A 10-year experience with intravenous thymoglobuline in induction of immunosuppression following heart transplantation

Background: Intravenous thymoglobuline (125 mg a day for 3 days, Institut Merieux, France) has been used to induce immunosuppression following heart transplantation. Cyclosporine and prednisone, with and without azathioprine or mycophenolate mofetil were used as maintenance immunosuppression. Objective: The objective of the study was to determine the clinical effect of antibody induction of immunosuppression following heart transplantation. Methods: A retrospective analysis of the clinical experience at the Montreal Heart Institute. From 1988 to 1998, 163 patients were administered a 3-day course of intravenous thymoglobuline immediately following heart transplantation (Group 1). From 1983 to 1987 and during an isolated period in 1994, intravenous and oral cyclosporine was used immediately following heart transplantation in 48 patients (Group 2). Routine endomyocardial biopsies were performed in all patients and only moderate and severe rejection was treated. Results: One, 5- and 10-year actuarial survival rate averaged 85% +/- 3, 77% +/- 4 and 67% +/- 5 in Group 1 compared with 88% +/- 5, 81% +/- 6 and 76% +/- 6 in Group 2 (p = 0.5). At 1 year, the freedom rate from an episode of acute rejection averaged 43% +/- 4 in Group 1 and 30% +/- 7 in Group 2 (p = 0.03) and the freedom rate from an episode of infection averaged 44% +/- 4 in Group 1 and 31% +/- 7 in Group 2 (p = 0.2). At 1, 5 and 10 years, the freedom rate from graft coronary artery disease averaged 93% +/- 2, 68% +/- 5 and 50% +/- 7 in Group 1 compared with 93% +/- 4, 58% +/- 8 and 30% +/- 8 in Group 2 (p = 0.1) and the freedom rate from cancer averaged 98% +/- 1, 91% +/- 3 and 67% +/- 8 in Group 1 compared with 100%, 95% +/- 3 and 77% +/- 8 in Group 2 (p = 0.2). There was no side-effect related to the systemic injection of thymoglobuline. Conclusion: In a cyclosporine based protocol of immunosuppression, induction with an initial 3-day course of intravenous thymoglobuline is associated with a lower rate of acute rejection. Moreover, the risk of infection and of developing cancer is not increased whereas there was a trend towards a lower incidence of coronary atherosclerosis 5 and 10 years after transplantation.