异基因造血干细胞移植治疗重型再生障碍性贫血的疗效研究

Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Treatment of Severe Aplastic Anemia

目的探讨异基因造血干细胞移植(allo-HSCT)治疗重型再生障碍性贫血(SAA)的疗效。方法 8例SAA患者接受allo-HSCT,其中1例接受亲缘白细胞抗原(HLA)全相合allo-HSCT,4例接受单倍体相合allo-HSCT,3例接受非血缘全相合allo-HSCT。预处理方案:非亲缘及亲缘全相合移植采用氟达拉滨(FLU)+环磷酰胺(CTX)+抗人T淋巴细胞球蛋白(ATG);单倍体相合移植采用FLU+CTX+马利兰(BU)+ATG/抗胸腺细胞球蛋白。移植物抗宿主病(GVHD)预防:亲缘全相合移植采用联合免疫抑制剂的方法预防,环孢素A(CSA)+短程氨甲蝶呤(MTX),单倍体相合及非亲缘全相合除以上药物外,加用CD25单克隆抗体和霉酚酸酯(MMF)。结果患者全部获得造血重建,中性粒细胞≥0.5×109/L的时间为10～17 d,中位时间为12.5 d;血小板≥20×109/L的时间为9～25 d,中位时间为13.8 d,植入证据检测证明为完全供者造血。5例合并巨细胞病毒(CMV)血症,3例合并出血性膀胱炎,2例发生急性和慢性Ⅰ～Ⅲ度GVHD,1例合并中枢神经系统感染及纯红再障。8例全部存活,存活时间为9～38个月,中位存活时间为20个月。结论亲缘、非亲缘全相合及单倍型相合的allo-HSCT均是治愈SAA的有效方法,可为患者提供长期生存的机会。

Objective To explore the effectiveness of Allogeneic hematopoietic stem cell transplantation（allo-HSCT） in treating severe aplastic anemia（SAA）.Methods Among the 8 patients,1 patient received allogeneic peripheral stem cell transplantation from an HLA matched sibling,4 patients received allogeneic bone marrow and peripheral stem cell transplantation from haploidentical donors（parents）,3 patients received unrelated allogeneic peripheral stem cell transplantation.Conditioning regimens included：fludarabine,Cyeclophosphamide,anti-themocyte globulin（for unrelated and HLA matched sibling donors）;fludarabine,Cyeclophosphamide,busulphan and anti-lymphocyte globulin（ALG）/anti-themocyte globulin（ATG）（for haploidentical donors）.For prevention of graft versus host disease（GVHD） the patient with HLA matched sibling donor was administered with a combination of immunosuppressive drugs including CSA,short-course MTX while for the patients with haploidentical or unrelated donors,MMF,anti-CD25 monoclonal antibody and ATG were.also employed.Results All the 8 patients achieved hematopoietic reconstitution after transplantation.It took 10～17 days（：median：12.5 days） for the level of neutrophils to reach 0.5×109/L and 9-25 days（median：13.8 days） for platelets to reach 20×109/L.All the 8 patients became donor chimerism.As for the complications,CMV-related sepsis was found in 5 cases,hemorrhagic cystitis in 3 cases,GradeⅠ～Ⅲ graf-versus-host disease（GVHD） and chronic local GVHD in 2 patients,and central nervous system infection accompanied with pure red aplastic anemia in 1 case.All the patients survived during the follow-up（range：9～38 months;median：20 months）.Conclusion Allo-HSCT is an effective approach for treating patients with SAA.It may be helpful to prolong the survivals of these patients.