1 Miami Transplant Institute, Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, and Jackson Memorial Hospital, Miami, FL. 2 Miami Transplant Institute, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, and Jackson Memorial Hospital, Miami, FL. 3 Address correspondence to: Gaetano Ciancio, M.D., Miami Transplant Institute, Jackson Memorial Hospital and The Department of Surgery, University of Miami Miller School of Medicine, P.O. Box 012440 (R-440), Miami, FL 33101.
Transplantation. 2014 Jun 15;97(11):1128-38. doi: 10.1097/01.TP.0000441089.39840.66.
In searching for an optimal induction regimen, we conducted two separate randomized trials of 38 living donor and 90 deceased donor adult, primary kidney transplant recipients comparing antithymocyte globulin (Thymoglobulin) (group A, N=43) versus alemtuzumab (group B, N=43) versus daclizumab (group C, N=42), using exactly the same three treatment arms in each trial.
For the purpose of maximizing statistical power, results from the two randomized trials were combined. Groups A and C received standard maintenance dosing with tacrolimus (TAC), mycophenolate mofetil (MMF), and corticosteroids. Because of intense lymphodepletion expected with alemtuzumab use (and hoped-for achievement of a truer immunoregulatory state), group B received lower TAC and MMF dosing and corticosteroid avoidance. Long-term target TAC trough level and MMF dosing were 5 to 7 ng/mL and 1,000 mg b.i.d. in groups A and C; 4 to 6 ng/mL and 500 mg b.i.d. in group B.
With median follow-up of 95 months, biopsy-proven cute rejection incidence was similar in the three groups (8/43, 14/43, and 12/42, P=0.34), but biopsy-proven chronic allograft injury incidence was significantly higher in group B (19/43) in comparison with groups A (9/43) and C (7/42) combined (P=0.0008). Mean calculated creatinine clearance was significantly lower in group B versus the average of groups A and C means throughout 60 months posttransplant (62.9±4.2 vs. 83.6±6.9 and 79.8±5.9 at 60 months, P=0.01), and death-censored graft failure was significantly higher in group B (13/43) versus groups A (5/43) and C (5/42) combined (P=0.009). Total infection and new-onset diabetes after transplant rates were not significantly different. Ad hoc analysis suggested that the inferior results in group B were specifically a result of reduced dosing and greater withholding of TAC and MMF occurring in that group.
Long-term results clearly indicate inferior clinical outcomes in group B.
在寻找最佳诱导方案的过程中，我们对 38 名活体供体和 90 名已故供体成人原发性肾脏移植受者进行了两项独立的随机试验，比较了抗胸腺细胞球蛋白（Thymoglobulin）（A 组，N=43）、阿仑单抗（B 组，N=43）和达利珠单抗（C 组，N=42），每个试验均采用完全相同的三种治疗方案。
为了最大限度地提高统计学效力，将两项随机试验的结果合并。A 组和 C 组接受标准维持剂量的他克莫司（TAC）、霉酚酸酯（MMF）和皮质类固醇。由于阿仑单抗使用预期会强烈淋巴细胞耗竭（并希望达到更真实的免疫调节状态），B 组接受较低剂量的 TAC 和 MMF 以及避免使用皮质类固醇。A 组和 C 组的长期目标 TAC 谷浓度和 MMF 剂量为 5 至 7ng/ml 和 1000mg bid；B 组的目标为 4 至 6ng/ml 和 500mg bid。
中位随访 95 个月后，三组活检证实的急性排斥发生率相似（A 组 8/43，B 组 14/43，C 组 12/42，P=0.34），但 B 组活检证实的慢性移植物损伤发生率明显高于 A 组（19/43）和 C 组（7/42）（P=0.0008）。与 A 组和 C 组的平均值相比，B 组在移植后 60 个月时的平均肌酐清除率明显较低（62.9±4.2 vs. 83.6±6.9 和 79.8±5.9，P=0.01），B 组的死亡相关移植物失败率也明显高于 A 组（5/43）和 C 组（5/42）（P=0.009）。总感染和移植后新发糖尿病的发生率无显著差异。专题分析表明，B 组的结果较差，特别是由于该组减少了 TAC 和 MMF 的剂量和使用。
长期结果清楚地表明 B 组的临床结果较差。
