骨髓间充质干细胞移植治疗再生障碍性贫血22例临床观察

 【摘要】　目的　探讨骨髓间充质干细胞（BMSC）移植治疗再生障碍性贫血（AA）患者的疗效和安全性。方法　22例AA患者，中位年龄31岁（12～70岁），包括重型AA 11例，非重型AA 11例；12例曾接受免疫抑制治疗，均无效。从健康供者骨髓中分离培养BMSC，静脉输注给患者，每次输注细胞数为1×106／kg，每周输注1～2次。观察治疗前后患者外周血细胞计数、骨髓细胞学、骨髓活检、外周血CD+3 CD+4、CD+3 CD+8 T淋巴细胞亚群比例及临床症状等，观察治疗相关不良反应。结果　22例患者接受BMSC输注的中位次数为16次（5～83次），中位治疗时间13个月（2～33个月），中位随访23个月（2～34个月）。其中1例患者基本治愈，9例缓解，3例明显进步，3例患者贫血和出血症状好转、输血间隔延长，6例无效；总有效率72.7 %（16／22）。3例曾接受标准方案免疫抑制治疗无效的患者中，2例缓解。14例患者在治疗前外周血CD+4／CD+8细胞比值倒置，治疗后10例恢复正常。所有患者均未出现明显的治疗相关不良反应。结论　BMSC治疗有助于改善AA患者的骨髓造血功能，短期观察未发现不良反应，值得进一步深入及扩大研究。

Clinical observation of bone marrow mesenchymal stem cells transplantation in treatment of 22 patients with aplastic anemia

Objective To explore the efficacy and safety of bone marrow mesenchymal stem cells （BMSC） in treatment of aplastic anemia （AA）. Methods Twenty-two patients with aplastic anemia were enrolled with median age of 31 （12-70） years old, including 11 severe aplastic anemia （SAA）, and 3 of whom were eyclosporine and anti-thymocyte globulin-resistant. BMSC were isolated from bone marrow of healthy donors and cultured. The third to fifth generation cells were administered intravenously in 1×10^6/kg to patients once or twice a week. After infusion, complete blood count, bone marrow aspiration, bone marrow biopsy, flow cytometry analysis of lymphocyte subsets of CD3^＋ CD4^＋ and CD3^＋ CD8^＋ and clinical symptoms were involved in outcome measurement. Results All patients finished 16-time median （5-83 times） infusions of BMSC with 13-month median （2-33 months） treatment course and 23-month median （2-34 months） follow-up. The total response rate was 7：2.7 % （16/22）, including one patient with essential cure, 9 with remission, 3 with remarkably improvement and 3 with transfusion interval extension. Two of three front-line immunosuppressive- resistant SAA patients achieved remission. Ten of 14 patients recovered from inverted ratio of CD4^＋/CD8^＋ cells after BMSC treatment. There were no treatment-related side effects observed in the course of treatment. Conclusion BMSC are effective and safe for the treatment of AA in our preliminary study and they deserve further research with larger-scale and long-term clinical trials.