脐带间充质干细胞对人类白细胞抗原不全相合造血干细胞移植治疗重型再生障碍性贫血效果的影响

摘要

目的：探讨不全相合造血干细胞移植联合脐带间充质干细胞(umbilical cord derive mesenchymal Stem cells,UCMSCs)治疗重型再生障碍性贫血(severe aplastic anemia,SAA)的疗效。方法选择我院血液科2007年7月—2013年6月收治的行不全相合造血干细胞移植的 SAA 患者14例,按是否应用 UCMSCs 分为两组,单纯干细胞移植组7例,为亲缘性人类白细胞抗原(HLA)不全相合造血干细胞移植；加 UCMSCS 组 7例,为亲缘性 HLA 不全相合造血干细胞和 UCMSCs 联合移植。观察两组移植后造血重建、慢性移植物抗宿主病(GVHD)及其他移植相关并发症发生情况。结果14例均获供者型造血重建,中性粒细胞中位植活时间、血小板中位植入时间加 UCMSCS 组分别为移植后17(14~21)d、19(18~22)d,单纯干细胞移植组分别为移植后21(19~25)d、21(20~26)d,两组比较差异均有统计学意义(F =10.556,P =0.007；F =6.644,P =0.024)。 aGVHD、cGVHD 发生率加 UCMSCS 组分别为29%、43%,单纯干细胞移植组分别为43%、71%。14例经预处理后均未出现明显肝肾功能损害,仅1例出现肝静脉闭塞症状,经治疗后好转。所有患者中位随访时间14.5(6~74)个月,12例无病生存,单纯干细胞移植组 2例因发生 GVHD,应用免疫抑制剂后引发感染死亡。结论对 SAA 行亲缘性 HLA 不全相合造血干细胞和 UCMSCs 联合移植,可促进造血重建,提高疗效,明显降低 GVHD 发生率及相关病死率。%Objective To investigate the effect of peripheral blood hematopoietic stem cell transplantation ( allo-HSCT)combined with umbilical cord blood mesenchymal stem cell(UCMSC) infusion in treatment of severe aplastic anemia (SAA). Methods 14 patients undergoing haploidentical allo-HSCT in Hematology Department of Bethune International Peace Hospital during July 2007 and June 2013 were divided into two groups according to application of UCMSCs. 7 patients underwent haploidentical allo-HSCT combined MSC infusion. , Other patients underwent haploidentical allo-HSCT only,and hematologic recovery, GVHD related syndrome and complications after the transplantation were observed. Results All the 14 patients achieved hematopoietic reconstitution , the average time of neutrophil and platelet engraftment in the patients undergo-ing haploidentical allo-HSCT combined MSC infusion were 17 (14-21)d and 19 (18-22)d respectively, 21(19-25)d and 21 (20-26)d after haploidentical allo-HSCT. There were significant differences between the two groups ( F = 10. 556, P =0. 007, F = 6. 644, P = 0. 024). The rates of aGVHD and cGVHD were 29% and 43% respectively in the former, 43% and 71% in the latter. 14 pretreated patients did not develop significant liver or kidney damages, hepatic veno-occlusive disease occurred only in one case, which improved after treatment. The median follow-up time was 14. 5 ( 6 to 74 ) months in all the patients. 12 Patients were all alive in disease-free state. 2 patients undergoing haploidentical allo-HSCT developed GVHD and died of sever infection caused by immunosuppressor. Conclusion The haploidentical all-HSCT combined with UCMSCs infu-sion in treatment of SAA can significantly improve the efficacy of treatment and reduce the incidence rate of GVHD and mortal-ity rate.