CD8^(+)CD28^(-)T细胞对单倍型造血干细胞移植后急性移植物抗宿主病的影响  

Effect of CD8^(+)CD28^(-)T Cells on Acute Graft-Versus-Host Disease after Haploidentical Hematopoietic Stem Cell Transplantation

作　　者：张安迪 魏筱萱 郭佳媛 金香淑 张琳琳 李菲 谷振阳 薄剑 窦立萍 刘代红 李猛 高春记 ZHANG An-Di;WEI Xiao-Xuan;GUO Jia-Yuan;JIN Xiang-Shu;ZHANG Lin-Lin;LI Fei;GU ZHEN-Yang;BO Jian;DOU Li-Ping;LIU Dai-Hong;LI Meng;GAO Chun-Ji(Medical School of Chinese PLA,Beijing 100853,China;Department of Hematology,The Fifth Medical Center,Chinese PLA General Hospital,Beijing 100071,China;School of Medicine,Nankai University,Tianjin 300071,China)

机构地区：[1]解放军医学院,北京100853 [2]中国人民解放军总医院第五医学中心血液病医学部,北京100071 [3]南开大学,天津300071

出　　处：《中国实验血液学杂志》2024年第3期896-905,共10页Journal of Experimental Hematology

摘　　要：目的:探讨CD8^(+)CD28^(-)T细胞对单倍型造血干细胞移植(haplo-HSCT)后急性移植物抗宿主病(aGVHD)的影响。方法:回顾性分析60例行haplo-HSCT的血液病患者移植后CD8^(+)CD28^(-)T细胞绝对计数与aGVHD的关系,并比较不同CD8^(+)CD28^(-)T细胞绝对计数组间慢性移植物抗宿主病(cGVHD)、感染及预后的差异。结果:60例行haplo-HSCT患者中有40例发生aGVHD,发生率为66.67%,中位发生时间为32.5(20-100)天。Haplo-HSCT后30天,aGVHD组CD8^(+)CD28^(-)T细胞绝对计数显著低于无aGVHD组(P=0.03)。ROC曲线表明移植后30天CD8^(+)CD28^(-)T细胞绝对计数在一定程度上可预测aGVHD的易感性。移植后30天低细胞计数组(CD8^(+)CD28^(-)T细胞绝对计数<0.06/μl)患者的aGVHD发生率显著高于高细胞计数组(CD8^(+)CD28^(-)T细胞绝对计数≥0.06/μl,P=0.011)。多因素Cox回归分析进一步验证了移植后30天CD8^(+)CD28^(-)T细胞绝对计数是aGVHD发生的独立风险因素,低细胞计数组aGVHD的发生风险是高细胞计数组的2.222倍(P=0.015)。不同CD8^(+)CD28^(-)T细胞绝对计数组间cGVHD、真菌感染、EB病毒感染、巨细胞病毒感染的发生无统计学差异。不同CD8^(+)CD28^(-)T细胞绝对计数组的总生存率、非复发相关死亡率、复发率没有显示出明显的统计学差异。结论:行haplo-HSCT后30天CD8^(+)CD28^(-)T细胞延迟重建的患者更易发生aGVHD,并且CD8^(+)CD28^(-)T细胞绝对计数在一定程度上可预测其易感性。单倍型造血干细胞移植后CD8^(+)CD28^(-)T细胞绝对计数与cGVHD、真菌感染、EB病毒感染、巨细胞病毒感染无关,且与移植后的生存预后无显著相关。Objective:To investigate the effect of CD8^(+)CD28^(-)T cells on acute graft-versus-host disease(aGVHD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods:The relationship between absolute count of CD8^(+)CD28^(-)T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT,and the differences in the incidence rate of chronic graft-versus host disease(cGVHD),infection and prognosis between different CD8^(+)CD28^(-)T absolute cells count groups were compared.Results:aGVHD occurred in 40 of 60 patients after haplo-HSCT,with an incidence rate of 66.67%.The median occurrence time of aGVHD was 32.5(20-100)days.At 30 days after the transplantation,the absolute count of CD8^(+)CD28^(-)T cells of aGVHD group was significantly lower than that of non-aGVHD group(P=0.03).Thus the absolute count of CD8^(+)CD28^(-)T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent.At 30 days after transplantation,the incidence rate of aGVHD in the low cell count group(CD8^(+)CD28^(-)T cells absolute count<0.06/μl)was significantly higher than that in the high cell count group(CD8^(+)CD28^(-)T cells absolute count≥0.06/μl,P=0.011).Multivariate Cox regression analysis further confirmed that the absolute count of CD8^(+)CD28^(-)T cells at 30 days after transplantation was an independent risk factor for aGVHD,and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group(P=0.015).The incidence of cGVHD,fungal infection,EBV infection and CMV infection were not significantly different between the two groups with different CD8^(+)CD28^(-)T cells absolute count.The overall survival,non-recurrent mortality and relapse rates were not significantly different between different CD8^(+)CD28^(-)T cells absolute count groups.Conclusion:Patients with delayed CD8^(+)CD28^(-)T cells reconstitution after haplo-HSCT are more likely to develop aGVHD,and the absolute count of CD8

关 键 词：CD8^(+)CD28^(-)T细胞 单倍型造血干细胞移植 急性移植物抗宿主病 

分 类 号：R457.7[医药卫生—治疗学]