移植前血清细胞因子水平对重型再生障碍性贫血患者异基因造血干细胞移植疗效的影响研究  

The Effect of Serum Cytokine Levels prior Transplantation on the Outcome of Severe Aplastic Anemia Patients Received Allogeneic Hematopoietic Stem Cell Transplantation

作　　者：王钊[1] 施圆圆[1] 杨欣[1] 张苏东[1] 张利宁[1] 杨栋林[1] 何祎[1] 张荣莉[1] 姜尔烈[1] 魏嘉璘[1] 冯四洲[1] 韩明哲[1] WANG Zhao, SHI Yuan-Yuan, YANG Xin, ZHANG Su-Dong, ZHANG Li-Ning, YANG Dong-Lin, HE Yi, ZHANG Rong-Li, JIANG Er-Lie, WEI Jia-Lin, FENG Si-Zhou, HAN Min-Zhe(Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences ＆ Peking Union Medical College, Tianjin, China. 30002)

机构地区：[1]中国医学科学院北京协和医学院血液学研究所血液病医院,天津300020

出　　处：《中国实验血液学杂志》2018年第2期502-507,共6页Journal of Experimental Hematology

基　　金：中华医学会临床医学科研专项资金(16010130629);中国医学科学院创新工程(2016-12M-1-017)

摘　　要：目的:探讨重型再生障碍性贫血(SAA)患者异基因造血干细胞移植(allo-HSCT)前细胞因子IL-2、IL-6、TNF-α水平对预后的影响。方法:本研究共纳入117例SAA接受allo-HSCT的患者,回顾性分析患者总体生存率(OS)、移植物抗宿主病(GVHD)发生率、细胞因子水平与OS及主要移植并发症的关系。结果:本研究纳入的SAA患者包含同胞HLA全相合allo-HSCT 78例(66.7%),非亲缘供者allo-HSCT 12例(10.2%),单倍体相合供者alloHSCT 27例(23.1%)。所有患者5年OS率为76.0%(95%CI:64.4%-87.5%)。a GVHD累积发生率为49.6%(95%CI:40.4%-58.8%);c GVHD累积发生率为31.6%(95%CI:23.1%-40.2%)。接受同胞HLA全相合allo-HSCT的患者,其5年OS率明显优于替代供者(82.3%±6.6%vs 61.3%±11.7%)(P<0.05)。HLA匹配程度、供者年龄、移植后巨细胞病毒/EB病毒(CMV/EBV)血症是影响a GVHD发生的重要因素。移植前血清IL-6增高的患者,移植后血小板植入较快(14.6±1.8 vs 18.3±2.6 d)(P=0.05);血清TNF-α增高的患者,移植后CMV/EBV血症发生率较低(37.8%±11.1%vs 58.8%±16.8%)(P=0.029)。结论:HLA匹配同胞供者allo-HSCT是SAA患者有效治疗手段;供者选择仍然是影响预后的重要因素。移植前血清IL-6和TNF-α水平增高可能预示allo-HSCT后患者血小板植入加快,CM V/EBV血症发生率减低。Objective： To identify the role of serum cytokine levels prior allogeneic hematopoietic stem cell trans- plantation （allo-HSCT） in the outcome of severe aplastic anemia （SAA） patients received allo-HSCT treatment. Methods： The clinical data of 117 SAA patients received allo-HSCT Were enrolled in this study. The overall survival （OS）, graft versus host disease （GVHD） incidence and relationship of serum cytokines with OS and major transplantation complications were retrospectively analyzed . Results： The patients enrolled in this study included 78 （ 66. 7 % ） cases received HSCT matched sibling donors （ MSD）, 12 （ 10. 2 % ） HSCT of unrelated donors （ MUD ） and 27 cases received HSCT of haploidentical donors （HID）. The 5 - years OS was 76. 0% （95% CI： 64.4 - 87.5% ） ; aGVHD cumulative incidence was 49.6% （95% CI： 40. 4% -58.8% ）and cumulative incidence cGVHD was 31.6% （95% CI：23.1% -40.2% ）. MSD allo-HSCT had a significantly higher 5 -years OS as compared with the other donors（82. 3%±6. 6% vs 61.3%±11.7%, P 〈0.05）. HLA matching, donor＇s age, cytomegalovirus/ Epstein-Barr virus （CMV/EBV） infection were important factors of affecting occurence of aGVHD. The patients with higher serum IL-6 had reduced platelet recovery time after transplantation （ 14. 6±1.8 vs 18.3±2. 6 d） （P =0. 050 ） and higher serum TNF-a level accompanied by a lower incidence of CMV/EBV infection （37.8% ±11. 1% vs 58.8±16. 8% ） （P 〈 0. 05 ）. Conclusion： MSD allo-HSCT is the effective treatment for SAA patients. Donor＇s type remains the strong predictor of survival. The serum levels IL-6 and TNF-α before transplantation associate with platelet recovery and CMV/ EBV infection.

关 键 词：再生障碍性贫血 造血干细胞移植 血清细胞因子 移植物抗宿主病 

分 类 号：R556.5[医药卫生—血液循环系统疾病] R457.7[医药卫生—内科学]