POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER IN PRIMARY KIDNEY TRANSPLANT RECIPIENTS WITH EPSTEIN-BARR VIRUS NEGATIVE OR POSITIVE SEROSTATUS

Abstract

P846 Aims: This study was conducted to explore the relationship between Epstein Barr Virus (EBV) serostatus, immunosuppression for induction and discharge maintenance therapies, and other factors on the risk of posttransplant lymphoproliferative disorder (PTLD) development within 400 days after primary deceased or living donor kidney transplants. Methods: The study included over 15,000 primary kidney transplant recipients from the UNOS/OPTN database during 4/1/99-12/31/02, whose pre-transplant EBV serostatus was either positive or negative. Patients were categorized into one of the following induction groups: monoclonal anti-lymphocyte (muromomab-CD3), polyclonal anti-lymphocyte (Anti-thymocyte globulin, thymoglobulin), IL-2 receptor (basiliximab, daclizumab) antibody or no induction. Patients had to be on a discharge maintenance immunosuppression regimen using either cyclosporine (CYA) or tacrolimus (TAC) with azathioprine (AZA) or mycophenolate mofetil (MMF). The analysis also included patient age group, ethnicity (white vs. other), previous malignancy, pre-transplant CMV serostatus, treatment for early acute rejection, and donor type. Multivariate Cox regression models were used to assess the impact of these factors on PTLD by pre-transplant EBV serostatus. Results of the Cox models are presented as relative risk (RR) of PTLD and p-value. Results: The actual incidence of PTLD within 400 days of transplant was 1.05% in EBV seronegative patients and 0.15% in EBV seropositive patients. The table shows the adjusted RR of PTLD for age, CMV serostatus and immunosuppression agents.FigureNote: *MMF effect could not be estimated due to no PTLD events in the AZA group. Conclusions: Younger age was the strongest risk factor for PTLD in EBV negative patients. PTLD in these patients may be related to either transmission of EBV by an EBV positive donor or primary posttransplant EBV infection. In EBV positive patients, CMV seronegativity was strongly associated with an increased risk of PTLD. None of the induction maintenance immunosuppression therapies were associated with a statistically significantly increased risk of PTLD in EBV seronegative patients. In EBV seropositive patients, anti-lymphocyte induction was associated with a marginally increased risk of PTLD. In EBV seronegative patients, TAC was associated with an increased risk of PTLD while MMF was associated with a reduced risk of PTLD. Risk factors for PTLD appeared to differ significantly in EBV seronegative vs. seropositive patients. These data and multiple prior observations confirm the importance of determining pre-transplant EBV serostatus in the donor and recipient.