肾移植中rATg/达利珠单抗与rATg/阿仑单抗作为双重诱导疗法的随机试验:8年随访结果

Randomized trial of rATg/Daclizumab vs. rATg/Alemtuzumab as dual induction therapy in renal transplantation: Results at 8years of follow-up.

作者信息

Ciancio Gaetano, Gaynor Jeffrey J, Guerra Giselle, Sageshima Junichiro, Roth David, Chen Linda, Kupin Warren, Mattiazzi Adela, Tueros Lissett, Flores Sandra, Hanson Lois, Ruiz Phillip, Vianna Rodrigo, Burke George W

机构信息

The Lillian Jean Kaplan Renal Transplant Center and the Miami Transplant Institute, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.

Division of Nephrology of the Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.

出版信息

Transpl Immunol. 2017 Feb;40:42-50. doi: 10.1016/j.trim.2016.11.004. Epub 2016 Nov 22.

Abstract

Our goal in using dual induction therapy is to bring the kidney transplant recipient closer (through more effectively timed lymphodepletion) to an optimally immunosuppressed state. Here, we report long-term results of a prospective randomized trial comparing (Group I,N=100) rATG/Dac (3 rATG, 2 Dac doses) vs. (Group II,N=100) rATG/Alemtuzumab(C1H) (1 dose each), using reduced tacrolimus dosing, EC-MPS, and early corticosteroid withdrawal. Lower EC-MPS dosing was targeted in Group II to avoid severe leukopenia. Median follow-up was 96mo post-transplant. There were no differences in 1st BPAR (including borderline) rates: 10/100 vs. 9/100 in Groups I and II during the first 12mo(P=0.54), and 20/100 vs. 20/100 throughout the study(P=0.90). Equally favorable renal function was maintained in both treatment arms(N.S.). While not significant, more patients in Group II experienced graft loss, 25/100 vs. 18/100 in Group I(P=0.23). Actuarial patient/graft survival at 96mo was 92%/83% vs. 85%/73% in Groups I and II(N.S.). DWFG-due-to-infection(N.S.), EC-MPS withholding-due-to-leukopenia during the first 2mo(P=0.03), and incidence of viral infections(P=0.09) were higher in Group II, whereas EC-MPS withholding-due-to-GI symptoms was higher in Group I(P=0.009). No other adverse event differences were observed. While long-term anti-rejection and renal function efficacy were demonstrated in both treatment arms, slight over-immunosuppression of Group II patients occurred.

摘要

我们使用双重诱导疗法的目标是(通过更有效的适时淋巴细胞清除)使肾移植受者更接近最佳免疫抑制状态。在此,我们报告一项前瞻性随机试验的长期结果,该试验比较了(第一组,N = 100)兔抗人胸腺细胞球蛋白/达珂(3剂兔抗人胸腺细胞球蛋白,2剂达珂)与(第二组,N = 100)兔抗人胸腺细胞球蛋白/阿仑单抗(C1H)(各1剂),采用降低剂量的他克莫司、依维莫司和早期停用皮质类固醇。第二组的依维莫司剂量较低,以避免严重白细胞减少。移植后中位随访时间为96个月。首次活检证实的急性排斥反应(包括临界性排斥反应)发生率无差异:第一组和第二组在最初12个月时分别为10/100和9/100(P = 0.54),在整个研究期间分别为20/100和20/100(P = 0.90)。两个治疗组的肾功能均保持同样良好(无显著差异)。虽然差异不显著,但第二组有更多患者出现移植物丢失,第一组和第二组分别为18/100和25/100(P = 0.23)。96个月时患者/移植物的实际生存率在第一组和第二组分别为92%/83%和85%/73%(无显著差异)。第二组因感染导致的移植物失功(无显著差异)、前2个月因白细胞减少而停用依维莫司的情况(P = 0.03)以及病毒感染发生率(P = 0.09)较高,而第一组因胃肠道症状而停用依维莫司的情况较高(P = 0.009)。未观察到其他不良事件差异。虽然两个治疗组均显示出长期抗排斥和肾功能疗效,但第二组患者出现了轻微的免疫抑制过度现象。

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