Sirolimus immunosuppression in pediatric heart transplant recipients: a single-center experience

Background: Sirolimus has been used in heart transplant recipients for treatment of rejection, alternative immunosuppression (IS). and promotion of regression and prevention of graft vasculopathy (coronary artery disease [CAD]). This study reports on our center's experience with 16 children who underwent heart transplantation. Methods: Data. were obtained by retrospective review. Results: Median age at time of review was 12.3 years (n = 16, 5.1 to 18.0 years; 9 boys, 7 girls), and at time of transplant 7.5 years (6 months to 18.0 years). Median time of sirolimus introduction was 2.7 years (1 month to 8.2 years) post-transplant. Fifteen patients were on steroids, 10 on tacrolimus (FK) and mycophenolate mofetil (MMF), 5 on FK and 1 on MMF with no calcineurin inhibitors (CNIs). The average dose,of sirolimus was 0.25 mg/kg or 7.0 mg/m(2) to maintain a target level of 5 to 15 mug/liter. Sirolimus was started for CAD in 6 patients (38%), rejection in 5 (31%), and in 5 with combinations of CNI intolerance, CAD, renal, dysfunction and rejection. All 6 who received sirolimus for rejection (International Society, for Heart and Lung Transplantation [ISHLT] Grade 3A) showed improvement on follow-up biopsies. Two of 3 who received sirolimus for renal dysfunction showed improvement (glomerular filtration rate [GFR] 43 to 67 and 32 to 106 ml/min per 1.73 m(2), respectively). Side effects included, hyperlipidemia: (38%), abdominal pain (31%), mouth ulcers (26%), anemia or neutropenia (12.5%), persistent pericardial effusion (6%) and interstitial lung disease (6%). Sirolimus therapy was discontinued in 3 patients due to side effects. Conclusions: In this study sirolimus was found, to be a valuable IS agent for the management of rejection, significant renal dysfunction and CNI side effects. These results support the need for prospective studies of the-role of sirolimus,in primary rejection prophylaxis, primary CAD prophylaxis and CAD regression. There also exists a need to establish an adverse event profile for this drug. Copyright (C) 2005 by the International Society for Heart and Lung Transplantation.