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

摘要

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 × 10 /L and 9-25 days ( median: 13.8 days ) for platelets to reach 20 × 10 /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, Grade Ⅰ ～ 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.%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.