自体外周血干细胞移植治疗系统性自身免疫病

Treatment of severe systemic autoimmune diseases with autologous peripheral blood stem cell transplantation

目的探讨大剂量化疗并自体外周血干细胞移植治疗重症/难治性系统性自身免疫病的可行性、疗效及安全性。方法对包括系统性红斑狼疮(SLE)、类风湿关节炎(RA)、原发性干燥综合征(pSS)、系统性硬化症(SSc)、混合性结缔组织病(MCTD)在内的21例常规治疗不能缓解病情的重症/难治性系统性自身免疫病患者给予大剂量免疫抑制剂并自体外周血干细胞移植治疗。采用环磷酰胺(CTX)3～4g/m2及粒细胞集落刺激因子(GCSF)行干细胞动员,并行CD34+细胞分选。预处理方案采用环磷酰胺200mg/kg+抗胸腺细胞免疫球蛋白(ATG)90mg/kg或环磷酰胺200mg/kg+全身照射4～6Gy,之后进行分选后的造血干细胞回输。结果21例患者中2例死于移植相关并发症,分别为巨细胞病毒感染和粒细胞缺乏时的严重肺部感染。1例于干细胞动员后等待移植前死于原发病。2例SLE患者分别于移植后26、37个月复发,1例RA患者于移植后15个月复发。其余SLE患者随访超过6个月者,其疾病活动评分(SLEDAI)平均由移植前17分降至移植后2分,尿蛋白由67g降至23g;RA患者的简明疾病活动评分(DAS28)下降;pSS患者的症状改善,唾液流率等客观检查恢复正常。结论对于常规治疗无效的重症、难治性自身免疫病,自体外周血干细胞移植是可供选择的治疗方案,可使病情达到短期和中期缓解。

Objective To investigate the feasibility, efficacy and safety of high dose immunosuppressive therapy(HDIT) and autologous peripheral blood stem cell transplantation(PBSCT) with CD + 34 cell selection in patients with refractory and severe autoimmune diseases.Methods Tweenty one patients with SLE, RA, pSS, SSc or MCTD were enrolled in the study from 1999. Autologous haemopoietic stem cells were mobilized with CTX 3～4 g/m 2 and granulocyte colony stimulating factor (G CSF). CD + 34 cells were selected by CliniMACS. After conditioning with CTX (200 mg/kg) and pig antithymocyte globulin(ATG, 90 mg/kg) or CTX(150 mg/kg) and total body irradiation(TBI, 4～6 Gy), the enriched CD + 34 cells were reinfused. Results All patients completed the mobilization and leukapheresis procedures successfully, and proceeded to receive conditioning and transplantation. Two patients died of complication related to transplantation, one is CMV infection, the other is severe pneumonia during the course of granulocyte deficiency. A MCTD patient completed the stem cell mobilization and died of severe pulmonary hypertension and heart failure before CD + 34 cells reinfusing. Two SLE patients relapsed in 26, 37 months respectively and a RA patient relapsed in 15 months after transplantation. Other patients got improved, with SLE DAI score decreasing from 17 to 4 score and proteinuria decreasing from 6 7 g to 2 3 g in SLE patients; DAS28 score from 7 9 to 2 1 in RA patient; Symptom improved and lab results recovered in SS.Conclusion High dose immunosuppressive therapy followed by autologous peripheral blood stem cell transplantation with CD + 34 cell selection is feasible and relative safe. Patients remain free from disease active and improved continuously. Some patients could relapse after transplantation. Long term effect need to be further observed.