Calcineurin-Inhibitor Minimization in Pediatric Heart Transplant Recipients

Abstract

Purpose: A Calcineurin-inhibitor (CNI) minimization strategy has been applied to all pediatric heart transplant (HTx) recipients since 03/11 at our institution. Initiation of mTOR inhibitors (everolimus or sirolimus) at 4mo post-HTx with reduction in the CNI target by 40% has been used since that time. We hypothesize that a CNI minimization immunosuppression (IS) protocol leads to improved renal function at 1 & 2y post-HTx without a significant difference in graft survival or major complications. Methods: All pediatric HTx recipients surviving to 4mo post-HTx at our institution between 03/11-07/14 were included in the study. Age and sex matched subjects were selected from the preceding era (09/07-02/11) for comparison (1:1). IS regimen, renal function (eGFR), graft survival, and conditional freedom from rejection, infection, malignancy, and CAV were compared between the groups. Results: Twenty-seven subjects in each era were included. Basic demographic data (age, sex, race, blood type, pre-HTx diagnosis, and listing status) were similar between groups. At 1y post-HTx, 70% in the current era were taking mTOR inhibitors (58% sirolimus; 12% everolimus) vs. 48% in the prior era (all sirolimus). No CAV was seen in either group. There was a small, though not significant, improvement in renal function with the new protocol at 2y post-HTx (p= 0.11; Fig a), while freedom from rejection was higher in the current era (96% vs. 86% at 1y post-HTx) (p= 0.04; Fig b). Graft survival (both 100% at 1y post-HTx) (p= 0.65; Fig c) and freedom from infection (p= 0.34; Fig d) and malignancy (p= 0.99) were similar between groups. Conclusion: CNI minimization by early transition to mTOR inhibitors in pediatric heart transplant recipients appears safe, though it only trended toward improvement in renal function in short-term follow-up (1 & 2y post-HTx). Freedom from rejection was improved, while survival and other short-term complications were similar. Longer-term follow-up is needed to assess for late differences in renal function. (Figure Presented).