Increased Incidence of Post-Transplant Lymphoproliferative Disorder Associated with Mycophenolate Mofetil in Kidney Transplant Recipients

Abstract

846 A three-fold increase in the incidence of post-transplant lymphoproliferative disorder (PTLD) since December 30, 1996 was noted in patients receiving kidney transplants alone. Seven of 8 recently diagnosed patients were seropositive for EBV infection prior to transplantation, and all had received either intravenous or oral ganciclovir prophylaxis. We therefore determined whether the use of specific immunosuppressive agents might be associated with the development of PTLD in this patient group. Seven hundred and two kidney transplants alone (living-related, living-unrelated and cadaveric) were performed at our institution between April 1991 and July 1998. Nine cases of PTLD were diagnosed in the recipients of these transplants; 8 of these occurred after December 30, 1996 in patients transplanted after July 1, 1994. All cases were confirmed by biopsy or necropsy of lymph nodes or other involved organs. The average time to diagnosis was 38.9 ± 10.3 weeks post-transplant. Seven of the 9 cases were classified as B cell lymphomas, one was a T cell lymphoma, and one was classified as polymorphic B cell hyperplasia; 5 occurred in 264 recipients of organs from living-related donors, and 4 in 388 recipients of cadaveric transplants. Fisher's exact test was used to determine whether a correlation existed between PTLD and the use of cyclosporine A, FK506, antilymphocyte therapy, or mycophenolate mofetil. A significant association between the use of mycophenolate mofetil and the development of PTLD in these patients was noted, with 8 of 481 (1.7%) patients who received this agent being diagnosed with PTLD as compared to only 1 of 221 (0.4%) patients who did not receive mycophenolate (p = .04). In comparison, no other agent was noted to be associated with the development of PTLD, with 4 of the 9 patients having received cyclosporine, 6 having received FK 506, and 4 having received antilymphocyte therapy (p > .05 for each). Although it is likely that the overall state of immunosuppression contributes to the risk for development of PTLD, these findings indicate that use of a specific agent (mycophenolate mofetil) may have been responsible for the recent increase in PTLD in kidney transplant recipients at our institution. Additional studies are warranted to determine the particular contribution of this and other immunosuppressive agents to this potentially fatal disease.