异基因造血干细胞移植治疗重型再生障碍性贫血临床研究

Allogeneic stem cell transplantation for severe aplastic anaemia

目的探讨异基因造血干细胞移植成功治疗重型再生障碍性贫血的疗效与治疗经验。方法对15例重型再生障碍性贫血患者进行同胞间人组织相容性抗原（HLA）不全相合/HLA全相合造血干细胞移植,观察移植疗效及并发症,结合相关文献讨论分析。结果移植后9~24 d（中位时间13.8 d）中性粒细胞大于0.5×109/L;移植后14~26 d（中位时间17.3 d）血小板大于20×109/L。2例于移植后26 d（HLA 3/6相合）和移植后48 d（HLA-A、DR各一个位点不合）发生Ⅱ度急性移植物抗宿主病（GVHD）,予甲强龙治疗后控制;9例发生慢性GVHD,其中局限型6例（1例为HLA全相合,1例为HLA-B一个位点不合,4例HLA 3/6相合）,广泛型3例[其中1例为HLA-DR一个位点不合,1例为4/6相合（HLA-A、B不合）,1例HLA 3/6相合];4例发生肺部感染,3例发生肠道感染,1例巨细胞病毒感染;1例出现肝功能损害,无1例发生肝静脉闭塞病（VOD）;随访3~37个月,14例患者无病生存,1例死于肺部侵袭性真菌感染。结论异基因造血干细胞移植是治疗重型再生障碍性贫血的可靠方法,在充分考虑移植风险和积极准备的基础上可实施HLA不全相合造血干细胞移植。

Objective To explore the feasibility and effect of allogeneic stem cell transplantation for severe aplastic anaemia.Methods Fifteen cases of HLA partially-mismatched or HLA matched allogeneic stem cell transplantation for severe aplastic anaemia was reported.And the treatment experience for this disease was reviewed.Results ＋9～＋24 days（median time ＋13.8 days）after transplantation,all patients had neutrophils count above 0.5×109/L,＋14～＋26 days（median time ＋17.3 days）after transplantation,all patients had platelet count above 20×109/L.Grade II acute GVHD developed in two cases and was finally controlled by Methylprednisolone.Chronic GVHD developed in 9 cases（6 cases of focal type and 3 cases of diffused type）.And infection of lung（4 cases）,infection of intestine（3 cases）occurred and were properly disposed.One case of hepatic damage and one case of CMV infection happened and there was no VOD in all 15 cases.Among 15 patients,3 patients had HLA-matched donors,8 patients had HLA half-matched donors and other patients had HLA mismatched donors.All patients had been followed up for 3 to 37 months and 14 patients survived disease free and only 1 patients died of invasive fungus infection in lung.Conclusion Take into consideration of the risks and with careful preparation,allogeneic stem cell transplantation is a feasible and effective method for severe aplastic anaemia treatment.