McCurry Kenneth R, Iacono Aldo, Zeevi Adrianna, Yousem Samuel, Girnita Alin, Husain Shahid, Zaldonis Diana, Johnson Bruce, Hattler Brack G, Starzl Thomas E
Department of Surgery, The University of Pittsburgh Medical Center, PA 15216, USA.
J Thorac Cardiovasc Surg. 2005 Aug;130(2):528-37. doi: 10.1016/j.jtcvs.2004.09.040.
Acute and chronic rejection remain unresolved problems after lung transplantation, despite heavy multidrug immunosuppression. In turn, the strong immunosuppression has been responsible for mortality and pervasive morbidity. It also has been postulated to interdict potential mechanisms of alloengraftment.
In 48 lung recipients we applied 2 therapeutic principles: (1) recipient pretreatment with antilymphoid antibody preparations (Thymoglobulin [SangStat, Fremont, Calif] or Campath [alemtuzumab; manufactured by ILEX Pharmaceuticals, LP, San Antonio, Tex; distributed by Berlex Laboratories, Richmond, Calif]) and (2) minimal posttransplant immunosuppression with tacrolimus monotherapy or near-monotherapy. Our principal analysis was of the events during the critical first 6 posttransplant months of highest immunologic and infectious disease risk. Results were compared with those of 28 historical lung recipients treated with daclizumab induction and triple immunosuppression (tacrolimus-prednisone-azathioprine).
Recipient pretreatment with both antilymphoid preparations allowed the use of postoperative tacrolimus monotherapy with prevention or control of acute rejection. Freedom from rejection was significantly greater with Campath than with Thymoglobulin (P = .03) or daclizumab (P = .05). After lymphoid depletion with Thymoglobulin or Campath, patient and graft survival at 6 months was 90% or greater. Patient and graft survival after 9 to 24 months is 84.2% in the Thymoglobulin cohort, and after 10 to 12 months, it is 90% in the Campath cohort. There has been a subjective improvement in quality of life relative to our historical experience.
Our results suggest that improvements in lung transplantation can be accomplished by altering the timing, dosage, and approach to immunosuppression in ways that might allow natural mechanisms of alloengraftment and diminish the magnitude of required maintenance immunosuppression.
尽管使用了强效的多种药物免疫抑制疗法，但急性和慢性排斥反应仍是肺移植后尚未解决的问题。反过来，强效免疫抑制导致了死亡率和普遍的发病率。也有人推测它会阻断同种异体移植的潜在机制。
在48例肺移植受者中，我们应用了两种治疗原则：（1）用抗淋巴细胞抗体制剂（胸腺球蛋白[SangStat，弗里蒙特，加利福尼亚州]或Campath[阿仑单抗；由ILEX制药公司，LP，圣安东尼奥，得克萨斯州制造；由Berlex实验室，里士满，加利福尼亚州分销]）对受者进行预处理，以及（2）移植后用他克莫司单一疗法或近乎单一疗法进行最小化免疫抑制。我们的主要分析是针对移植后最初6个月内免疫和感染性疾病风险最高的关键时期的事件。将结果与28例接受达利珠单抗诱导和三联免疫抑制（他克莫司-泼尼松-硫唑嘌呤）治疗的历史肺移植受者的结果进行比较。
用两种抗淋巴细胞制剂对受者进行预处理后，术后可使用他克莫司单一疗法预防或控制急性排斥反应。与胸腺球蛋白（P = 0.03）或达利珠单抗（P = 0.05）相比，使用Campath后无排斥反应的情况明显更好。在用胸腺球蛋白或Campath清除淋巴细胞后，6个月时患者和移植物存活率为90%或更高。胸腺球蛋白组9至24个月后的患者和移植物存活率为84.2%，Campath组10至12个月后的患者和移植物存活率为90%。与我们的历史经验相比，生活质量有了主观改善。
我们的结果表明，通过改变免疫抑制的时机、剂量和方法，有可能实现肺移植的改善，这些改变可能允许同种异体移植的自然机制，并减少所需维持免疫抑制的程度。
