供者特异性HLA抗体及去敏治疗对单倍体造血干细胞移植植入效果的影响  

Effects of anti-HLA donor-specific antibodies and desensitization on engraftment of haploidentical hematopoietic stem cell transplantation

作　　者：马遥 张艳芳 周慷[1] 罗云[1] 陈姝[1] 娄世锋[1] 邓建川[1] MA Yao;ZHANG Yanfang;ZHOU Kang;LUO Yun;CHEN Shu;LOU Shifeng;DENG Jianchuan(Department of Hematology,the Second Affiliated Hospital of Chongqing Medical University,Chongqing,400010,China)

机构地区：[1]重庆医科大学附属第二医院血液内科,重庆400010

出　　处：《陆军军医大学学报》2024年第4期319-325,共7页Journal of Army Medical University

摘　　要：目的 分析供者特异性HLA抗体(anti-HLA donor-specific antibodies, DSA)及DSA阳性患者的去敏治疗对单倍体造血干细胞移植(haploidentical hematopoietic stem cell transplantation, haplo-HSCT)植入效果的影响。方法 收集2017年3月至2023年7月重庆医科大学附属第二医院血液内科行haplo-HSCT,并完成HLA抗体及DSA检测的患者70例,分析DSA阳性和DSA阳性患者去敏治疗对造血干细胞移植植入效果的影响。结果 70例haplo-HSCT患者完成抗体检测,DSA阳性患者15例(21.4%),其中7例(46.7%)强阳性,3例(20.0%)中度阳性,5例(33.3%)弱阳性。DSA阳性患者移植后粒系植入中位时间较DSA阴性患者明显延迟(P=0.027)。植入失败(graft failure, GF)患者6例,DSA阳性4例(26.7%),明显高于DSA阴性(P=0.025)。多因素分析结果显示,DSA是发生GF的独立影响因素(HR=9.273, 95%CI=1.505~57.124,P=0.016)。10例DSA中度和强阳性患者进行去敏治疗,4例采用联合去敏治疗,患者均成功植入(100.0%),6例采用单一去敏治疗,有4例(66.7%)发生GF,联合去敏治疗的GF发生率显著低于单一去敏治疗(P=0.008)。结论 DSA是导致haplo-HSCT患者植入延迟和GF的重要因素,对DSA中度及强阳性患者的单一去敏治疗效果有限,而多联合的去敏治疗时,动态监测抗体滴度水平下降,可保证干细胞的成功植入,降低GF发生。Objective To investigate the effects of anti-HLA donor-specific antibodies(DSA)and desensitization for DSA+patients on engraftment of haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods The patients who underwent haplo-HSCT and examinations for HLA antibodies and DSA in our department from March 2017 to July 2023 were recruited in this study.The effects of desensitization measure on engraftment in the DSA+patients after haplo-HSCT were analyzed.Results Among the 70 patients who underwent haplo-HSCT and test for HLA antibodies,15(21.4%)patients were DSA positive,including 7(46.7%)cases of strong positive,3(20.0%)cases of moderate positive,and 5(33.3%)cases of weak positive.The median duration for neutrophil implantation was significantly extended in the DSA+patients than the negative patients(P=0.027).For the 6 patients developed graft failure(GF),4 were DSA+which was statistically higher than the DSA-patients(P=0.025).Multivariate regression analysis showed that DSA was an independent factor affecting GF(HR=9.273,95%CI:1.505~57.124,P=0.016).Among the 10 patients(7 strong positive and 3 moderate positive DSA)received desensitization therapy,4 patients received combination desensitization,with a 100%rate of successful transplantation,and 6 received single desensitization,with 4(66.7%)experiencing GF,so the GF rate was obviously lower in the combination than the single desensitization(P=0.008).Conclusion In haplo-HSCT patients,DSA is an important factor leading to implantation delay and GF.While,single desensitization treatment has limited efficacy.In combined DSA desensitization therapy,the decrease of antibody titer should be dynamically monitored to ensure the successful implantation of stem cells and reduce GF rate.

关 键 词：供者特异性HLA抗体 单倍体造血干细胞移植 植入失败 去敏治疗 

分 类 号：R195.4[医药卫生—卫生统计学] R394.1[医药卫生—卫生事业管理] R736.6[医药卫生—公共卫生与预防医学]