Association of Immunosuppressive Maintenance Regimens With Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients: 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.
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