Abstract and Introduction
Abstract
Induction therapy with alemtuzumab (C-1H) prior to cardiac transplantation (CTX) may allow for lower intensity maintenance immunosuppression. This is a retrospective study of patients who underwent CTX at a single institution from January 2001 until April 2009 and received no induction versus induction with C-1H on a background of tacrolimus and mycophenolate. Those with C-1H received dose-reduced calcineurin inhibitor and no steroids. A total of 220 patients were included, 110 received C-1H and 110 received no induction. Recipient baseline characteristics, donor age and gender were not different between the two groups. Mean tacrolimus levels (ng/mL) for C-1H versus no induction: months 1–3 (8.5 vs. 12.9), month 4–6 (10.2 vs. 13.0), month 7–9 (10.2 vs. 11.9) and month 10–12 (9.9 vs. 11.3) were all significantly lower for the C-1H group, p < 0.001. There were no differences between the C-1H and no induction groups at 12 months for overall survival 85.1% versus 93.6% p = 0.09, but freedom from significant rejection was significantly higher for the C-1H group, 84.5% versus 51.6%, p < 0.0001. In conclusion, induction therapy after CTX with C-1H results in a similar 12 month survival, but a greater freedom from rejection despite lower calcineurin levels and without the use of steroids.
Introduction
One-year survival following cardiac transplantation has significantly improved over the last two decades, likely as a result of multiple factors. Although 5-year survival rates have also improved, most of the gains in survival appear in the first 6–12 months following cardiac transplantation with little change in the long-term mortality rate. These results reflect contemporary immunosuppressive strategies for which the majority of patients remain on triple-drug calcineurin-based immunosuppressive therapy 5 years posttransplantation. However, the direct, nonimmunosuppressive toxicities of chronic calcineurin and steroid use, such as hypertension, diabetes, hyperlipidemia and renal dysfunction, are well-described, pervasive and may contribute to a diminished quality of life and result in worse survival. The development of immunosuppressive strategies that allow for lower intensity maintenance immunosuppression after cardiac transplantation may diminish occurrence of these toxicities and improve outcomes. However, there are few contemporary studies evaluating such a strategy in cardiac transplantation.
Alemtuzumab (Campath-1H; Berlex, Montville, NJ) is a humanized rat monoclonal antibody directed against the CD52 antigen. CD52 is a glycoprotein expressed on the majority of lymphocytes, natural killer cells, monocytes and thymocytes, whereas it is not expressed on granulocytes, plasma cells, erythrocytes, platelets or hematopoietic stem cells. Administration of a single, 30 mg infusion of alemtuzumab results in profound lymphocyte depletion (>99%) with varying rates of cell subpopulation recovery. Although initially approved for use in chronic lymphocytic leukemia, there is a growing body of literature describing the off label use of alemtuzumab as induction therapy in kidney, kidney/pancreas, pancreas, liver, intestine and lung transplantation. With the profound and prolonged lymphocyte depletion achieved with alemtuzumab, most of these studies have utilized alemtuzumab induction to facilitate a reduction in maintenance immunosuppression either with or without calcineurin inhibitors (CNIs).
Our institutional experience with alemtuzumab in lung and heart–lung transplantation has demonstrated improved survival and a decrease in the incidence of acute rejection while allowing lower intensity maintenance immunosuppression. Given this experience as well as the experience with alemtuzumab in other solid organ transplants, we hypothesized that this approach would provide equivalent to superior results in cardiac transplantation. Thus, we began the routine use of alemtuzumab as induction therapy in association with a steroid-free maintenance immunosuppressive regimen consisting of dose-reduced tacrolimus and MMF in cardiac transplantation in October of 2006. In this study, we report the 12-month outcomes with this approach and compare them to a cohort of patients immediately preceding the study group who received standard triple immunosuppression without induction.