脐血干细胞移植对儿童重组活化基因突变重症联合免疫缺陷病疗效分析

目的探讨脐血干细胞移植(UCBT)治疗儿童重组活化基因(RAG)突变重症联合免疫缺陷病(SCID)的疗效。方法回顾性分析2015年1月至2019年6月于复旦大学附属儿科医院明确诊断为RAG突变并接受UCBT的8例SCID患儿,其中男6例,女2例。所有患儿均接受白消安(BU)/环磷酰胺(CY)为主的减低毒性预处理方案,采用他克莫司单药预防移植物抗宿主病(GVHD),收集脐血干细胞移植前后的临床及实验室资料,评估患儿治疗效果。不符合正态分布的连续性变量资料用中位数(最小值~最大值)表示,分类资料用例数(相对比)表示。结果8例接受UCBT的RAG突变患儿分析结果显示,脐带血输注中位总有核细胞数为14.73(5.06~27.27)×10^7个/kg,中位CD34+细胞数为4.14(1.75~13.30)×10^5个/kg。8例患儿中7例成功植入,中性粒细胞植入时间25(15~45)d,血小板植入时间34(33~43)d。中位随访时间9.2(0.3~31.3)个月。3例患儿移植早期死亡,5例患儿无病生存并获得免疫重建,脱离静脉丙种球蛋白输注的时间为84(63~100)d。结论UCBT治疗RAG突变所致SCID取得一定疗效。

The outcomes of umbilical cord blood stem cell transplantation for severe combined immunodeficiency disease in children with recombination activating gene mutation

ObjectiveTo investigate the effect of umbilical cord blood stem cell transplantation (UCBT) on children with severe recombination activating genes (RAG) mutation combined with immunodeficiency disease (SCID) . MethodsA retrospective analysis was conducted. Eight children with severe RAG mutation combined with immunodeficiency disease (SCID) , received umbilical cord blood stem cell transplantation (UCBT) at Children's Hospital of Fudan University from January 2015 to June 2019, including 6 males and 2 females. All patients received busulfan (BU) / cyclophosphamide (CY) pre- treatment programs to reduce toxicity, and used tacrolimus monotherapy to prevent graft-versus- host disease (GVHD) . Clinical and laboratory data were collected before and after cord blood stem cell transplantation to evaluate the treatment afterwards. Continuous variable data that do not conform to normal distribution were represented by median (minimum to maximum) and categorical data by case (relative ratio) . ResultsThe results of eight patients who received umbilical cord blood stem cell transplantation (UCBT) showed that the median of total nucleated cells infusion amount was 14.73 (5.06 - 27.27) ×10⁷/ kg and median of CD34⁺ cells amount was 4.14 (1.75 -13.30) ×10⁵/ kg. Of the eight patients, seven were successfully implanted with a median time of neutrophil implantation time 25 (15 - 45) days and a median time of platelet implantation 34 (33 - 43) days. As of the last follow-up, the follow-up time was 9.2 (0.3 - 31.3) months. Three patients died early after transplantation, five survived disease-free and achieved immune reconstitution, the median time to terminate intravenous IV globulin (IVIG) infusion was 84 (63 - 100) days. ConclusionUmbilical cord blood transplantation (UCBT) has achieved certain efficacy in the treatment of severe combined immunodeficiency disease (SCID) caused by RAG gene mutation.