）, 9 cases with stable disease （SD） and 1 case experiencing disease progression. The CR rate was 10.7% and total effective rate （CR ＋ mCR ＋ HI） was up to 64.3%, while the 2-year survival rate was 46.4%. Importantly, decitabine treatment significantly reduced P15 gene methylation in patients, with the peak of reduction about 20%-60% appeared in the first week. Conclusion Decitabine appears to be effective for the treatment of MDS and the efficacy is possibly mediated by reducing the methylation of P 15 gene.