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自体外周血纯化CD34+干细胞移植治疗系统性红斑狼疮

[Transplantation of purified CD34+ stem cells from autologous peripheral blood for treatment of systemic lupus erythematosus].

作者信息

Zeng Kang, Peng Xue-Biao, Sun Jing, Xu Dan, Meng Fan-Yi

机构信息

Department of Dermatology, First Military Medical University, Guangzhou 510515, China.

出版信息

Di Yi Jun Yi Da Xue Xue Bao. 2002 Nov;22(11):1052.

PMID:12433652
Abstract

We used the transplantation of purified autologous peripheral blood CD34+ stem cells to treat a 16-year-old female patient with systemic lupus erythematosus (SLE), who had received unsuccessful treatment with steroids and immunosuppressants, and has achieved satisfactory therapeutic effect. The diagnosis of SLE was established one year ago, and the patient had SLE Disease Activity Index (SLEDAI) of 21 on admission. After ineffective treatment with dexamethasone and cyclophosphamid (CTX) for 3 months, purified autologous peripheral blood CD34+ stem cell transplantation was adopted. Autologous peripheral hematopoietic stem cells were mobilized by intravenous injection of 2.0 g/d cyclophosphamid (CTX) for 3 d and subcutaneous injection of granulocyte colony-stimulating factor (G-CSF, 300 microgram/d). A CS-3000 plus blood cell separator was used to collect peripheral blood stem cells, and cell count of mononuclear cells and CD34+ stem cells and epitope analysis of T and B lymphocytes were performed by FACscan flow cytometry. After purification with CliniMACS, the number of CD34+ stem cells reached 15.13x106/kg, while that of CD3+ cells were only 1.35x105/kg. Pretreatment of the patient consisted of intravenous injection of (50 mg/kg each day)for 4 consecutive days and antithymocyte globulin (ATG, 2.5 mg/kg each day) for 3 consecutive days with methylprednisolone (MP) at the dose of 1.0 g on the first day and 0.5 g on the following 2 days. The granulocytes were recovered by G-CSF stimulation. The purified CD34+ stem cells (60 ml) were reinfused within 24 h after pretreatment, following which changes in clinical manifestations and immunologic markers were compared with those before the transplantation. Clinical and immunologic remissions were achieved after transplantation, with all the autoantibodies reversed to the negative, suggesting the short-term effectiveness of this therapy. Based on this observation, we conclude that this therapy is possible to effect an eventual cure of SLE in this case, but the long-term effect needs to be further observed in the follow-up study.

摘要

我们采用纯化的自体外周血CD34+干细胞移植治疗一名16岁的系统性红斑狼疮(SLE)女性患者,该患者接受类固醇和免疫抑制剂治疗无效,但取得了满意的治疗效果。SLE诊断于一年前确立,患者入院时SLE疾病活动指数(SLEDAI)为21。在接受地塞米松和环磷酰胺(CTX)治疗3个月无效后,采用纯化的自体外周血CD34+干细胞移植。通过静脉注射2.0g/d环磷酰胺(CTX)3天并皮下注射粒细胞集落刺激因子(G-CSF,300μg/d)动员自体外周造血干细胞。使用CS-3000 plus血细胞分离机采集外周血干细胞,并通过FACscan流式细胞术进行单核细胞和CD34+干细胞计数以及T和B淋巴细胞表位分析。经CliniMACS纯化后,CD34+干细胞数量达到15.13×10⁶/kg,而CD3+细胞数量仅为1.35×10⁵/kg。患者预处理包括连续4天静脉注射甲基强的松龙(MP,50mg/kg/天),并连续3天静脉注射抗胸腺细胞球蛋白(ATG,2.5mg/kg/天),第一天剂量为1.0g,后两天剂量为0.5g。通过G-CSF刺激使粒细胞恢复。纯化的CD34+干细胞(60ml)在预处理后24小时内回输,随后将临床表现和免疫标志物的变化与移植前进行比较。移植后实现了临床和免疫缓解,所有自身抗体均转为阴性,表明该疗法具有短期有效性。基于此观察结果,我们得出结论,该疗法有可能最终治愈该例SLE,但长期效果需要在后续研究中进一步观察。

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