异基因造血干细胞移植治疗重型再生障碍性贫血Ⅱ型22例的疗效分析

Outcomes analysis of allogeneic hematopoietic cell transplantation in the treatment of 22 patients with severe aplastic anemia Ⅱ

目的:评估异基因造血干细胞移植(allo-HSCT)治疗重型再生障碍性贫血(SAA)Ⅱ型的疗效和安全性。方法:回顾性分析接受allo-HSCT治疗的22例SAAⅡ患者的临床资料,其中同胞相合供者移植10例,无关供者移植12例;18例行外周血造血干细胞移植,4例行骨髓联合外周血造血干细胞移植。预处理方案为环磷酰胺+抗人胸腺细胞球蛋白±氟达拉滨±白消安±低剂量TBI;采用环孢霉素A或他克莫司、短疗程甲氨蝶呤±霉酚酸酯预防移植物抗宿主病(GVHD)。回输单个核细胞中位数13.55(5.12~25.90)×10~8/kg,CD34^+细胞中位数7.30(2.19~40.32)×10~6/kg。结果:20例(90.91%)患者获得造血重建,可评估患者的中性粒细胞和血小板的中位植入时间分别为12(9~22)d和13(9~28)d。移植后2年急性GVHD、慢性GVHD和移植排斥、移植相关死亡累积发生率分别为40.00%、30.00%、9.09%和22.73%。细菌血流感染率22.73%,肺部侵袭性真菌病发生率40.91%,巨细胞病毒和EBV感染率分别为75.00%和50.00%;心、肝、肾功能不全发生率分别为45.45%、13.64%和36.36%。中位随访23(10~68)个月,17例患者生存,预期2年总生存率77.27%,预期2年无病生存率72.73%。单因素分析结果显示,移植后发生严重(Ⅱ~Ⅳ度)急性GVHD和重要脏器功能不全可显著降低allo-HSCT治疗SAAⅡ的疗效(P=0.018、0.009)。结论:同胞相合供者和无关HLA匹配供者alloHSCT是治疗SAAⅡ的有效手段。

Objective： To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation （allo-HSCT） in severe aplastic anaemia （SAA） Ⅱ patients. Method：The clinical data of 22 SAA Ⅱ patients under-went allo-HSCT were retrospectively analyzed. Ten cases received HLA matched siblings donor （MSD） allo- HSCT,12 cases received unrelated donor （URD） allo-HSCT; 18 patients were subjected to peripheral blood stem cell transplantation （PBSCT）,and 4 patients to mixed transplantation with bone marrow transplantation and PB- SCT. Conditioning regimen was antithymocyte globulin ＋ cyclophosphamide ± fludarabine±busulfan, and/or total body irradiation;GVHD preventing regimen was cyclosporine A/tacrolimus ± methotrexate ± mycopheno-late mofetil. The median reinfusion quantity of mononuclear and CD34＋ cells was 13.55（5.12 to 25.90）×10^8/kg and 7.30（2.19 to 40.32）×10^6/kg, respectively. Result： Hematopoiesis reeonstitution was achieved in 20 recipients （90.91%）. The median time of neutrophils and platelets were 12（9 to 22） d and 13（9 to 28） d in evaluable patients,respectively. The 2-years cumulative incidence of acute GVHD, chronic GVHD, graft rejection and trans-plant-related mortality were 40.00%, 30.00%, 9.09% and 22.73%, respectively. The blood stream infection of bacterial, lung IFD, cytomegalovirus and EB virus were 22.73%, 40.91%, 75.00% and 50.00%, respectively. The cumulative incidence of heart failure,liver and kidney were 45.45%, 13. 64% and 36. 36%, respectively. Median follow-up time was 23（10 to 68） months, 17 patients survived,and estimated OS and EFS for 2 years were 77.27% and 72. 73%,respectively. Univariate analysis showed that severe （Ⅲ to Ⅳ ） aGVHD and important organ dys-function could reduce the efficacy of allo-HSCT for SAA significantly （P= 0. 018,0. 009）. Conclusion： MSD and matched URD allo-HSCT is an effective treatment for SAA Ⅱ patients.