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Monotherapy with cyclosporine for chronic immunosuppression in pediatric liver transplant recipients
S P Dunn1, K Falkenstein, J P Lawrence
1Department of Surgery, St. Christopher's Hospital for Children, Temple University School of Medicine, Philadelphia, Pennsylvania 19134.
Insights
Pediatric liver transplant recipients can often transition to cyclosporine monotherapy, reducing long-term immunosuppression side effects. This approach improves growth and maintains normal liver function in most children.
Area of Science:
- Pediatric Hepatology
- Transplantation Immunology
- Immunosuppression Management
Background:
- Pediatric liver transplant (LT) survivors face lifelong immunosuppression challenges.
- Minimizing adverse effects of immunosuppression is crucial for long-term pediatric LT outcomes.
- Chronic immunosuppression can impede growth and increase morbidity in pediatric LT recipients.
Purpose of the Study:
- To evaluate the safety and efficacy of tapering immunosuppression in pediatric liver transplant recipients.
- To assess the feasibility of achieving chronic monotherapy with cyclosporine post-LT.
- To determine the impact of reduced immunosuppression on patient growth and graft function.
Main Methods:
- A retrospective analysis of 73 pediatric liver transplant recipients (ages 4 months to 19 years) between 1987 and 1992.
- Implementation of a tapering protocol for prednisone and azathioprine, aiming for cyclosporine monotherapy.
- Monitoring of patient and graft survival, liver function tests, growth parameters, and rejection episodes.
Main Results:
- Patient survival was 85% and graft survival was 73% at one year post-LT.
- Of 37 eligible survivors, 28 (76%) were tapered to monotherapy, with 25 (89%) remaining on it long-term (average 2 years).
- 66% of children below the 5th percentile for height improved post-monotherapy; 3 patients (11%) experienced rejection, linked to factors affecting cyclosporine levels.
Conclusions:
- The majority of stable pediatric liver transplant recipients can be safely transitioned to chronic cyclosporine monotherapy.
- Reduced steroid dosing significantly improves growth in pediatric LT recipients.
- Maintaining adequate cyclosporine levels is critical for the success of monotherapy and preventing rejection.
Abstract:
Children who survive liver transplantation (LT) suffer the adverse effects of life-long immunosuppression. In an attempt to minimize these effects, we have instituted a program of tapering immunosuppression, resulting in chronic monotherapy for children after LT. Seventy-three children ages 4 months to 19 years received LT between January 1987 and December 1992. Patient survival was 85% (62/73), with graft survival of 73%, at one year. Triple therapy with prednisone, cyclosporine, and azathioprine begun at transplant was tapered as follows: 1-2 mg/kg prednisone at discharge was reduced by .2 mg/kg every 2 months until a .2 mg/kg total was reached. Alternate-day steroids (.2 mg/kg) were begun at 1 year and discontinued at 1.5 years. AZA (1 mg/kg) was begun posttransplant and discontinued after any serious viral illness or by 1 year. Currently 37 survivors are > 18 months post-LT and were considered candidates for monotherapy. Monotherapy was attempted in 28 (76%), and 25 of these remain on monotherapy an average of 2 years later. All have normal liver function. After monotherapy and alternate-day steroids were achieved, 66% of children < 5th percentile for height at the time of transplant improved to greater than the 5th percentile. There were 3 (11%) patients who rejected while on monotherapy an average of 1.15 years after it was started. These patients had the following predisposing factors that decreased cyclosporine levels and led to rejection: common bile duct stricture, chronic and intermittent antibiotic administration for urinary tract infection, and noncompliance. In the 9 potential candidates not tapered to monotherapy, 6 have had recurrent acute or chronic rejection; 2 of these now receive FK506. We conclude that the majority of stable pediatric LT recipients may be safely tapered to chronic cyclosporine monotherapy. Increased growth is a major benefit of decreased steroid dosing in these children. Cyclosporine absorption and adequate levels are crucial for success of this approach.