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.
Lobach
Natalia E
NE
Division of Cardiology, Department of Pediatrics and Immunology, University of Toronto, Toronto, Ontario, Canada.
Pollock-Barziv
Stacey M
SM
West
Lori J
LJ
Dipchand
Anne I
AI
D000293:Adolescent; D000367:Age Factors; D002648:Child; D002669:Child Welfare; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007231:Infant, Newborn; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy; D008297:Male; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus