Calcineurin Inhibitor-Free Immunosuppression in Pediatric Heart Transplantation Recipients: Sirolimus as a Primary Immunosuppressive Agent

Abstract

Purpose Sirolimus may reduce the development of coronary vasculopathy and calcineurin inhibitor (CNI)-induced nephropathy in adult heart transplant patients. We report our experience with sirolimus as a primary immunosuppressive agent in pediatric heart transplant patients. Methods and Materials We retrospectively reviewed records for all pediatric heart transplant patients for whom we attempted conversion to a CNI-free sirolimus-based regimen. Patients were treated routinely with an anti-metabolite medication in addition to sirolimus, with or without steroids. We examined records for demographics, episodes of rejection, and serum measures of renal function. Results We identified 18 patients (mean age at transplant 7.8 years, range 0.1–21 yrs, 45% female) for whom we attempted conversion to a sirolimus-based regimen an average of 39±46 months post transplant. Of these 18, 4 patients had to discontinue sirolimus due to side effects (pneumonitis, aphthous ulcers, proteinuria, and dactylitis). The remaining 14 patients (mean age at transplant 7.6 years, range 0.1–21 yrs, 43% female) were successfully converted over a period of 88±52 days to the CNI-free immunosuppressive protocol. Follow-up was available for an average of 2.7±2.6 years post-conversion. For these 14 patients, there was no significant difference between the rate of rejection while taking CNIs prior to conversion (0.21 rejection episodes per patient-year) compared to post-conversion (0 rejection episodes per patient-year). Serum creatinine was decreased from 1.0±0.6 mg/dL pre-conversion to 0.8±0.4 post-conversion, and 0.8±0.6 at latest follow-up, however this did not reach statistical significance. Conclusions In this small cohort, a CNI-free sirolimus-based immunosuppressive regimen was not associated with an increased rejection rate or change in markers of renal function. The use of sirolimus as a primary agent in pediatric heart transplant patients warrants further evaluation.