恶性血液病单倍型造血干细胞移植预处理中兔抗人胸腺细胞球蛋白剂量优化探讨  

Optimization of ATG dose in haploid hematopoietic stem cell transplantation for hematologic malignancies

作　　者：周茜[1] 陆铉 唐亮 严晗 陈文兰 石威 仲照东 游泳[1] 夏凌辉[1] 胡豫[1] 王华芳[1] Zhou Xi;Lu Xuan;Tang Liang;Yan Han;Chen Wenlan;Shi Wei;Zhong Zhaodong;You Yong;Xia Linghui;Hu Yu;Wang Huafang(Institute of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)

机构地区：[1]华中科技大学同济医学院附属协和医院血液病研究所,武汉430022

出　　处：《中华血液学杂志》2020年第7期557-563,共7页Chinese Journal of Hematology

摘　　要：目的:比较含不同剂量兔抗人胸腺细胞球蛋白(rATG)预处理方案单倍型造血干细胞移植(haplo-HSCT)对恶性血液病患者的疗效。方法:对2013年3月至2018年12月行haplo-HSCT的恶性血液病患者进行回顾性分析,按预处理方案中rATG总量6、7.5、9 mg/kg分为ATG-6、ATG-7.5、ATG-9三组,比较三组患者急性移植物抗宿主病(GVHD)发生率、感染发生率及生存率。结果:①纳入288例患者,男182例,女106例,中位年龄18(6~62)岁。急性髓系白血病(AML)128例,急性淋巴细胞白血病(ALL)110例,慢性髓性白血病(CML)8例,骨髓增生异常综合征(MDS)28例,混合细胞白血病(MAL)14例。ATG-6组159例,ATG-7.5组72例,ATG-9组57例。移植后中位随访时间为14.0(0.2~74.0)个月。②ATG-6、ATG-7.5、ATG-9组粒细胞植入率分别为96.9%、97.2%、96.5%(P=0.972),血小板植入率分别为92.5%、87.5%、86.0%(P=0.276),Ⅱ~Ⅳ度急性GVHD发生率分别为14.5%、11.1%、8.8%(P=0.493),慢性GVHD发生率分别为8.8%、14.3%、12.0%(P=0.493)。ATG-9组的CMV、EBV感染率(77.2%、12.5%)均高于ATG-6组(43.3%、3.5%)和ATG-7.5组(44.4%、1.5%)(P<0.001,P=0.033)。③ATG-6、ATG-7.5、ATG-9组移植后3年总生存率分别为68.5%(95%CI 60.3%~77.9%)、60.1%(95%CI 48.3%~74.8%)、64.7%(95%CI 51.9%~80.7%)(P=0.648),3年累积复发率分别为34.6%(95%CI 34.3%~35.1%)、38.0%(95%CI 37.3%~38.7%)、20.6%(95%CI 20.0%~21.3%)(P=0.165),3年无病生存率分别为53.3%(95%CI 44.9%~63.4%)、51.9%(95%CI 41.0%~65.8%)、63.9%(95%CI 51.9%~78.7%)(P=0.486),3年非复发死亡率分别为24.2%(95%CI 23.8%~24.5%)、26.0%(95%CI 25.4%~26.6%)、23.6%(95%CI 26.3%~28.2%)(P=0.955)。结论:低剂量rATG(6 mg/kg)可增加haplo-HSCT后Ⅱ~Ⅳ度急性GVHD的发生率,高剂量rATG(9 mg/kg)使CMV、EBV感染风险增加,中剂量ATG(7.5 mg/kg)可能是兼顾降低中重度急性GVHD和CBV/EBV感染发生率的选择。Objective To compare the clinical efficacy of different doses of rabbit antithymocyte globulin(rATG)in haplo-HSCT in the treatment of hematologic malignancies.Methods Malignant hematological patients treated at our hospital from March 2013 to December 2018 were retrospectively analyzed.These patients were divided into three groups as per three doses of ATG(6 mg/kg,7.5 mg/kg,and 9 mg/kg)in the conditioning regimens.The transplant outcomes were compared in terms of the occurrence of acute graft versus host disease(GVHD),infection,and survival.Results①Total 288 patients were enrolled in the study,including 182 men and 106 women,with a median age of 18(6-62)years.Total 110 patients were diagnosed with acute lymphoblastic leukemia(ALL),128 with acute myelogenous leukemia(AML),8 with chronic myeloid leukemia(CML),28 with myelodysplastic syndrome(MDS),and 14 with mixed cell leukemia(MAL).There were 159 patients in the ATG-6 group,72 in the ATG-7.5 group,and 57 in the ATG-9 group.The median follow-up time of post transplantation was 14(0.2-74)months.②The incidence of neutrophil engraftment(96.9%,97.2%,and 96.5%,respectively)and platelet engraftment(92.5%,87.5%,and 86%,respectively)did not significantly differ among the ATG-6,ATG-7.5,and ATG-9 groups(P=0.972,P=0.276).The incidence of grades 2-4 acute GVHD was 14.5%,11.1%,and 8.8%in the three groups,respectively(P=0.493),chronic GVHD incidence in the three group was 8.8%,14.3%and 12.0%,respectively(P=0.493).The infection rates of CMV and EBV in the ATG-9 group(77.2%and 12.5%)were significantly higher than those in the ATG-6(43.3%and 3.5%),and ATG-7.5 group(44.4%and 1.5%)(P<0.001 and P=0.033,respectively).③Among the three groups,there were no significant difference in the 3-year overall survival[68.5%(95%CI 60.3%-77.9%),60.1%(95%CI 48.3%-74.8%),64.7%(95%CI 51.9%-80.7%)],cumulative incidences of relapse[34.6%(95%CI 34.3%-35.1%),38.0%(95%CI 37.3%-38.7%),20.6%(95%CI 20.0%-21.3%)],disease-free survival[53.3%(95%CI 44.9%-63.4%),51.9%(95%CI 41%-65.8%),63.9%(95%CI 51.9%-78.7

关 键 词：单倍型造血干细胞移植 抗胸腺细胞球蛋白 移植物抗宿主病 预后 

分 类 号：R457.7[医药卫生—治疗学]