小剂量地西他滨治疗较低危骨髓增生异常综合征患者疗效初步观察  

A preliminary study on the outcome of lower-risk myelodysplastic syndrome by low-dose decitabine

作　　者：叶丽[1] 任艳玲[1] 谢丽丽[1] 罗颖婉[1] 林佩佩[1] 周歆平[1] 马丽亚[1] 梅琛[1] 徐伟来[1] 韦菊英[1] 蒋慧芳[2] 张立明 曾惠[4] 佟红艳[1] 

机构地区：[1]浙江大学医学院附属第一医院血液科骨髓增生异常综合征中心、浙江大学血液病研究所、浙江省血液病重点实验室,杭州310009 [2]浙江省立同德医院血液科 [3]浙江省诸暨市人民医院血液科 [4]浙江省嘉兴市第一医院血液科

出　　处：《中华血液学杂志》2017年第4期307-312,共6页Chinese Journal of Hematology

基　　金：国家自然科学基金（30870914、81270582、81470290）;浙江省科技厅重大项目（2013C03043.2）;浙江省医学会临床科研资金（2015ZYC-A14）

摘　　要：目的评价小剂量地西他滨治疗较低危骨髓增生异常综合征（MDs）患者的初步疗效及安全性，探讨MDS相关基因突变的临床意义。方法纳入浙江省4所医院收治的62例较低危MDS患者，治疗分2组，地西他滨组（地西他滨12mg·m-2·d-1，连续5d）和支持治疗组，检测与MDS预后相关的15项基因突变情况。比较两组患者的总体有效率（oRR）和无进展生存（PFS）时间，分析其与基因突变的相关性。结果62例患者中，可评估患者51例，其中地西他滨组24例，支持治疗组27例。与支持治疗组相比，地西他滨组的ORR（66．7％对29．6％，Z2=6．996，P=0．008）和中位PFS时间显著改善（未达到对13．7个月，P=-0．037）。51例患者中20例（39．2％）检测到基因突变阳性，其中4例患者单纯SF381阳性，均在支持治疗组。与基因突变阴性患者相比，16例基因突变阳性（除单纯SF381阳性）患者中位PFS时间显著缩短（9．2个月对18．5个月，P=-0．008），其中地西他滨组8例患者中6例有效，支持治疗组无一例（0／8）有效。地西他滨治疗期间主要不良反应为3-4级粒细胞减少（45．8％），3~4级感染发生率为33．3％（8／24）。结论该研究小系列患者的初步结果表明应用小剂量地西他滨治疗较低危MDS患者可能有效，对于基因突变患者也可获益，且患者耐受，值得临床试验进一步明确其临床意义。Objective To assess the efficiency and safety of low-dose decitabine in patients with lower-risk myelodysplastic syndrome （MDS） to couple with the clinical significance of MDS-related gene mutations. Methods This study was done in 4 institutions in Zhejiang Province. A total of 62 newly diagnosed patients with lower-risk MDS were assigned to two groups of decitabine （12 mg. m-2. d-1 for 5 consecutive days） and best supportive care （BSC）. Their bone marrow samples were subject to examinations of MDS-related 15 gene mutations. The primary endpoints were the proportion of patients who achieved overall response （ORR） after at least two cycles and progression-free survival （PFS）, and their relevances to the gene mutations. Results Of 62 enrolled patients, and 51 cases were included in the final analysis. 16 of 24 patients （66.7%） in decitabine group achieved ORR versus 8 of 27（29.6%） in BSC group （x2=6.996, P=0.008）; PFS prolongation of decitabine versus BSC was statistically significant （not reached vs 13.7 months, P=0.037）. Among 51 patients, at least one gene mutation was identified in 20 patients （39.2%）, including 4 single SF3B1 mutation. PFS in cases with gene mutations （not includingsingle SF3B1 mutation） was significantly shorter than of no gene mutation （9.2 months vs 18.5 months, P=- 0.008）, but not for ORR （37.5% vs 58.1%, P=0.181）. Among 16 patients with mutated genes, ORR in decitabine and BSC groups were 75%（6/8） and 0（0/8）, respectively. The most adverse events in decitabine group were grade 3 to 4 neutropenia （45.8%） and grade 3 to 4 infections （33.3%）. Conclusion This preliminary study showed that low-dose decitabine produced promising results with an acceptable safety in lower-risk MDS patients, especially for those with mutated genes. Further study targeting poor prognostic lower-risk MDS patients should be warranted.

关 键 词：骨髓增生异常综合征 较低危 地西他滨 低甲基化 

分 类 号：R551.3[医药卫生—血液循环系统疾病]