Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus.

Aims. The role of sirolimus (SRL) as a rescue agent (n=42) and as a compone nt of primary immunosuppression (n=8) was evaluated in a mixed population o f 50 transplanted children receiving tacrolimus (liver: 26, heart: 5, intes tinal: 5, liver-intestine: 9, lung: 1, bone marrow: 1, liver-kidney: 1, mul tivisceral: 1). Rescue indications for tacrolimus (TAC) failure were recurr ent acute rejection and acute rejection complicating withdrawal of immunosu ppression in posttransplant lymphoproliferative disorder (PTLD). Rescue ind ications for TAC toxicity were nephrotoxicity, pancreatitis, seizures, hype rtrophic cardiomyopathy, and graft-versus-host disease. Results. Mean age at rescue was 11.5 years and mean follow-up was 204 (rang e 18-800) days. As primary immunosuppression, SRL+TAC prevented early acute rejection in 7/8 children. The indication for, rescue resolved in 33/42 ch ildren. In children with TAC toxicity, this was associated with decrease in TAC doses by 50%, significant improvements in renal function, and continui ng decline in Epstein-Barr virus (EBV) viral load in PTLD patients. Serious adverse events led to discontinuation. of SRL in 9/42 rescue patients, 3 o f them also experienced acute rejection. Three additional children also exp erienced acute rejection on SRL therapy (overall incidence 6/50, 12%). Phar macokinetic analysis in the first week of SRL administration suggested a sh ort half-life (11.8 +/-5.5 hr, n=21). Conclusions. SRL and reduced-dose TAC may achieve adequate immunosuppressio n without compromising renal function or enhancing EBV viremia significantl y.