Acute rejection, T-cell-depleting antibodies, and cancer after transplantation

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.