足疗程去甲基化药物治疗骨髓增生异常综合征:多中心回顾性研究  

Long-term hypomethylating agents in patients with myelodysplastic syndromes:a multi-center retrospective study

作　　者：刘晓珍 周淑娟[2] 黄健[1,3] 赵彩芳 蒋灵旭[1] 张喻堤 梅琛 马丽亚[1] 周歆平[1] 邵燕萍[5] 吴功强[6] 肖希斌 姚荣欣[8] 杜小红[9] 胡通林 钱申贤[11] 李园[12] 严雪芬 黄黎 王曼玲[15] 傅佳萍[16] 寿黎红[17] 江文华[18] 金伟媚[19] 李琳洁 乐静[21] 罗文纪[22] 张蕴[23] 周秀杰 张浩[25] 郎香花[26] 周梅 金洁 蒋慧芳[28] 张瑾[29] 欧阳桂芳 佟红艳[1] Liu Xiaozhen;Zhou Shujuan;Huang Jian;Zhao Caifang;Jiang Lingxu;Zhang Yudi;Mei Chen;Ma Liya;Zhou Xinping;Shao Yanping;Wu Gongqiang;Xiao Xibin;Yao Rongxin;Du Xiaohong;Hu Tonglin;Qian Shenxian;Li Yuan;Yan Xuefen;Huang Li;Wang Manling;Fu Jiaping;Shou Lihong;Jiang Wenhua;Jin Weimei;Li Linjie;Le Jing;Luo Wenji;Zhang Yun;Zhou Xiujie;Zhang Hao;Lang Xianghua;Zhou Mei;Jin Jie;Jiang Huifang;Zhang Jin;Ouyang Guifang;Tong Hongyan(Department of Hematology,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;Department of Hematology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China;Department of Hematology,the Fourth Affiliated Hospital,Zhejiang University School of Medicine,Yiwu 322000,China;Department of Hematology,Jinhua Municipal Central Hospital,Jinhua 321000,China;Department of Hematology,Taizhou Hospital,Taizhou 317000,China;Department of Hematology,Dongyang Hospital Affiliated to Wenzhou Medical University,Dongyang 322100,China;Department of Hematology,Zhejiang University School of Medicine Second Affiliated Hospital,Hangzhou 310009,China;Department of Hematology,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325035,China;Department of Hematology,Ningbo Yinzhou People's Hospital,Ningbo 315040,China;Department of Hematology,Zhejiang Provincial Hospital of TCM,Hangzhou 310006,China;Department of Hematology,Hangzhou First People's Hospital,Hangzhou 310006,China;Department of Hematology,First Hospital of Jiaxing,Jiaxing 314001,China;Department of Hematology,Quzhou People's Hospital,Quzhou 324000,China;Department of Hematology,Jinhua People's Hospital,Jinhua 321000,China;Department of Hematology,Zhejiang Provincial People's Hospital,Hangzhou 310014,China;Department of Hematology,Shaoxing People's Hospital,Shaoxing 312000,China;Department of Hematology,Huzhou Central Hospital,Huzhou 313000,China;Department of Hematology,Taizhou First People's Hospital,Taizhou 318020,China;Department of Hematology,Lishui Municipal People Hospital,Lishui

机构地区：[1]浙江大学医学院附属第一医院血液科,杭州310003 [2]温州医科大学附属第一医院血液科,温州325015 [3]浙江大学医学院附属第四医院血液科,义乌322000 [4]金华市中心医院血液科,金华321000 [5]浙江省台州医院血液科,台州317000 [6]东阳市人民医院血液科,东阳322100 [7]浙江大学医学院附属第二医院血液科,杭州310009 [8]温州医科大学附属第二医院血液科,温州325035 [9]宁波市鄞州人民医院血液科,宁波315040 [10]浙江省中医院血液科,杭州310006 [11]杭州市第一人民医院血液科,杭州310006 [12]嘉兴市第一医院血液科,嘉兴314001 [13]衢州市人民医院血液科,衢州324000 [14]金华市人民医院血液科,金华321000 [15]浙江省人民医院血液科,杭州310014 [16]绍兴市人民医院血液科,绍兴312000 [17]湖州市中心医院血液科,湖州313000 [18]台州市第一人民医院血液科,台州318020 [19]丽水市人民医院血液科,丽水323000 [20]丽水市中心医院血液科,丽水323000 [21]宁波市医疗中心李惠利医院血液科,宁波315040 [22]杭州市萧山区第一人民医院血液科,杭州311200 [23]乐清市人民医院血液科,乐清325600 [24]海宁市人民医院血液科,海宁314400 [25]瑞安市人民医院血液科,瑞安325200 [26]永康市第一人民医院血液科,永康321300 [27]诸暨市人民医院血液科,诸暨311800 [28]浙江省立同德医院血液科,杭州310012 [29]浙江大学医学院附属邵逸夫医院血液科,杭州310016 [30]宁波大学附属第一医院血液科,宁波315010

