地西他滨联合亚砷酸诱导治疗中高危骨髓增生异常综合征及慢性粒单核细胞白血病47例临床研究  

Decitabine combined with arsenious acid in the treatment of patients with higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia

作　　者：陆星羽 吴雪梅[1,2] 吴文忠[3] 李炳宗[2] 林芸[4] 张新龙[5] 沈云峰[6] 周新[6] 卢旭章[7] 朱彦 师锦宁[9] 高华强 徐敏[11] 谢晓宝[12] 何广胜[1] 李建勇[1] LU Xing-yu;WU Xue-mei;WU Wen-zhong;LI Bing-zong;LIN Yun;ZHANG Xin-long;SIIEN Yun-feng;ZHOU Xin;LU Xu-zhang;ZHU Yan;SHI Jin-ning;GAO Hua-qiang;XU Min;XIE Xiao-bao;HE Guang-sheng;LI Jian-yong(Department ofHematology, the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing 210029, China)

机构地区：[1]南京医科大学第一附属医院江苏省人民医院血液科,江苏南京210029 [2]苏州大学附属第二医院,江苏苏州215000 [3]宜兴市人民医院,江苏宜兴214200 [4]福建省立医院,福建福州350000 [5]丹阳市人民医院,江苏丹阳212300 [6]南京医科大学附属无锡市人民医院,江苏无锡214000 [7]南京医科大学附属常州市第二人民医院,江苏常州213000 [8]江苏大学附属医院,江苏镇江212000 [9]南京医科大学附属江宁医院,江苏南京211100 [10]无锡市第三人民医院,江苏无锡214000 [11]张家港市第一人民医院,江苏张家港215600 [12]常州市第一人民医院,江苏常州213000

出　　处：《中国实用内科杂志》2019年第5期452-455,共4页Chinese Journal of Practical Internal Medicine

基　　金：国家科技攻关项目(2014BAI09B12);卫生部科研基金(201202017);江苏省医学重点项目(BL2014086);江苏省普通高校优势学科(JX10231801)

摘　　要：目的探讨地西他滨联合亚砷酸方案诱导治疗中高危骨髓增生异常综合征(MDS)及慢性粒单核细胞白血病(CMML)的临床疗效。方法收集2016年4月至2018年12月中国贫血东部协作组接受地西他滨联合亚砷酸治疗的中高危MDS患者39例及CMML患者8例。地西他滨20 mg/(m^2·d)联合亚砷酸0.15 mg/(m^2·d),治疗5 d,4～6周1个疗程,完全缓解(CR)或部分缓解(PR)者进入巩固周期,分析疗效及影响因素。结果中位疗程为2个疗程(1～12个疗程),31例(66.0%)获得了临床反应,中位疗效持续时间16周(2～52周)。CR 8例(17.0%),PR 10例(21.3%),血液学改善12例(25.5%),骨髓CR 1例(2.1%),疾病稳定8例(17.0%),疾病进展1例(2.1%)。二代测序基因检测中,33例发现25个基因突变70次。表观遗传学基因突变率(57.6%)高于剪接子复合物(33.5%)、转录因子和激酶系统(54.5%)和TP53组(21.2%),差异有统计学意义(P<0.01),但疗效差异无统计学意义(分别为47.4%、54.5%、50.0%和85.7%,P=0.977)。治疗有效患者等位基因突变频率(VAF)显著下降(16.67%对10.26%,P=0.014)。结论地西他滨联合亚砷酸方案诱导治疗中高危MDS及CMML的疗效佳,且不良反应少。二代基因突变检测结果可能与疗效反应有关。Objective To evaluate the clinical efficacy of decitabine combined with arsenious acid in the treatment of patients with higher-risk myelodysplastic syndromes(MDS) and chronic myelomonocytic leukemia(CMML). Methods Totally 39 patients with MDS and 8 patients with CMML received the treatment of decitabine and arsenious acid from April 2016 to December 2018. Decitabine [20 mg/(m^2·d)] and arsenious acid [0.15 mg/(m^2·d)] were administered intravenously for 5 consecutive days every 4-6 weeks. Patients who achieved complete or partial remission entered into the consolidation cycle. Efficacy and influencing factor were analyzed. Results Clinical response were observed in 31 patients after a median of 2 courses(ranging 1-12) of treatment. The overall response rate(ORR) was 66.0%. The median duration of response was 16 weeks(ranging 2-52 weeks). There were 8 cases(17.0%) of complete remission(CR), 10 cases(21.3%) of partial remission(PR),12 cases(25.5%) of hematological improvement(HI), 1 case(2.1%) of marrow complete remission(mCR), 8 cases(17.0%) of stable disease(SD), and 1 case(2.1%) of progressive disease(PD). By next generation sequencing, 25 genes mutated with 70 times in 33 cases. The mutation frequency of epigenetic regulators(57.6%) was higher than splicing factors(33.5%), transcription factors and kinase signaling(54.5%),and TP53(21.2%)(P<0.01). There was no significant difference in response rates among these patients(47.4%, 54.5%, 50.0% and85.7%, P=0.977). Gene mutation frequency(VAF) of patients who responded to the regimen declined significantly(16.67% vs. 10.26%,P=0.014). Conclusion Decitabine combined with arsenious acid has significant effect in the treatment of patients with higher-risk MDS and CMML and is well-tolerated. Gene mutation test results by next generation sequencing might be related to clinical response.

关 键 词：骨髓增生异常综合征 慢性粒单核细胞白血病 中高危 地西他滨 亚砷酸 

分 类 号：R551.3[医药卫生—血液循环系统疾病]