造血干细胞移植治疗X-连锁重症联合免疫缺陷病临床观察

Clincal analysis of 4 children with severe combined immunodeficiency treated by hematopoietic stem cell transplantation

目的:探讨重症联合免疫缺陷(SCID)移植的经验。方法:对我院4例X-连锁SCID患者进行了5次造血干细胞移植(HSCT)。供者采用人类白细胞抗原(HLA)全相合同胞骨髓1例次,母亲半相合CD34+外周造血干细胞2例次,无关脐血2例次。2例次脐血移植者应用了清髓性预处理,并进行移植物抗宿主病(GVHD)预防,其余3例次未进行预处理和GVHD预防。结果:所有患者在活动性感染的基础上接受HSCT。骨髓和外周血移植物平均CD34+细胞为6.45×107/kg,脐血为1.38×106/kg。3例患者移植后2周左右出现Ⅰ～Ⅱ度急性GVHD。最终2例因移植后肺部感染加重死亡,1例因黄疸、肝功能不良放弃治疗,仅1例接受再次脐血移植者经历了首次移植失败、重度肝静脉阻塞病(VOD)、重症肺炎后幸存,该患儿移植后78d自然杀伤(NK)细胞数量接近正常,10个月免疫球蛋白数量恢复正常,13个月T细胞数量接近正常,目前已经随访到移植后15个月。结论:HSCT治疗SCID具有可行性,早期诊断并在严重感染前进行移植是提高移植成功的关键。

Objective To offer the experience of hematopoietic stem cell transplantation （HSCT） for children with severe combined immunodeficiency （SCID）. Methods Five HSCT were performed in 4 X-linked SCID patients including 1 patient received a second HCST because of graft failure in first transplantation. One received human leukocyte antigen （HLA） matched related bone marrow, 2 received haploidentical peripheral hematopoetie stem cell from mother and another 2 received unrelated umbilical cord blood. Myeloablative conditioning and graft versus host disease （GVHD） prophylaxis were given in the two patients receiving unrelated umbilical cord blood transplant. Another 3 HSCT were performed without conditioning and GVHD prophylaxis. Results All patients received HSCT under the status of active infection. The average CD34^＋ cell was 6.45×10^7/kg in patients receiving bone marrow or peripheral hemopoietic stem cell transplantation and 1.38×10^6/kg in patients receiving umbilical cord blood. Three of 4 patients suffered grade Ⅰ-Ⅱ acute GVHD at about 14 d after transplantation. Two patients died of severe pneumonia, 1 patient give up treatment because of jaundice and liver dysfunction. Only 1 patient survived after experiencing primary graft failure, severe hepatic veno-occulsive disease and severe pneumonia with the nature killer cell count recovered to near normal at 78 d, immunoglobulin reached to normal at 10 months and CD3^＋T lymphocyte cell count to near normal at 13 months. Conclusions HSCT is feasible for SCID. Diagnosis at earlier stage and transplant before the occurrence of severe infection is critical for the success in transplantation.