Sirolimus for pediatric liver transplant recipients with post-transplant lymphoproliferative disease and hepatoblastoma.
Sirolimus is a promising immune suppressive agent, with the potential to reduce calcineurin inhibitor associated nephrotoxicity, halt progression of chronic rejection and prevent tumor proliferation. The aim of this study was to review the experience using sirolimus in pediatric liver transplant recipients at a single center. Database and medical charts of all pediatric liver transplant recipients receiving sirolimus at the Hospital for Sick Children in Toronto were reviewed. Eight patients received sirolimus between October, 2000 and September, 2002. Indications for using sirolimus were post-transplant lymphoproliferative disease (PTLD) (n = 6) and hepatoblastoma (n = 2). Two patients with PTLD concurrently had renal impairment and chronic rejection. Sirolimus dosages ranged between 1.5 and 5 mg once daily. Median duration of follow-up was 17 months. Persistently elevated liver transaminase levels in the two children with chronic rejection decreased during sirolimus therapy. Recurrence of PTLD occurred in one patient. Two patients were diagnosed with acute cellular rejection after transition to maintenance sirolimus monotherapy. Resolution of adverse effects including mouth sores (n = 3), leg swelling (n = 2) and hyperlipidemia (n = 3) occurred either spontaneously or with dose reduction. Sirolimus was discontinued in four patients because of persisting bone marrow suppression, interstitial pneumonitis, life-threatening sepsis and refractory diarrhea. Children with PTLD or hepatoblastoma may benefit from immune suppression with sirolimus after liver transplantation. Further multi-center, prospective, randomized controlled trials will be instrumental to further the knowledge of long-term efficacy, safety and tolerability of sirolimus for selected children following liver transplantation.
Jiménez-Rivera
Carolina
C
Pediatric Academic Multi-Organ Transplant Program, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Avitzur
Yaron
Y
Fecteau
Annie H
AH
Jones
Nicola
N
Grant
David
D
Ng
Vicky Lee
VL
D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D006084:Graft Rejection; D018197:Hepatoblastoma / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D008113:Liver Neoplasms / Q000188:drug therapy*; D016031:Liver Transplantation / Q000009:adverse effects; D008232:Lymphoproliferative Disorders / Q000188:drug therapy* / Q000209:etiology; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D020123:Sirolimus