1 Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia. 2 Sydney School of Public Health, University of Sydney, New South Wales, Australia. 3 Centre for Transplant and Renal Research, Westmead Hospital, New South Wales, Australia. 4 Department of Medicine, Queen Mary Hospital, Hong Kong. 5 Centre for Kidney Research, The Children's Hospital at Westmead, New South Wales, Australia. 6 Address correspondence to: Wai H. Lim, MBBS, PhD, FRACP, Department of Renal Medicine, Sir Charles Gairdner Hospital, Hospital Avenue, Perth, Australia 6009.
Transplantation. 2014 Apr 27;97(8):817-25. doi: 10.1097/01.TP.0000442773.38510.32.
Systemic inflammatory response has been shown to play a vital role in carcinogenesis and tumor progression. Acute rejection is a systemic inflammatory state and may share a common casual pathway for cancer development after transplantation. The increased burden of immunosuppression used in the treatment of acute rejection, particularly the use of T-cell-depleting antibody may further heighten the risk of cancer development. We aimed to determine the association between acute rejection, T-cell-depleting antibody use and cancer risk after kidney transplantation.
Using the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), we assessed the risk of incident cancer among those who had experienced rejection stratified by the use of T-cell-depleting antibody using adjusted Cox proportional hazard and competing risk models.
A total of 7153 kidney transplant recipients between 1997 and 2009 were included. A total of 467 (6.5%) recipients developed cancers. Recipients who experienced acute rejection and treated with T-cell-depleting antibody were at a 1.4-fold increased risk of cancer (adjusted hazard ratio [HR] 1.42, 95% CI 1.02-1.99, P=0.039) compared with those who did not experience acute rejection. There was an excess risk of genitourinary tract cancers among recipients who had experienced rejection requiring T-cell-depleting antibody compared with recipients who did not experience acute rejection (HR 2.20, 95% CI 1.33-3.66, P=0.007).
Acute rejection requiring T-cell-depleting antibody is a significant risk factor for cancer development in kidney transplant recipients independent of competing events such as age and cardiovascular deaths.
全身性炎症反应已被证明在致癌和肿瘤进展中起着至关重要的作用。急性排斥反应是一种全身性炎症状态，可能与移植后癌症发展存在共同的潜在途径。在治疗急性排斥反应中增加免疫抑制的负担，特别是使用 T 细胞耗竭抗体，可能会进一步增加癌症发展的风险。我们旨在确定急性排斥反应、T 细胞耗竭抗体的使用与肾移植后癌症风险之间的关系。
利用澳大利亚和新西兰透析和移植登记处（ANZDATA），我们使用调整后的 Cox 比例风险和竞争风险模型，评估了在经历排斥反应的患者中，根据 T 细胞耗竭抗体的使用情况，癌症发病风险。
1997 年至 2009 年间，共有 7153 例肾移植受者纳入研究。共有 467 例（6.5%）受者发生癌症。与未经历急性排斥反应的受者相比，经历急性排斥反应并接受 T 细胞耗竭抗体治疗的受者发生癌症的风险增加 1.4 倍（调整后的危险比 [HR] 1.42，95%CI 1.02-1.99，P=0.039）。与未经历急性排斥反应的受者相比，经历需要 T 细胞耗竭抗体的急性排斥反应的受者发生泌尿生殖系统癌症的风险过高（HR 2.20，95%CI 1.33-3.66，P=0.007）。
需要 T 细胞耗竭抗体的急性排斥反应是肾移植受者癌症发展的一个重要危险因素，独立于年龄和心血管死亡等竞争事件。
