自体外周血造血干细胞移植治疗系统性红斑狼疮的临床观察

Autologous peripheral blood stem cell transplantation for systemic lupus erythematosns

目的探讨自体外周血造血干细胞移植(APBSCT)治疗难治性系统性红斑狼疮(SLE)的临床疗效和安全性。方法10例难治性SLE患者接受APBSCT治疗,应用环磷酰胺(CTX)2～4g/m^2和粒细胞集落刺激因子5～10μg·kg^(-1)·d^(-1)行外周血造血干细胞动员;预处理包括CTX(50 mg·kg^(-1)·d^(-1),-6～-3d)和抗胸腺细胞球蛋白(ATG,15～20 mg·kg^(-1)·d^(-1),-2d、-1d、1d、2 d)。患者输注的CD34^+细胞>2×10~6/kg。评估治疗前后临床表现、SLE疾病活动指数(SLEDAI)和免疫指标的变化。结果APBSCT后10例SLE患者的临床症状缓解,SLEDAI评分降低,均获得造血重建,中性粒细胞>0.5×10~9/L的中位数时间为9.5 d,血小板>20×10~9/L中位数时间是11d;尿蛋白减少或消失,抗核抗体滴度减低或转阴,补体水平升高;移植相关的并发症有:2例败血症,2例巨细胞病毒感染,1例出现肾毒性,3例急性左心衰竭,3例心律失常,无移植相关死亡。结论APBSCT能够改善SLE患者的疾病活动和免疫学指标,是一种有效的治疗难治性SLE的方法,但远期疗效需进一步观察。

Objective To investigate the clinical efficacy and safety of autologous peripheral blood stem cell transplantation （APBSCT） for refractory systemic lupus erythematosus （SLE）. Methods Ten patients with refractory SLE received APBSCT. Peripheral blood stem cells were mobilized by cyclophosphamide （CTX） at 2-4 g/m^2 and granulocyte colony-stimulating factor （G-CSF） at 5-10 μg·kg^-1·d^-1. Pretreatment regimen was consisted of CTX （50 mg·kg^-1·d^-1,-6-3 d）and anti-thymocyte globulin （ATG 15-20 mg·kg^-1·d^-1,-2 d,-1 d,1 d,2 d）. Every patient was infused more than 〉2×10^6/kg CD34^＋ cells. The clinical presentation, SLE disease activity index （SLEDAI） and immunological changes were assessed. Results The clinical manifestations of the 10 patients returned to remission. The SLEDAI score after APBSCT was low. Their hematopoietic reconstitution was successful. The median time for granulocyte count to reach higher than 〉0.5×10^9/L was 9.5 days, and was 11 days for platelet 〉20×10^9/L. The proteinuria decreased or disappeared. The antinuclear antibody decreased or became negative. The level of complement was increased. The following complications were observed： septicemia in 2 patients, cytomegalovirus infection in 2 patients, renal toxicity in 1 patient, acute left heart failure in 3 patients and cardiac arrhythmia in 3 patients. There was no transplantation related mortality. Conclusion APBSCT may improve the disease activity and the immunological markers in SLE. It is a valid therapy for refractory SLE, but the long-term effects need to be observed.