title: Acute rejection, T-cell-depleting antibodies, and cancer after transplantation.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Wai H
authors: WH
authors: Lim
authors: Robin M
authors: RM
authors: Turner
authors: Jeremy R
authors: JR
authors: Chapman
authors: Maggie K M
authors: MK
authors: Ma
authors: Angela C
authors: AC
authors: Webster
authors: Jonathan C
authors: JC
authors: Craig
authors: Germaine
authors: G
authors: Wong
mesh_terms: D000208:Acute Disease; D000328:Adult; D001315:Australia / Q000453:epidemiology; D001323:Autoantibodies / Q000009:adverse effects* / Q000276:immunology; D001943:Breast Neoplasms / Q000453:epidemiology / Q000276:immunology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000453:epidemiology / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000276:immunology; D008875:Middle Aged; D009520:New Zealand / Q000453:epidemiology; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000276:immunology; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*; D014565:Urogenital Neoplasms / Q000453:epidemiology / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007166:Immunosuppressive Agents