自体外周血纯化造血干细胞移植治疗系统性红斑狼疮

Autologous peripheral blood stem cell transplantation for the treatment of systemic lupus erythematosus

目的探讨自体外周血纯化造血干细胞移植治疗系统性红斑狼疮(SLE)的疗效和安全性。方法对9例SLE患者进行自体外周血纯化造血干细胞移植。采集的干细胞的计数为(2．37～9．9)×10~8/ kg。预处理方案是环磷酰胺50 mg·kg^(-1)·d^(-1)静脉滴注,连用4 d(造血干细胞回输前2～5d)。抗胸腺球蛋白抗体2．5 mg·kg^(-1)·d^(-1)静脉滴注,连用4 d。同时碱化和水化尿液,保护心、肝和肾功能。从移植后临床表现、SLE相关的免疫学指标的变化,移植后造血重建情况,移植的并发症等方面进行评价。结果9例患者均获得成功植入,外周血白细胞总数＞1．0×10~9/L的时间为移植后7～15 d,血小板＞20×10~9/L时间为移植后0～21d。所有患者均于移植后面部红斑等临床症状完全消失,大部分患者自身抗体转阴。9例患者均出现轻重不一的血清病样反应,1例出现严重的肾衰和心衰,3例有出血性膀胱炎,1例出现心因性精神障碍,1例发生会阴部念珠菌感染。结论随访1年结果表明,自体外周血纯化造血干细胞移植治疗SLE的近期疗效显著,且相对安全。

Objective To explore the efficacy and safety of autologous peripheral blood stem cell transplantation （ APBSCT ） in the treatment of systemic lupus erythematosus. Methods Nine patients with systemic lupus erythematosus were enrolled in this study. Patients were given cyclophosphamide and granulocyte colony-stimulating factor （ G-CSF ） as the mobilization regimen. Urine was alkalinized and hydrolyzed to protect the function of the heart, liver and kidney of the patients. A CS3000 Plus blood cell separator was used to collect peripheral blood stem cells, which were preserved in liquid nitrogen. Two to five days before the administration of the stem cells, the patients were pretreated with intravenous injection of cyclophosphamide （ 50 mg·kg^-1·d^-1 ） for 4 consecutive days and antithymocyte globulin （ ATG, 2.5 mg·kg^-1·d^-1） for 3 consecutive days. Granulocytes were recoverd by G-CSF stimulation. Then, the peripheral blood stem cells were reinfused. Therapeutic effect was evaluated by assessment of alteration of clinical manifestation （ skin erythema ）, levels of proteinuria and antoantibodies, hematopoietic reconstitution and occurrence of transplantation related complications. Results After transplantation, all patients had been successfully engrafted. The time for peripheral leucocyte count to reach 1.0 × 10^9/L was 7 - 15 d; the time for platelets to reach 20 × 10^9/L, was 0 - 21 d. The skin erythema resolved in all patients; proteinuria decreased to normal level and the autoantibodies became negative in most of the patients. Serum sickness-like response occurred in all patients, renal and heart failure in 1 patient, hemorrhagic cystitis in 3 patients, psychiatric disorders in 1 patient, candidal infection in 1 patient. Conclusion One-year foliow up suggests that autologous stem cell transplantation is markedly effective and relatively safe for systemic lupus erythematosus. However, the duration of remission remains to be investigated in a long-term follow up study.