肾移植加造血干细胞移植作为诱导疗法:单中心10年经验

Chineae Journal of Organ Transplantation Pub Date : 2019-05-20 DOI:10.3760/CMA.J.ISSN.0254-1785.2019.05.007

Xuanchuan Wang, Linkun Hu, Zheng Wei, Q. Tang, Bi-Le Chen, Zhaochong Zeng, Yuan Ji, Ming Xu, R. Rong, T. Zhu

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引用次数: 0

摘要

目的探讨肾移植联合造血干细胞移植诱导免疫耐受的疗效，并总结其远期随访结果。方法对2009 - 2018年11例活体亲缘供肾联合造血干细胞移植进行回顾性分析。其中2人HLA匹配，其余人HLA单倍型不匹配。移植前5天用粒细胞集落刺激因子动员供体造血干细胞，术前1天收集供体造血干细胞。移植前接受全淋巴照射3天，移植期间接受抗胸腺细胞球蛋白诱导。分别于术后第2、4、6天输注供体造血干细胞。检测术后调节性T细胞、嵌合、B细胞活化因子及混合淋巴细胞培养等参数，并跟踪长期随访结果。结果免疫耐受诱导受体活化Treg显著升高。1例hla匹配受体嵌合率达到30%-50%，6个月后嵌合率下降。然而，其他接受者并没有实现混合嵌合。受体BAFF在移植后急剧上升。混合淋巴细胞培养提示供体特异性低反应。研究人员对受助人进行了717至3612天的随访。1例患者肾功能丧失，10例患者肾功能稳定。所有受者均无骨髓抑制或移植物抗宿主病。同种异体移植活检证实只有一例轻微急性排斥反应。5例患者降低免疫抑制剂剂量。结论造血干细胞移植诱导肾移植耐受是安全的。嵌合是诱导免疫耐受的必要条件。关键词:活体供体;肾移植;造血干细胞移植;嵌合现象;宽容

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Renal transplantationplus hematopoietic stem cell transplantation as Induction therapy: a single-center 10-year experience

Objective To explore the efficacy of renal transplantation plus hematopoietic stem cell transplantation on inducing immune tolerance and summarize its long-term follow-up outcomes. Methods From 2009 to 2018, a total of 11 cases of living related donor kidney transplantation plus hematopoietic stem cell transplantation were performed. Two of them were HLA-matched and the remainder were mismatched for one HLA haplotype. The donor hematopoietic stem cells were mobilized using granulocyte colony-stimulating factor at 5 days pre-transplantation and collected at 1 day pre-operation. The recipients received total lymphoid irradiation for 3 days pre-transplantation and received anti-thymocyte globulin induction during transplantation. The donor hematopoietic stem cells were infused at 2, 4 and 6 postoperative day. Postoperative regulatory T cells, chimerism, B cell activating factor and mixed lymphocyte culture and other parameters were detected and long-term follow-up outcomes tracked. Results The immune tolerance-inducible recipients had a significant increase in activated Treg. One HLA-matched recipient achieved 30%-50% of chimerism and lost after 6 months. However, other recipients did not achieve mixed chimerism. The BAFF of recipient spiked sharply after transplantation. Mixed lymphocyte culture indicated that a donor-specific low response was induced. The recipients were followed up for 717 to 3612 days. The first recipient lost renal function and another ten recipients had stable renal function. None of the recipients had myelosuppression or graft-versus-host disease. Allograft biopsy confirmed only one case of mild acute rejection. The dose of immunosuppressive agents was lowered in 5 patients. Conclusions Hematopoietic stem cell transplantation for inducing tolerance is safe during renal transplantation. And chimerism is essential for inducing immune tolerance. Key words: Living donor; Kidney transplantation; Hematopoietic stem cell transplantation; Chimerism; Tolerance

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Chineae Journal of Organ Transplantation

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