异基因造血干细胞移植后激素耐药胃肠道急性移植物抗宿主病的临床分析

目的探讨异基因造血干细胞移植后激素耐药胃肠道急性移植物抗宿主病(aGVHD)的影响因素。方法回顾性分析西安交通大学第一附属医院2012年1月至2019年12月期间行异基因造血干细胞移植,术后发生胃肠道aGVHD 20例患者的临床资料。按照一线糖皮质激素治疗后的反应分为激素敏感组(13例)和激素耐药组(7例)。单因素Logistics回归分析患者性别、年龄、诊断、移植前微小残留病灶、移植类型、供者年龄、供受者关系、供受者ABO血型、输注单个核细胞数、CD34+细胞数、CD3+细胞数、中性粒细胞及血小板植入时间、CMV及EB病毒感染、胃肠道aGVHD发生的时间等与激素耐药胃肠道aGVHD的关系。观察激素耐药患者治疗后的转归,采用Kaplan-Meier生存分析激素耐药及敏感患者的预后差异。结果20例胃肠道aGVHD患者中7例存在激素耐药。胃肠道GVHD发生时间<1个月,激素耐药的风险增加(OR=13.500,95﹪CI=1.197~152.211,P=0.035),患者性别、年龄、诊断、移植前MRD、移植类型、供者年龄、供受者关系、供受者ABO血型、输注的单个核细胞、CD34+细胞、CD3+细胞、中性粒细胞和血小板植入时间、CMV和EB病毒感染均不影响激素耐药(P>0.05)。7例激素耐药胃肠道aGVHD患者均接受二线CD25单克隆抗体治疗,治疗后5例有效,2例无效死亡。与激素敏感组比较,激素耐药组患者1年总生存率(64﹪比52﹪)降低及无进展生存率(28﹪比32﹪)升高,差异无统计学意义(P>0.05)。结论异基因造血干细胞移植后胃肠道aGVHD激素耐药可能与其发生时间相关,发生时间越早,越容易出现激素耐药。

Clinical analysis of steroid-resistant acute gastrointestinal graft versus host disease after allogeneic hematopoietic stem cell transplantation

ObjectiveTo explore influence factors of steroid-resistant acute gastrointestinal graft versus host disease (aGVHD) in allogeneic hematopoietic stem cell transplantation. MethodsA retrospective analysis was conducted on 20 patients with aGVHD who underwent allogeneic hematopoietic stem cell transplantation in our hospital from January 2012 to December 2019. Patients were divided into steroid-sensitive group (13 cases) and steroid-resistant group (20 cases) . Patients' gender, age, diagnosis as well as pre-transplant MRD, transplantation type, donor's age, donor-recipient relationship, ABO blood type, mononuclear cell number, CD34⁺ cell number, CD3⁺ cells in graft, neutrophil and platelet engraft time, CMV and EB infection, aGVHD onset time in gastrointestinal tract, of the above factors' relationship with steroid-resistant gastrointestinal aGVHD were analyzed by univariate logistics regression. ResultsAmong 20 patients with gastrointestinal aGVHD, 7 patients were steroid-resistant. When acute GVHD occurs less than 1 month , the risk of steroid resistance was increased (OR = 13.500, 95 ﹪CI = 1.197 ~ 152.211, P = 0.035) . Gender, age, diagnosis, pre-transplant MRD, transplant type, donor age, donor-recipient relationship, donor-recipient ABO blood group, transfused monocytes, CD34⁺ cells, CD3⁺ cells, neutrophils and platelet implantation time, CMV and EB virus infection have no effect in steroid resistance (P > 0.05) . Logistic regression analysis showed that aGVHD onset time in gastrointestinal tract was negatively correlated with steroid-resistant. 7 patients with steroid-resistant gastrointestinal aGVHD were treated with CD25 monoclonal antibody while 2 patients died after ineffective treatment. One year overall survival and progression free survival rates of the steroid-sensitive patients were 64﹪and 28﹪, and one year overall survival and progression free survival rates of the steroid-resistant patients were 52﹪ and 32﹪. There was no significant difference of 1-years OS and PFS between two groups (P > 0.05) . ConclusionSteroid-resistant gastrointestinal aGVHD was related to its onset time after allogeneic hematopoietic stem cell transplantation. The earlier it occurs, the more likely it is to be steroid resistance.