Ganciclovir Prophylaxis for Cytomegalovirus Infection in Simultaneous Kidney-Pancreas Transplant Recipients Receiving Tacrolimus, Mycophenolate Mofetil, and Prednisone A. Lo, R.J. Stratta, M.F. Egidi, A.T. Kizilisik, M.H. Shokouh-Amiri, H.P. Grewal, J. Trofe, R.R. Alloway, and A.O. Gaber T HE COMBINATION of tacrolimus (TAC), mycophe- nolate mofetil (MMF), and steroids has been shown to reduce the incidence of acute rejection in simultaneous kidney-pancreas transplant (SKPT) recipients. 1–5 However, the impact of this potent immunosuppressive regimen on cytomegalovirus (CMV) infection in SKPT recipients has not been well studied. 5–7 Due to the concern that this high intensity of immunosuppression may result in an increased risk of CMV infection, routine ganciclovir prophylaxis to all SKPT recipients at our center was instituted. The purpose of this study was to analyze the patterns of CMV infection in SKPT patients under TAC, MMF, and prednisone immunosuppression with ganciclovir prophylaxis. MATERIALS AND METHODS Seventy-five SKPT recipients transplanted at our center between January 1, 1996 and July 1, 1999 with a minimum of 6 months follow up were included in this retrospective analysis. Based on a review of inpatient and outpatient records; patient demographics including donor and recipient CMV serology, transplant and immunologic characteristics; incidence of CMV infection or CMV disease; incidence of presumed and biopsy-proven kidney and/or pancreas rejection; and patient and graft survival rates were collected and analyzed. CMV infection was defined as the isolation of CMV from a sterile site or seroconversion and CMV disease was defined as symptomatic or invasive CMV infection. 8 All patients received TAC, MMF, and steroids for maintenance immunosup- pression. Due to an evolution in our immunosuppressive protocols over the study period, 14% received anti–T-lymphocyte induction, 20% received interleukin-2 receptor antagonists, and 66% of the patients did not receive any antibody induction. All study patients received intravenous ganciclovir (2.5 mg/kg every 12 hours adjusted for renal function) during the initial hospitalization followed by oral ganciclovir therapy (1 g three times daily adjusted for renal function) for 3 months. CMV seronegative patients receiving CMV seropositive organs received 6 months of oral ganciclovir therapy. RESULTS Seventy-four patients were included in the data analysis. One patient with unknown donor serology was excluded. After a mean follow up of 23 months, patient, kidney, and pancreas graft survival rates were 86%, 84%, and 74%, respectively. The incidence of acute rejection was 38%. The incidence of CMV infection was 16 of 74 (22%), CMV syndrome 4 of 74 (5%), and tissue invasive CMV disease 7 of 74 (9%). Of the seven cases of tissue invasive CMV disease, six cases were biopsy-proven CMV gastritis/colitis and one case was CMV pneumonitis. None of the patients expired due to CMV infection. The data were then analyzed after stratification into CMV donor (D)/recipient (R) sero- logic risk groups. Sixteen of 74 patients (22%) were CMV D+/R-, 25 of 74 (33%) were CMV D+/R+, 16 of 74 (22%) were D-/R+, and 17 of 74 (23%) were D-/R-. Demographic, transplant, and immunologic characteristics were similar among groups (Table 1). As expected, the incidence of CMV infection was highest in the CMV D+/R- patients (44%) compared to none in the CMV D-/R- patients (Table 1). However, there were no signif- icant differences in patient and graft survival rates or the incidence of rejection among the four serologic groups (Table 1). Concurrent CMV infection and rejection oc- curred more frequently in the CMV D+/R- group than the other three serologic groups (25% vs 7%, P = .04). The timing of CMV infection, CMV syndrome, and CMV disease did not differ among the groups (Table 1). CMV D-/R- patients had a significantly higher incidence of event free survival (no CMV infection, no rejection, no graft loss) than the other three serologic groups combined (76% vs 33%, P = .02). Ganciclovir was well tolerated and no serious adverse events were attributed to ganciclovir during the study period. DISCUSSION Universal ganciclovir prophylaxis in SKPT patients under TAC, MMF, and prednisone immunosuppression is effec- tive in reducing the incidence and the severity of CMV infection. Our observations are in accordance with the From the Departments of Pharmacy (A.L., J.T., R.R.A.), Sur- gery (R.J.S., A.T.K., M.H.S.-A., H.P.G., R.R.A., A.O.G.) and Medicine (M.F.E.), University of Tennessee, Memphis, Tennes- see. Address reprint requests to R.J. Stratta, MD, Department of Surgery, University of Tennessee-Memphis, 956 Court Avenue, Suite A202, Memphis, TN 38163. E-mail: rstratta@utmem.edu. 0041-1345/01/$–see front matter © 2001 by Elsevier Science Inc. PII S0041-1345(00)02684-1 655 Avenue of the Americas, New York, NY 10010 1796 Transplantation Proceedings, 33, 1796–1798 (2001)