Guidelines for immunosuppression management and monitoring after transplantation in children

Abstract

There is substantial evidence for a heightened immune response in pediatric transplant recipients compared with adults. This is most important in very young children, who have a larger number of functional T cells, stronger mixed lymphocyte reactivity, and increases in some cytokine expression. Whereas corticosteroids have been the mainstay of immunosuppressive protocols for decades, many pediatric transplant programs are attempting steroid withdrawal to minimize side effects and maximize growth. Induction with polyclonal or monoclonal antibody (OKT3) therapy has been associated with improved survival and decreased rejection in many pediatric studies, particularly in renal transplant recipients. Individualized antilymphocyte dosing for children is required in many instances to overcome increased numbers of lymphocytes. In addition, particular attention to xenosensitization, infection, and malignancy is required in pediatric transplant recipients receiving antilymphocyte therapy. The introduction of cyclosporine has improved patient and graft survival in children receiving transplants. However, because of pharmacokinetic differences, increased doses and more frequent dosing intervals have been advocated, especially in the youngest children. Neoral, a new microemulsion formulation of cyclosporine, has more consistent oral absorption and pharmacokinetic predictability associated with its use. This may be particularly beneficial in pediatric transplant recipients. Tacrolimus, although similar to cyclosporine in its mechanism of action, is very appealing for use in children because of its potential steroid-sparing effects. Considerations for tacrolimus dosing parallel cyclosporine in that children frequently require increased doses compared with their adult counterparts. The recent addition of mycophenolate mofetil has not yet been extensively studied in pediatric transplant recipients; however, preliminary results are promising. Mycophenolate mofetil, an alternative to azathioprine, is associated with a lower incidence of rejection and has allowed decreased corticosteroid doses and the possibility of steroid withdrawal. These newer agents must be studied in greater detail to ascertain appropriate dosing strategies and to identify unique side effects.