单倍体造血干细胞联合脐带间充质干细胞移植治疗重型再生障碍性贫血-II型的临床观察

Clinical Observation of Haploidentical-Hematopoietic Stem Cell Transplantation Combined with Human Umbilical Cord-derived Mesenchymal Stem Cells for Severe Aplastic Anemia- II

本研究探讨单倍体相合造血干细胞移植联合脐带血间充质干细胞(hUC-MSC)治疗重型再生障碍性贫血-II型(SAA-II)的安全性、有效性及相关并发症的发生情况。对8例重型再生障碍性贫血-II型均进行单倍体造血干细胞移植,移植物选用G-CSF动员的外周血干细胞加骨髓干细胞混合移植方案,并加入脐带间充质干细胞作为第3方细胞;预处理方案采用兔抗人T淋巴细胞球蛋白(ATG)+环磷酰胺(CTX)方案+福达拉滨(Flu)方案,其中2例患者加用马法兰(Bu);移植物抗宿主病(graft-versus-host disease,GVHD)的预防方案采用环孢菌素A+ATG+霉酚酸酯(MMF)+短程甲氨喋呤(MTX)+CD25单克隆抗体。结果表明,8例患者全部获得造血重建,血象好转:中性粒细胞>0.5×109/L平均时间11.9 d;血小板>20×109/L平均时间14.6 d。I-II度急性移植物抗宿主病(aGVHD)发生率25%,Ⅲ-Ⅳ度aGVHD发生率12.5%,移植相关死亡率为25%。结论:联合脐带MSC的单倍体异基因造血干细胞移植治疗SAA-II安全可行,疗效显著,临床可以对其进一步尝试。

This study was purposed to investigate the efficacy and safety of haploidentical hematopoietic stem cells （allo-HSCT） transplantation combined with human umbilical cord-derived mesenchymal stem cell infusion （hUC-MSC） for severe aplastic anemia-Ⅱ（SAA-Ⅱ）. Eight SAA-Ⅱ patients received haploidentical allo-HSCT, the G-CSF mobilized peripheral hematopoietic stem cells and bone marrow haploidentical hematopoietic stem cells were selected as graft, the human umbilical cord-derived mesenchymal stem cells （hUC-MSC） were infused as the third party. Conditioning regimen consisted of rabbit anti-thymiclymphocytes protein （ ATG）, cyclophosphamide （CTX） and fludarabine （Flu）. For two patients out of 8 SAA-Ⅱ patients the conditioning regimen was combined with busulfan（BU）. The graft versus host disease（GVHD） was prevented with CSA, MTX, ATG, CD25 and mycophenolate mofetial. The results showed that the average number of nucleated cells were 9.13 x 10^8/kg, and number of CD34 ＋ cells were 3.76 x 10^9/kg. All the 8 SAA-Ⅱ patients achieved hematopoietic reconstitution. The average time of neutrophils count 〉 0.5 x 10^9/L was 11.9 days, and average time of Pit level 〉 20 x 10^9/L was 14. 6 days. The incidence of acute GVHD of Ⅰ-Ⅱ grade was 25%, and that of Ⅲ-Ⅳ grade was 12. 5%, the transplantation-related mortality was 25%. It is concluded that haploidentical allo-HSCT combined with umbilical cord MSC infusion is an effective approach to cure SAA.