摘要
背景:提出单倍型异基因造血干细胞移植后高剂量环磷酰胺诱导免疫耐受的新技术,理论与实践相结合,优化造血干细胞移植治疗儿童重型再生障碍性贫血的技术体系,为临床推广应用提供理论基础。目的:探讨单倍型异基因造血干细胞移植后应用大剂量环磷酰胺诱导免疫耐受治疗儿童重型再生障碍性贫血的临床疗效和安全性。方法:解放军北京军区总医院血液科2013年1月至2015年1月应用单倍型异基因造血干细胞移植治疗10例重型再生障碍性贫血患儿(治疗组),预处理方案为环磷酰胺、氟达拉滨、白舒非联合抗人淋巴细胞免疫球蛋白,移植后+3 d用环磷酰胺(50 mg/kg·d)诱导免疫耐受,供者接受粒细胞集落刺激因子动员,采用骨髓联合外周血干细胞移植。移植物抗宿主病预防采用环孢素A、氨甲蝶呤、他克莫司等联合免疫抑制剂。选择同期行全相合造血干细胞移植治疗10例重型再生障碍性贫血患儿为对照组,统计两组患儿移植相关并发症及存活情况。结果与结论:随访至2015年5月,治疗组中位随访时间18.1个月(5-28个月),全部患儿均获造血重建,3例发生移植物抗宿主病、3例合并肺部感染,肺部感染死亡2例;对照组中位随访时间20.7个月(6-27个月),全部患儿均获造血重建,2例发生移植物抗宿主病、4例合并肺部感染,移植物抗宿主病死亡1例、肺部感染死亡1例,两组患儿总生存率均为80%。结果表明单倍型异基因造血干细胞移植后大剂量环磷酰胺诱导免疫耐受治疗儿童重型再生障碍性贫血安全有效,临床疗效与全相合造血干细胞移植相当。
BACKGROUND： High-dose cyclophosphamide（CTX）-induced immunogenic tolerance following haploidentical allogeneic hematopoietic stem cell transplantation（allo-HSCT） is developed to optimize the treatment of childhood severe aplastic anemia（SAA） using haplotype allo-HSCT, providing a theoretical basis for the clinical application.OBJECTIVE： To investigate the clinical efficacy and safety of the use of high-dose CTX following haploidentical allo-HSCT in SAA children.METHODS： Clinical data from 10 children with SAA undergoing haploidentical allo-HSCT at the Department of Hematology, General Hospital of Beijing Military Area from January 2013 to January 2015 were retrospectively analyzed. Pretreatment was CTX, fludarabine, Busulfex combined with anti-human lymphocyte immune globulin used for 2 consecutive days, and then 3 days after transplantation, CTX（50 mg/kg per day） was used to induce immunogenic tolerance. Combined use of cyclosporin A,methotrexate and tacrolimus functioned as a prophylaxis for graft-versus-host disease. Another 10 SAA children who underwent synchronous HLA-identical sibling HSCT served as controls. Complications and survival in children were statistically analyzed in the two groups.RESULTS AND CONCLUSION： In the treatment group, children were followed up until May 2015, and the median follow-up period was 18.1 months（5-28 months）. Hematopoietic reconstruction was successful in all cases, and there were three cases of graft-versus-host disease, three cases of pulmonary infection and two cases dying of pulmonary infection. In the control group, the median follow-up period was 20.7 months（6-27 months）, and all the children received hematopoietic reconstruction. Additionally, there were two cases of graft-versus-host disease, four cases of pulmonary infection, one case dying of graft-versus-host disease and one case dying of pulmonary infection in the control group. The total survival rate in each group was 80%. In summary, high-dose CTX-induced immunogenic tolerance is
出处
《中国组织工程研究》
CAS
北大核心
2016年第32期4818-4824,共7页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金:DKK-1在间充质干细胞诱导免疫耐受机制中的调控作用(31200686)
北京市首都临床特色课题:诱导耐受新方法造血干细胞移植治疗重型再生障碍性贫血的临床研究~~
