Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying; the effect of adding mofetil to a steroid-free protocol under cover of high-dose aciclovir prophylaxis on the number of acute rejections, EBV infections and PTLDs after kidney transplantation. Methods: EBV serology was performed in 267 consecutive renal transplantations (1990-1997), All were treated with cyclosporine with an initial 10-day antilymphocyte globulin course, supplemented from September 1995 with MMF. In 208 consecutive transplantations after June 1992 aciclovir 3200 mg/day was given for 3 months posttransplantation. Results: After an observation period of up to 7 years we found that: (1) primary or reactivated EBV infection (PREBV) was correlated to acute rejection (treated with OKT3; P<0.00005) and to the incidence of PTLD (P=0.03; P=0.01, if Hodgkin's disease is included); (2) aciclovir protected against PREBV (P<0.00005) and (3) adding mofetil to the immunosuppressive protocol reduced PREBV further (P=0.0001), (4) in 78 transplantations treated with cyclosporine/antilymphocyte globulin/mofetil we observed only 10 acute rejections (P=0.0001), 10 PREBVs (P<0.00005), and no PTLDs compared with the cyclosporine/antilymphocyte globulin group (P=0.04). Conclusions: Supplemental immunosuppression with mofetil protects against acute rejection. In combination with aciclovir, there is also a reduction in the number of PREBVs, apparently as a result of both direct viral prophylaxis and better rejection control, and in the incidence of EBV-induced PTLD.