供者干细胞输注治疗接受阿仑单抗的活体亲属肾移植受者的随机试验研究。
A randomized pilot study of donor stem cell infusion in living-related kidney transplant recipients receiving alemtuzumab.
机构信息
1 The Lillian Jean Kaplan Renal Transplant Center of the Division of Transplantation, Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL. 2 Division of Nephrology and Hypertension, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL. 3 Diabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL. 4 Address correspondence to: Dr. Gaetano Ciancio, 1801 NW 9th Avenue, Miami, FL 33136.
出版信息
Transplantation. 2013 Nov 15;96(9):800-6. doi: 10.1097/TP.0b013e3182a0f68c.
BACKGROUND
Transplant tolerance would remove the need for maintenance immunosuppression while improving survival and quality of life.
METHODS
A prospective, randomized pilot study was undertaken to assess the safety and efficacy of donor stem cell infusion (DSCI) in living-related kidney transplant recipients treated with alemtuzumab (C1H) induction and tacrolimus and mycophenolate maintenance with switch to sirolimus and weaning over 2 years.
RESULTS
Four patients received DSCI; five patients were controls. Graft failure occurred in two patients in the DSCI arm. Recurrence of glomerular disease occurred in two DSCI recipients, leading to graft loss in one. Biopsy-proven acute rejection episodes occurred in three patients (two in the DSCI vs. one in the control). One DSCI patient, with recurrence, subsequently developed antibody-mediated rejection leading to graft failure. In the remaining two DSCI patients, weaning was attempted but was not successful. All (4 of 4) DSCI patients had biopsy-proven chronic allograft injury and/or recurrence.
CONCLUSION
DSCI with C1H induction and a steroid-free maintenance regimen in a small group of patients failed to induce tolerance, with suboptimal patient and graft survival. The results do not justify extension of this particular trial and underscore the importance of patient selection, specifically avoidance of patients with glomerulopathies whose recurrence may obscure potential benefit.
背景
移植耐受将消除对维持性免疫抑制的需求，同时提高生存率和生活质量。
方法
进行了一项前瞻性、随机的初步研究，以评估在接受阿仑单抗（C1H）诱导、他克莫司和吗替麦考酚酯维持治疗、随后在 2 年内转换为西罗莫司并逐渐停药的活体亲属肾移植受者中输注供体干细胞（DSCI）的安全性和疗效。
结果
4 例患者接受了 DSCI；5 例患者为对照组。DSCI 组有 2 例患者发生移植物失功。2 例 DSCI 受者发生肾小球疾病复发，导致 1 例移植物失功。3 例患者（DSCI 组 2 例，对照组 1 例）发生经活检证实的急性排斥反应。1 例 DSCI 患者因复发而发生抗体介导的排斥反应，导致移植物失功。在其余 2 例 DSCI 患者中，尝试了逐渐停药，但未成功。所有（4 例中的 4 例）DSCI 患者均经活检证实存在慢性移植物损伤和/或复发。
结论
在一小部分患者中，使用 C1H 诱导和无类固醇维持方案进行 DSCI 未能诱导耐受，患者和移植物的生存率均不理想。这些结果不支持扩展该特定试验，突出了患者选择的重要性，特别是避免复发可能掩盖潜在益处的肾小球疾病患者。
Zotero 插件