Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study
Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study
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DOI：
10.1016/s0140-6736(00)02627-1
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发表时间：
2000-08-26
期刊：
影响因子：
168.9
通讯作者：
Burt, RK
中科院分区：
文献类型：
--
作者：
Traynor, AE;Schroeder, J;Burt, RK
背景：尽管标准剂量的静脉注射环磷酰胺，系统性红斑狼疮（SLE）患者仍经历持续的多器官功能障碍，这是早期死亡高风险患者的一个亚群。我们研究了免疫抑制和自体造血干细胞输注治疗此类患者的安全性和有效性。方法从1996年开始，我们选择了使用环磷酰胺的持续性SLE患者，患者接受了大剂量免疫抑制和自体造血干细胞（CD34）输注。移植前后外周血淋巴细胞采用流式细胞术、ELISA和t细胞受体谱分型分析。我们每天用2.0 g/m(2)环磷酰胺和10 μ g/kg粒细胞集落刺激因子动员自体造血干细胞，富集cd34阳性选择，免疫抑制后再输注200 mg/kg环磷酰胺、1 g甲基强龙和90 mg/kg马抗胸腺细胞球蛋白。结果9例患者进行了干细胞动员，2例因感染而在移植前被排除。其余7名接受了大剂量化疗和干细胞输注。中性粒细胞绝对计数高于0.5x10(9)/L和非输注血小板计数高于20x10(9)/L的中位时间分别为9天（范围8-11）和11天（10-13），中位随访25个月（12-40），所有患者均无活动性狼疮症状。肾、心、肺和血清学标志物，以及t细胞表型和储备恢复正常，解释患者在移植后仍然没有活动性狼疮，并且持续改善，没有免疫抑制药物或少量残留剂量的强的松，t细胞储备多样性和反应性恢复。缓解的持久性仍有待确定。
Background Patients with systemic lupus erythematosus (SLE) who experience persistent multiorgan dysfunction, despite standard doses of intravenous cyclophosphamide, represent a subset of patients at high risk of early death. We investigated the safety and efficacy of immune suppression and autologous haemopoietic stem-cell infusion to treat such patients.Methods From 1996, we selected patients with persistent SLE despite use of cyclophosphamide, Patients underwent dose-intense immune suppression and autologous haemopoietic stem-cell (CD34) infusion. Peripheral blood lymphocytes were analysed by flow cytometry, ELISA, and T-cell-receptor spectratyping before and after transplantation. We mobilised autologous haemopoietic stem cells with 2.0 g/m(2) cyclophosphamide and 10 mu g/kg granulocyte colony stimulating factor daily, enriched with CD34-positive selection, and reinfused after immunosuppression with 200 mg/kg cyclophosphamide, 1 g methylprednisolone, and 90 mg/kg equine antithymocyte globulin,Results Nine patients underwent stem-cell mobilisation but two were excluded before transplantation because of infection. The remaining seven received high-dose chemotherapy and stem-cell infusion. Median time to an absolute neutrophil count higher than 0.5x10(9)/L and nontransfused platelet count higher than 20x10(9)/L was 9 days (range 8-11) and 11 days (10-13), respectively, At a median follow-up of 25 months (12-40), all patients were free from signs of active lupus. Renal, cardiac, pulmonary, and serological markers, and T-cell phenotype and repertoire had normalised,Interpretation Patients remained free from active lupus and improved continuously after transplantation, with no immunosuppressive medication or small residual doses of prednisone, T-cell repertoire diversity and responsiveness was restored. Durability of remission remains to be established.