Ailawadi Gorav, Smith Philip W, Oka Tomomi, Wang Hongkun, Kozower Benjamin D, Daniel Thomas M, Kron Irving L, Jones David R
Department of Surgery, University of Virginia, Charlottesville, VA 22908-0679, USA.
J Thorac Cardiovasc Surg. 2008 Mar;135(3):594-602. doi: 10.1016/j.jtcvs.2007.10.044. Epub 2008 Jan 18.
Effects of daclizumab and antithymocyte globulin induction on acute rejection, bronchiolitis obliterans syndrome, and survival after lung transplantation are unknown. We hypothesized that daclizumab results in less acute rejection and bronchiolitis obliterans and better survival than antithymocyte globulin.
Consecutive adult lung transplants (n = 163) at the University of Virginia from January 1998 to May 2006 were reviewed. Antithymocyte globulin induction was routinely performed before January 2002 (65 patients), after which all patients received daclizumab (98 patients). Estimates of cumulative event rate of acute rejection, bronchiolitis obliterans, and death were calculated by Kaplan-Meier method and between-group differences compared by log-rank test. Cox proportional hazards models were fitted to assess treatment effects adjusted for covariates.
Groups were similar in demographics and preoperative and intraoperative risk factors. Maintenance immunosuppression changed during the study, and mycophenolate mofetil was more commonly given to patients receiving daclizumab. By Kaplan-Meier method, daclizumab was associated with significantly less acute rejection (P = .002), less bronchiolitis obliterans (P = .02), and improved overall survival (P = .04). Induction agent was highly associated with acute rejection (P = .002), bronchiolitis obliterans (P = .02), and mortality (P = .05); antimetabolite agent was associated only with acute rejection (P = .01). Adjusting for covariates, induction agent remained significantly predictive for acute rejection (P = .02) and bronchiolitis obliterans (P = .05), approaching significance for survival (P = .07).
Lung transplant recipients receiving daclizumab for induction had significantly less acute rejection and bronchiolitis obliterans than those receiving antithymocyte globulin, with possibly improved survival. Improvements in acute rejection may have been confounded by the use of mycophenolate mofetil.
达利珠单抗和抗胸腺细胞球蛋白诱导治疗对肺移植术后急性排斥反应、闭塞性细支气管炎综合征及生存率的影响尚不清楚。我们假设,与抗胸腺细胞球蛋白相比,达利珠单抗可减少急性排斥反应和闭塞性细支气管炎的发生,并提高生存率。
回顾了1998年1月至2006年5月在弗吉尼亚大学进行的连续成人肺移植手术(n = 163例)。2002年1月之前常规采用抗胸腺细胞球蛋白诱导治疗(65例患者),此后所有患者均接受达利珠单抗治疗(98例患者)。采用Kaplan-Meier法计算急性排斥反应、闭塞性细支气管炎和死亡的累积事件发生率,并通过对数秩检验比较组间差异。采用Cox比例风险模型评估调整协变量后的治疗效果。
两组患者在人口统计学特征以及术前和术中危险因素方面相似。在研究期间维持免疫抑制方案有所变化,接受达利珠单抗治疗的患者更常使用霉酚酸酯。采用Kaplan-Meier法分析,达利珠单抗组的急性排斥反应显著减少(P = 0.002),闭塞性细支气管炎较少(P = 0.02),总体生存率提高(P = 0.04)。诱导治疗药物与急性排斥反应(P = 0.002)、闭塞性细支气管炎(P = 0.02)和死亡率(P = 0.05)高度相关;抗代谢药物仅与急性排斥反应相关(P = 0.01)。调整协变量后,诱导治疗药物对急性排斥反应(P = 0.02)和闭塞性细支气管炎(P = 0.05)仍具有显著预测性,对生存率的预测接近显著水平(P = 0.07)。
与接受抗胸腺细胞球蛋白诱导治疗的患者相比,接受达利珠单抗诱导治疗的肺移植受者急性排斥反应和闭塞性细支气管炎明显减少,生存率可能有所提高。急性排斥反应的改善可能因使用霉酚酸酯而受到混淆。