自体外周血造血干细胞移植治疗重型狼疮性肾炎的临床观察

Autologous hematopoietic stem cell transplantation for severe lupus nephritis

目的：观察自体外周血造血干细胞移植（ASCT）治疗重型狼疮性肾炎（LN）的初步疗效及安全性.方法：选取2011年7月至2014年1月接受ASCT治疗的20例重型LN患者,其中男性8例,女性12例.所有患者符合系统系统性红斑狼疮（SLE）诊断标准,且均经肾活检证实为重型LN,免疫抑制治疗未缓解或反复复发.移植预处理方案为大剂量环磷酰胺（CTX）联合兔抗人胸腺细胞免疫球蛋白（ATG）.分析ASCT治疗LN的疗效、不良反应及复发率情况.疗效分析主要指标为总缓解率,包括完全缓解率和部分缓解率. 结果：患者移植前LN中位病程为45.5月（24.5～71月）,病理分型包括Ⅳ＋Ⅴ型（50％）、Ⅳ型（25％）、Ⅲ＋Ⅴ型（20％）及Ⅲ型（5％）.移植前狼疮活动指数评分平均为14.7±4.28分.所有患者均采集成功,采集的CD34＋细胞数量平均为（7.5±4.12）×106/kg.移植期患者中位粒缺期为7d,粒细胞植入中位时间为8d,血小板植入的中位时间也为8d.移植期间最常见的并发症为发热及胃肠道反应.患者中位随访时间为21月.20例患者中有1例患者移植后3月因重症感染死亡,移植相关死亡率为5％.1例在移植后5月因脓毒症死亡.其余18例患者有14例获得完全缓解,3例部分缓解,1例无反应,总缓解率为85％ （17/20）,其中完全缓解率为70％ （14/20）,肾脏缓解的中位时间为5月.随访期间有2例患者分别在术后15月和27月出现疾病复发.患者3年的总体生存率为90％,复发率为11.1％. 结论：本研究表明ASCT是重型LN的安全有效的治疗手段,临床缓解率高、起效较快且并发症较少.感染仍是导致治疗失败的重要原因,其远期疗效仍需进一步观察.

Objective：To evaluate the efficiency and safety of the treatment of autologous hematopoietic stem cell transplantation （ASCT） for patients with severe lupus nephritis （LN）. Methodology：From Jul 2011 through Jan 2014, a total of twenty patients with severe LN refractory to standard immunosuppressive therapies were enrolled in this study. Peripheral blood stem cells were mobilized with cyclophosphamide （CTX） and granulocyte colony-stimulating factor （G- CSF）, and reinfused after treatment with CTX and antithymocyte globulin. The primary end point was remission rate, and secondary end points included the survival and relapse rate, changes in proteinuria, renal function and serology immunologic test. All the complications were recorded for safety access. Results：They were 8 males and 12 females with a median LN duration of 45.5 months. The IV ＋ V type was the dominant renal pathologic type. The mean SLE Disease Activity Index （SLE-DAI） was 14. 7±4. 28 points. The mean number of CD34＋ cells was （7. 5±4. 12） × 106/kg. All patients had successful engraftment, and the median time of granulocyte and platelet engraftment was both 8 days. The major complications of ASCT were fever and symptom of gastrointestinal tract. Treatment-related mortality was 5% （1/20）. With a mean follow-up of 21 months （range, 6 months to 36 months）, fourteen patients achieved completed remission, 3 partial remission, one had no response; and only one died for sepsis. The median time of renal response was 5 months. The overall 3-year survival was 90%. 2 patients had relapse during the follow- up and the relapse rate was 11.1%. Conclusion：In treatment of severe LN, ASCT could result in amelioration of disease activity, improvement in serologic markers, and stabilization of organ dysfunction.