小剂量骨髓联合外周血造血干细胞移植治疗重型再生障碍性贫血18例临床研究

Allogeneic hematopoietic stem cell transplantation with low-dose bone marrow and PBSCs in 18 patients with severe aplastic anemia

目的:探讨小剂量骨髓联合外周血造血干细胞(PBSC)移植治疗重型再生障碍性贫血(SAA)的疗效及安全性。方法:纳入以小剂量骨髓(中位体积200 mL)联合PBSC移植治疗的18例SAA患者的临床资料,回顾分析其造血重建情况、移植物抗宿主病(GVHD)发生率、感染发生率及生存率等指标。结果:18例患者的中位年龄27(13~52)岁,男11例,女7例;SAA-Ⅰ型15例,SAA-Ⅱ型3例;单倍体相合供者15例,同胞全相合供者3例;预处理:氟达拉滨+环磷酰胺+抗人胸腺球蛋白方案2例,氟达拉滨+环磷酰胺+移植后环磷酰胺方案8例,氟达拉滨+环磷酰胺+抗人胸腺球蛋白+移植后环磷酰胺方案8例;采用环孢素或他克莫司+短疗程甲氨蝶呤联合吗替麦考酚酯预防GVHD。所有患者均获得造血重建,仅1例患者出现继发性移植物功能不良;10例(55.6%)出现总计19例次移植后感染,其中10例次为巨细胞病毒(CMV)或EB病毒(EBV)血症,6例次细菌感染;急性GVHD发生率为16.7%,其中Ⅰ度1例,Ⅱ度2例;慢性GVHD发生率为16.7%,均为轻度;中位随访26(2~64)个月,移植后2年总生存率为72.2%(95%CI:51.4~93.0)。5例患者死亡,4例死于肺部感染,1例死于颅内感染。结论:采用小剂量骨髓联合PBSC是SAA患者进行造血干细胞移植的有效且可行的移植物选择策略。

Objective:We analyzed the outcome of patients with severe aplastic anemia(SAA)undergoing allogeneic hematopoietic stem cell transplantation who received both low-dose bone marrow and peripheral blood stem cells(PBSC),and assessed the efficacy and safety of this stem cell source.Methods:In this retrospective cohort study,we included patients with newly diagnosed SAA who received hematopoietic stem cell transplantation with low-dose bone marrow(median 200 mL,range 80-280 mL)and PBSC.The analysis focused on their hematopoietic reconstruction,incidence of graft-versus-host disease(GVHD),occurrence of infections,overall survival rate,and other relevant indicators.Results:The median age of the 18 patients was 27 years(range,13-52).There were 11 males and 11 females.There were 15 cases of severe aplastic anemia type I(SAA-I)and 3 cases of typeⅡ(SAA-Ⅱ).There were 15 cases of haploidentical donors and 3 cases of matched sibling donors.The conditioning regimen consisted of the following:Fludarabine/cyclophosphamide/anti thymocyte globulin regimen(n=2),Fludarabine/cyclophosphamide and post-transplant cyclophosphamide regimen(n=8),Fludarabine/cyclophosphamide/anti thymocyte globulin and post-transplant cyclophosphamide regimen(n=8).Cyclosporine or tacrolimus in combination with methotrexate and mycophenolate mofetil was used to GVHD prophylaxis.All patients achieved durable engraftment,but one patient experienced secondary poor graft function.A total of 10(55.6%)individual patients experienced infections after transplant.Of a total of 19 documented infection events,10 were attributed to CMV or EBV reactivation,and 6 to bacterial infections.The incidence of acute GVHD was 16.7%,including one case of grade I and two cases of grade II,and that of mild chronic GVHD was 16.7%.The two-year overall survival rate was 72.2%(95%CI:51.4-93.0).The mortality of 5 patients was attributed to infectious complications,including 4 cases of pulmonary infections and one case of intracranial infection.Conclusion:The combination of low-dose bone marrow and peripheral blood appears to be a potentially effective and feasible graft source for hematopoietic stem cell transplantation in SAA patients.