title: Association of immunosuppressive maintenance regimens with posttransplant lymphoproliferative disorder in kidney transplant recipients.
abstract: BACKGROUND
  The association of immunosuppressive regimens (ISRs) with posttransplant lymphoproliferative disorder (PTLD) may be related with the Epstein-Barr virus (EBV) recipient serostatus.
  
  
  METHODS
  We selected primary kidney transplant recipients from Organ Procurement Transplant Network/United Network for Organ Sharing database (2000-2009) who were discharged with a functioning graft and were receiving an ISR including an antiproliferative drug and a calcineurin inhibitor as follows: mycophenolate mofetil (MMF)/mycophenolate sodium+tacrolimus (TAC), MMF+cyclosporine A (CsA); mammalian target of rapamycin inhibitor (mTORi)+TAC; and mTORi+CsA. Adjusted risks of PTLD, rejection, death, and graft failure were examined in all recipients and compared between EBV+ and EBV- recipients.
  
  
  RESULTS
  Of 114,025 recipients, 754 developed PTLD (5-year incidence of 0.84%). Adjusted hazard ratio for PTLD was 4.39 (95% CI: 3.60-5.37) for EBV- versus EBV+ recipients; and 1.40 (95% CI: 1.03-1.90) for mTORi+TAC, 0.80 (95% CI: 0.65-0.99) for MMF+CsA, and 0.90 (95% CI: 0.57-1.42) for mTORi+CsA, versus MMF+TAC users. In EBV- recipients, hazard ratio for PTLD was 1.98 (95% CI: 1.28-3.07) for mTORi+TAC, 0.45 (95% CI: 0.28-0.72) for MMF+CsA, and 0.84 (95% CI: 0.39-1.80) for mTORi+CsA users versus MMF+TAC. No difference was seen in EBV+ recipient groups. Rejection rates were higher among MMF+CsA recipients in both EBV groups. Death and graft failure risk were increased in all EBV+ISR groups, while in EBV- these risks were only increased in mTORi+TAC group versus MMF+TAC.
  
  
  CONCLUSIONS
  In EBV- recipients, immunosuppression with mTORi+TAC was associated with increased risk of PTLD, death, and graft failure, while MMF+CsA use was associated with a trend to increased risk of rejection, lower PTLD risk, and similar risk for graft failure when compared with MMF+TAC.
authors: Mendez National Institute of Transplantation, Los Angeles, CA, USA. sampaioms@hotmail.com
authors: Marcelo Santos
authors: MS
authors: Sampaio
authors: Yong W
authors: YW
authors: Cho
authors: Tariq
authors: T
authors: Shah
authors: Suphamai
authors: S
authors: Bunnapradist
authors: Ian V
authors: IV
authors: Hutchinson
mesh_terms: D000293:Adolescent; D000328:Adult; D015897:Comorbidity; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology*; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D004854:Herpesvirus 4, Human; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000276:immunology*; D008137:Longitudinal Studies; D008232:Lymphoproliferative Disorders / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D014180:Transplantation; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D058570:TOR Serine-Threonine Kinases; D009173:Mycophenolic Acid; D016559:Tacrolimus