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Updated: Aug 13, 2026
Trans-vivo Delayed Type Hypersensitivity Assay for Antigen Specific Regulation
Published on: May 2, 2013
Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus
R Sindhi1, S Webber, R Venkataramanan
1Thomas E. Starzl Transplantation Institute, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA. sindhir@chplink.chp.edu
Insights
Sirolimus (SRL) effectively rescues pediatric transplant patients with tacrolimus (TAC) failure or toxicity. Combined SRL and reduced-dose TAC also provides adequate immunosuppression, preserving renal function and controlling Epstein-Barr virus (EBV) viremia.
Area of Science:
- Pediatric transplantation
- Immunosuppression therapy
- Pharmacology
Background:
- Tacrolimus (TAC) is a cornerstone of post-transplant immunosuppression.
- TAC failure or toxicity presents significant challenges in pediatric solid organ and bone marrow transplantation.
- Alternative or adjunctive immunosuppressive agents are needed to manage TAC-related complications.
Purpose of the Study:
- To evaluate sirolimus (SRL) as a rescue agent for tacrolimus (TAC) failure or toxicity in pediatric transplant recipients.
- To assess SRL in combination with reduced-dose TAC as primary immunosuppression.
- To analyze the impact of SRL on renal function, Epstein-Barr virus (EBV) viremia, and acute rejection rates.
Main Methods:
- Retrospective analysis of 50 pediatric transplant recipients (liver, heart, intestine, etc.).
- SRL used as rescue therapy in 42 patients due to TAC failure (recurrent rejection) or toxicity (nephrotoxicity, seizures, etc.).
- SRL combined with reduced-dose TAC as primary immunosuppression in 8 patients.
Main Results:
- SRL rescue therapy resolved indications in 33/42 patients, allowing for a 50% TAC dose reduction and improved renal function.
- SRL+TAC primary immunosuppression prevented early acute rejection in 7/8 children.
- Overall acute rejection incidence was 12% (6/50); SRL discontinuation due to adverse events occurred in 9/42 rescue patients.
Conclusions:
- Sirolimus (SRL) is a viable rescue agent for pediatric transplant patients experiencing tacrolimus (TAC) failure or toxicity.
- Combining SRL with reduced-dose TAC offers effective immunosuppression, potentially preserving renal function and mitigating EBV viremia.
- Careful monitoring for adverse events and rejection is necessary when using SRL.
Aims:
The role of sirolimus (SRL) as a rescue agent (n=42) and as a component of primary immunosuppression (n=8) was evaluated in a mixed population of 50 transplanted children receiving tacrolimus (liver: 26, heart: 5, intestinal: 5, liver-intestine: 9, lung: 1, bone marrow: 1, liver-kidney: 1, multivisceral: 1). Rescue indications for tacrolimus (TAC) failure were recurrent acute rejection and acute rejection complicating withdrawal of immunosuppression in posttransplant lymphoproliferative disorder (PTLD). Rescue indications for TAC toxicity were nephrotoxicity, pancreatitis, seizures, hypertrophic cardiomyopathy, and graft-versus-host disease.
Results:
Mean age at rescue was 11.5 years and mean follow-up was 204 (range 18-800) days. As primary immunosuppression, SRL+TAC prevented early acute rejection in 7/8 children. The indication for rescue resolved in 33/42 children. In children with TAC toxicity, this was associated with decrease in TAC doses by 50%, significant improvements in renal function, and continuing 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 of them also experienced acute rejection. Three additional children also experienced acute rejection on SRL therapy (overall incidence 6/50, 12%). Pharmacokinetic analysis in the first week of SRL administration suggested a short half-life (11.8+/-5.5 hr, n=21).
Conclusions:
SRL and reduced-dose TAC may achieve adequate immunosuppression without compromising renal function or enhancing EBV viremia significantly.
