Prophylaxis of Cytomegalovirus Disease in Mismatched Patients after Heart Transplantation Using Combined Antiviral and Immunoglobulin Therapy L.S.C. Czer, A. Ruzza, R. Vespignani, M. Rafiei, J.R. Pixton, M. Awad, M. De Robertis, A.V. Wong, and A. Trento ABSTRACT Background. Cytomegalovirus (CMV) is a common cause of infection and morbidity after heart transplantation. Seronegative recipients (R-) of seropositive donor hearts (D+) are at high risk for CMV disease. We compared three different CMV prophylaxis regimens using combined antiviral and immunoglobulin therapy. Methods. In 99 patients who survived more than 30 days after heart transplant, all received induction with antilymphocytic therapy and triple-drug therapy. In group A, D+R- patients received one dose of intravenous immunoglobulin (IVIG) followed by one dose of CMV-specific immunoglobulin (CMV-IVIG), and intravenous ganciclovir (GCV) for 4 weeks followed by 11 months of oral acyclovir (ACV). In group B, D+R- patients received one dose IVIG followed by five doses of CMV-IVIG and intravenous GCV for 14 weeks followed by 9 months of oral ACV. In group C, D+R- patients were treated with the same regimen as for group B, except oral ACV was replaced with oral GCV. Results. The actuarial freedom from CMV disease for D+R- patients at 1 month, 1 year, and 2 years after transplantation in group A was 100%, 25%  15%, and 25%  15%, respectively; group B was 100%, 67%  27%, and 67%  27%; group C was 100%, 83%  15%, and 83%  15% (P  .01, groups B and C vs group A). By comparison, the actuarial freedom from CMV disease for seropositive recipients (D-R+ or D+R+) at 1 month, 1 year, and 2 years in group A was 100%, 87%  7%, and 82%  8%, respectively; group B was 100%, 88%  8%, and 75%  11%; group C was 100%, 72%  9%, and 72%  9% (P = NS among groups). Rejection rates did not differ among the three groups. Conclusions. A longer course of intravenous GCV with multiple doses of CMV-IVIG was a more effective prophylaxis regimen against CMV disease for the high-risk group of seronegative recipients of seropositive donor hearts. C YTOMEGALOVIRUS (CMV) infection is the major cause of infectious morbidity and mortality after solid organ transplantation. CMV transmission can occur with transplantation of a seropositive donor organ or can result from blood product transfusion during transplantation. CMV disease can also result from reactivation of a dormant virus in a previously infected recipient. The use of antilym- phocyte preparations for induction immunosuppression af- ter transplantation may increase the risk of CMV infection. CMV infection in heart transplant recipients is associated with an increased incidence of allograft rejection, graft atherosclerosis (allograft vasculopathy), and death. 1 CMV infection can also lead to host immunosuppression and predispose the patient to opportunistic infections such as fungal and parasitic infections. In one study, CMV disease was associated with significantly decreased survival, with a From the Divisions of Cardiothoracic Surgery and Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California. Address correspondence to Lawrence S. C. Czer, MD, Cedars- Sinai Medical Center, 8700 Beverly Blvd, Room 6215, Los Angeles, CA 90048. © 2011 by Elsevier Inc. All rights reserved. 0041-1345/–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2011.01.189 Transplantation Proceedings, 43, 1887–1892 (2011) 1887