单倍体造血干细胞移植联合间充质干细胞治疗重型再生障碍性贫血  

Haploidentical Hematopoietic Stem Cell Transplantation with Co-Infusion of Mesenchymal Stromal Cells for Acquired Severe Aplastic Anemia:A Report of 127 Cases

作　　者：韩冬梅 丁丽 郑晓丽 闫洪敏 薛梅 刘静 朱玲 李晟 王恒湘 HAN Dong-Mei;DING Li;ZHENG Xiao-Li;YAN Hong-Min;XUE Mei;LIU Jing;ZHU Ling;LI Sheng;WANG Heng-Xiang(Department of Hematology,Air Force Medical Center,Beijing 100142,China)

机构地区：[1]空军特色医学中心血液科,北京100142

出　　处：《中国实验血液学杂志》2022年第4期1230-1237,共8页Journal of Experimental Hematology

基　　金：首都临床特色应用研究与成果推广(Z151100004015016);首都卫生发展科研专项(首发2014-2-5122)。

摘　　要：目的:分析单倍体造血干细胞移植(haplo-HSCT)联合间充质干细胞治疗重型再生障碍性贫血(SAA)预后的影响因素。方法:回顾性分析2014年1月至2019年8月在空军特色医学中心接受haplo-HSCT联合间充质干细胞输注治疗的SAA患者共127例,中位年龄11(1-37)岁,中位随访时间为39.8(1-74)个月。结果:粒系和血小板的平均植入时间分别为14和18 d。+100 d III-IV度急性移植物抗宿主病(aGVHD)的累积发生率为4.4%±1.9%,2年广泛性慢性移植物抗宿主病(cGVHD)的累积发生率为8.3%±2.7%,3年总体生存(OS)为86.1%±3.1%。单因素分析结果显示:高剂量的CD34+细胞输注(>6.69×106/kg)可以促进粒系(97.9%±0.05%vs 88.6%±0.13%d+21,P=0.0006)和血小板(81.2%±0.33%vs 70.8%±0.26%d+28,P=0.002)的植入而不升高II-IV度aGVHD的发生率(10.4%±0.1%vs 18.9%±0.1%d+100,P=0.18)。高剂量有核细胞输注(>12.78×108/kg)可以提高患者的3年OS(91.3%±3.2%vs 78.1%±6.5%,P=0.03)并减低II–IV度aGVHD的发生率(8.6%±0.13%vs 21.7%±0.25%d+100,P=0.04)。≤12岁的儿童患者粒系植入更快(94.9%±0.06%vs 87.5%±0.24%d+21,P=0.02),3年OS更高(93.6%±2.8%vs 75.9%±6.4%,P=0.006),3年无失败生存(FFS)更高(93.6%±2.8%vs 68.3%±7.1%,P=0.000),发病至移植时间间隔越短(≤29.5个月),患者的3年FFS越高(88.8%±3.5%vs 74.2%±7.2%,P=0.028)。供者为女性的男性患者,广泛性cGVHD的2年累积发生率较其他患者更高(23.3%±2.4%vs 5.4%±2.4%,P=0.01)。结论:在SAA的haplo-HSCT中,儿童患者的预后明显优于成人,输注较多的CD34+细胞及有核细胞可以促进植入、减低aGVHD发生、提高总体生存。SAA患者应尽早行HSCT,男性患者应尽量避免女性供者以减少cGVHD的发生。Objective:To analyze the prognostic factors of haplo-HSCT combined with MSC in the treatment of SAA.Methods:127 SAA patients who had undergone haplo-HSCT with co-infusion of MSC in our center from January 2014 to August 2019 were analyzed retrospectively.Median age was 11(1-37)years,and median follow-up time was 39.8(1-74)months.Results:The median time for neutrophil and platelet engraftment was 14 d and 18 d respectively.The cumulative incidences of grade III-IV aGVHD was 4.4%±1.9%at day+100.The 2-year cumulative incidence of extensive cGVHD was 8.3%±2.7%.The estimated 3-year OS was 86.1%±3.1%.Univariate analysis showed that highdose CD34+cells(>6.69×106/kg)could promote the engraftment of neutrophil(97.9%±0.05%vs 88.6%±0.13%at day+21,P=0.0006)and platelet(81.2%±0.33%vs 70.8%±0.26%at day+28,P=0.002)and did not increase the incidence of aGVHD(10.4%±0.1%vs 18.9%±0.1%at day+100,P=0.18).More nucleated cells(>12.78×108/kg)caused a lower incidence of grade II–IV aGVHD(8.6%±0.13%vs 21.7%±0.25%at day+100,P=0.04)and a higher incidence of 3-year OS(91.3%±3.2%vs 78.1%±6.5%,P=0.03)than less nucleated cells(≤12.78×108/kg).Younger patients(age≤12 y)had faster neutrophil engraftment(94.9%±0.06%vs 87.5%±0.24%at day+21,P=0.02),higher 3-year OS(93.6%±2.8%vs 75.9%±6.4%,P=0.006)and higher 3-year FFS(93.6%±2.8%vs 68.3%±7.1%,P=0.000)than older patients(age>12 y).The shorter the time from diagnosis to HSCT(≤29.5 months),the higher the 3-year FFS of patients(88.8%±3.5%vs 74.2%±7.2%,P=0.028).Male patients with female donors had higher cumulative incidence of extensive cGVHD than others(20.0%±0.8%vs 4.6%±0.1%,P=0.01).Conclusion:In the haplo-HSCT of SAA,the prognosis of children patients is better than that of adults patients.More CD34+cells and nucleated cells can promote engraftment,reduce the incidence of aGVHD and improve OS.HSCT should be performed as early as possible,and the occurrence of cGVHD should be reduced in male patients by avoiding female donors.

关 键 词：重型再生障碍性贫血 单倍体造血干细胞移植 间充质干细胞 

分 类 号：R556.5[医药卫生—血液循环系统疾病]