出　　处：《中华血液学杂志》2024年第8期738-747,共10页Chinese Journal of Hematology

基　　金：国家自然科学基金(82270146)。

摘　　要：目的研究去甲基化药物(HMA)足疗程治疗骨髓增生异常综合征(MDS)的疗效和安全性。方法纳入来自浙江省45家医院的409例接受了至少连续4个周期的HMA单药起始治疗的MDS患者,评估HMA疗效和安全性。采用Mann-Whitney U或卡方检验比较组间临床资料差异,采用Logistic回归和Cox回归分析疗效与生存的影响因素,采用Kaplan-Meier法进行生存分析。结果409例患者HMA治疗的中位疗程为6(4~25)个疗程。完全缓解(CR)率为33.98%,总缓解率(ORR)为77.02%。多因素分析显示,复杂核型(P=0.02,OR=0.39,95%CI 0.18~0.84)是CR的独立良好影响因素;TP53突变(P=0.02,OR=0.22,95%CI 0.06~0.77)是ORR的独立良好预测因素。患者的中位总生存(OS)时间为25.67(95%CI 21.14~30.19)个月,HMA治疗有反应(P=0.036,HR=0.47,95%CI 0.23~0.95)是OS的独立良好预后因素,而伴有复杂核型(P=0.024,HR=2.14,95%CI 1.10~4.15)、发生白血病转化(P<0.001,HR=2.84,95%CI 1.64~4.92)、TP53突变(P=0.012,HR=2.19,95%CI 1.19~4.07)均是OS的独立不良预后因素。HMA减剂量较标准剂量在疗效和中位OS时间均无显著差异。地西他滨和阿扎胞苷治疗组的CR率、ORR均无显著差异。接受地西他滨治疗患者的中位OS时间长于接受阿扎胞苷治疗患者(29.53个月对20.17个月,P=0.007),但地西他滨组严重骨髓抑制、肺炎发生率高于阿扎胞苷组。结论在患者能够耐受情况下,连续规律地使用适当剂量的HMA,有利于MDS患者最大程度从治疗中获益。Objective To evaluate the efficacy and safety of hypomethylating agents(HMA)in patients with myelodysplastic syndromes(MDS).Methods A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA.Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data.Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival.Kaplan-Meier was used for survival analysis.Results Patients received HMA treatment for a median of 6 cycles(range,4-25 cycles).The complete remission(CR)rate was 33.98%and the overall response rate(ORR)was 77.02%.Multivariate analysis revealed that complex karyotype(P=0.02,OR=0.39,95%CI 0.18-0.84)was an independent favorable factor for CR rate.TP53 mutation(P=0.02,OR=0.22,95%CI 0.06-0.77)was a predictive factor for a higher ORR.The median OS for the HMA-treated patients was 25.67(95%CI 21.14-30.19)months.HMA response(P=0.036,HR=0.47,95%CI 0.23-0.95)was an independent favorable prognostic factor,whereas complex karyotype(P=0.024,HR=2.14,95%CI 1.10-4.15),leukemia transformation(P<0.001,HR=2.839,95%CI 1.64-4.92),and TP53 mutation(P=0.012,HR=2.19,95%CI 1.19-4.07)were independent adverse prognostic factors.There was no significant difference in efficacy and survival between the reduced and standard doses of HMA.The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different.The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine(29.53 months vs 20.17 months,P=0.007).The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group.Conclusion Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

关 键 词：骨髓增生异常综合征 去甲基化药物 地西他滨 阿扎胞苷 预后 

分 类 号：R551.3[医药卫生—血液循环系统疾病]