单倍体造血干细胞联合脐带间充质干细胞移植对再生障碍性贫血的临床观察及其促进造血机制的初步疗效研究

Clinical Effect of Transplantation of Haploid Hematopoietic Stem Cells Combined with Cord Mesenchymal Stem Cells in Treating Aplastic Anemia

目的探讨单倍体造血干细胞联合脐带间充质干细胞移植治疗再生障碍性贫血的初步疗效。方法选取2012年12月至2014年12月间我院收治的5例再生障碍性贫血患者为研究对象,给予患者单倍体造血干细胞联合脐带间充质干细胞移植治疗。术后观察患者回输的MNC、CD34+细胞数,GVHD发生率,血象恢复时间,SDF-1α、G-CSF、IL-6、GM-CSF、TPO、IL-11、SCF等细胞因子变化情况,以及骨髓有核细胞磷酸化ERK1/2蛋白改善情况,并统计并发症发生情况。结果 5例患者均获得造血重建,移植后血小板恢复时间平均为15 d,血细胞恢复时间平均为10.4 d。3例患者发生Ⅲ度a GVHD,3例患者发生局限性c GVHD,经治疗后均好转,4例患者恢复良好,1例患者术后73 d死于真菌性肺炎。移植后患者血清SDF-1α、G-CSF、IL-6、GM-CSF、TPO以及SCF水平明显改善(P<0.05);治疗后骨髓有核细胞磷酸化ERK1/2蛋白明显高于治疗前(P<0.05);1例患者EB病毒血症,2例出血性膀胱炎,2例真菌性肺炎。结论单倍体造血干细胞联合脐带间充质干细胞移植治疗再生障碍性贫血疗效显著,能够明显改善患者骨髓造血微环境,安全且并发症低,值得进一步开展临床应用研究。

Objective To investigate the clinical effect of transplantation of haploid hematopoietic stem cells combined with cord mesenchymal stem cells in the treatment of aplastic anemia. Methods From December 2012 to December 2014, 5 cases with aplastic anemia were treated with haploid hematopoietic stem cells combined with cord mesenchymal stem cells transplantation. The MNC, CD34＋cells, GVHD incidence, blood recovery time, changes of related growth factors （like SDF-1α, G-CSF, IL-6, GM-CSF, TPO, SCF）, the improvement of bone marrow nucleated cells protein phosphorylation ERK1/2 and complications were all observed. Results Five patients obtained hematopoietic reconstitution with MNC of 11.27 ×108 cells/Kg and CD34＋ of 4.0 ×106 cells/Kg. The average platelet recovery time was 15 days and the average recovery time of blood cells was 10.4 days. aGVHD of stage III was observed in 3 patients, localized cGVHD was observed in 3 patients, and they were all improved after treatment. Four patients recovered well, one patient died of fungal pneumonia 73 days after treatment. After transplantation, serum SDF-1α, G-CSF, IL-6, GM-CSF, TPO and SCF were significantly improved （P〈0.05）, the expression of phosphorylation ERK1/2 protein of bone marrow nucleated cells was significantly increased （ P〈0.05）. Onenbsp;case of EB viremia, two cases of hemorrhagic cystitis and two cases of fungal pneumonia were observed. Conclusion Haploid hematopoietic stem cells combined with cord mesenchymal stem cell transplantation is effective in the treatment of aplastic anemia, it can significantly improve the bone marrow microenvironment of patients with higher safety and lower complication. It is worthy of further clinical application.