title: Combined introduction of anti-IL2 receptor antibodies, mycophenolic acid and tacrolimus: effect on malignancies after renal transplantation in a single-centre retrospective cohort study.
abstract: BACKGROUND
  Several studies suggest that the introduction of tacrolimus (TRL), mycophenolic acid (MPA) and interleukin 2 receptor antibodies (IL2Ra) as single drugs more than a decade ago has not increased the risk of malignancy after renal transplantation. However, only limited data are available on their carcinogenic effects when used in combination as a potent immunosuppressive regimen.
  
  
  METHODS
  A retrospective single-centre cohort study on 929 adult renal transplant recipients. Investigation of the effect of two consecutive immunosuppressive regimens [1993-98, N = 405, anti-lymphocyte antibodies, cyclosporine and azathioprine (AZA); 1999-2007, N = 524, predominantly IL2Ra, TRL and MPA] on the incidence rate of skin cancer, solid tumours and post-transplant lymphoproliferative disease (PTLD).
  
  
  RESULTS
  In total, 365 malignancies developed among 113 patients. As compared to the previous cyclosporine and AZA-based immunosuppression, the introduction of the new immunosuppressive regimen did not increase the incidence rate of skin cancer [rate ratio 0.84; 95% confidence interval (CI) 0.48-1.46], solid tumours (0.89; 95% CI 0.46-1.67) and PTLD (0.82; 95% CI 0.28-2.21). Patients treated with the more recent regimens less frequently developed multiple skin cancers and invasive squamous cell cancer. Skin cancer after transplantation was strongly associated with the development of solid tumours (odds ratio 5.2; P < 0.0001). The introduction of the new immunosuppressive drugs reduced the incidence of first year acute rejection from 34.8 to 13.2% (P < 0.0001).
  
  
  CONCLUSIONS
  Although significantly more efficient in the prevention of acute rejection, the introduction of TRL, MPA and IL2Ra-based immunosuppression after kidney transplantation was not associated with an increased incidence of skin cancer, solid tumours or PTLD.
authors: Renal Transplantation Clinic, Department of Nephrology, ULB Hopital Erasme, Brussels, Belgium.
authors: Philippe
authors: P
authors: Braconnier
authors: Véronique
authors: V
authors: Del Marmol
authors: Nilufer
authors: N
authors: Broeders
authors: Mireille
authors: M
authors: Kianda
authors: Annick
authors: A
authors: Massart
authors: Anne
authors: A
authors: Lemy
authors: Lidia
authors: L
authors: Ghisdal
authors: Alain
authors: A
authors: Le Moine
authors: Philippe
authors: P
authors: Madhoun
authors: Judith
authors: J
authors: Racapé
authors: Daniel
authors: D
authors: Abramowicz
authors: Karl Martin
authors: KM
authors: Wissing
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D000888:Antibodies, Anti-Idiotypic / Q000009:adverse effects*; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000628:therapy; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects*; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality*; D011379:Prognosis; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D012189:Retrospective Studies; D015996:Survival Rate; D016559:Tacrolimus / Q000009:adverse effects*
chemical_list: D000903:Antibiotics, Antineoplastic; D000888:Antibodies, Anti-Idiotypic; D004338:Drug Combinations; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D009173:Mycophenolic Acid; D016559:Tacrolimus