异基因造血干细胞移植治疗重型再生障碍性贫血

摘要

背景：近年来随着造血干细胞移植技术的提高和免疫抑制剂的使用，重型再生障碍性贫血的治疗效果有了明显改善，尤其是亲缘间HLA配型全相合异基因造血干细胞移植，取得了较高的治愈率。目的：观察异基因造血干细胞移植治疗重型再生障碍性贫血的疗效。方法：自2009至2011年采用异基因造血干细胞移植治疗重型再生障碍性贫血患者20例，HLA配型全相合12例，不全相合8例。移植预处理采用氟达拉滨+兔抗人胸腺细胞免疫球蛋白+环磷酰胺。除1例为非血缘外周血干细胞移植外，其他患者干细胞来源为动员后的骨髓和外周血干细胞联合移植。HLA全相合移植物抗宿主病预防采用环孢素联合短程甲氨蝶呤，不全相合患者采用环孢素、短程甲氨蝶呤联合吗替麦考酚酸酯。结果与结论：移植后中性粒细胞恢复>0.5×109 L-1平均为12.5 d，血小板恢复>20×109 L-1平均为+18 d。20例患者随访24-60个月，总生存率75%(15例)，治愈率70%(14例)，死亡5例；12例全相合患者中83%治愈(10例)，8例不全相合患者治疗有效率62%(5例)，治愈率50%(4例)。20例患者中发生急性及慢性移植物抗宿主病5例，治疗中并发败血症4例，侵袭性真菌感染3例。结果可见异基因干细胞移植是治疗重型再生障碍性贫血的有效方法之一，尤以HLA全相合效果良好，移植后恢复快，移植物抗宿主病发生率低。%BACKGROUND:In recent years, with the development of hematopoietic stem cel transplantation technique and the use of immunosuppressants, the therapeutic effects on severe aplastic anemia have been improved significantly. Especialy relative HLA-identical matching alogeneic hematopoietic stem cel transplantation has achieved a high cure rate. OBJECTIVE:To explore the feasibility of alogeneic hematopoietic stem cel transplantation for the treatment of severe aplastic anemia. METHODS: From 2009 to 2011, 20 patients with severe aplastic anemia received fludarabine, cyclophosphamide and antithymocyte globilin as preconditioning before alogeneic hematopoietic stem cel transplantation from 12 matched and 8 mismatched donors. Except one case undergoing unrelated peripheral blood stem cel transplantation, grafts were from mobilized peripheral blood and bone marrow in al cases. Graft versus host disease prophylaxis consisted of cyclosporine-A and short-course methotrexate in the HLA-identical patients as wel as cyclosporine, methotrexate, and short-course mycophenolate mofetil in HLA-mismatched patients. RESULTS AND CONCLUSION:After transplantation, the time to recover the neutrophil count above > 0.5×109/L was median 12.5 days, and the time to recover the platelet count above > 20×109/L was median 18 days. Twenty patients were folowed up for 24-60 months. The overal survival rate was 75% (n=15), the event-free survival rate was 70% (n=14). Five cases died. The event-free survival rate were 83% (10/12 patients) for HLA-identical patients and 50% (4/8 patients) for HLA-mismatched patients. Acute and chronic graft versus host disease was found in 5 of 20 patients, severe bacterial infection in 4 of 20 patients and fungal infections in 3 of 20 patients. n Alogeneic stem cel transplantation is effective in the treatment of severe aplastic anemia, especialy for HLA-identical patients.