Immunosuppression for pediatric cardiac transplantation in the modern era

With the advent of the T cell activation inhibitors such as cyclosporine, heart transplant success rates for pediatric patients have improved to the point that the initially restricted ages and indications have expanded considerably. Currently the half-life (50% still alive) for children transplanted in the early 1980s is approximately 12-14 years. Decades-long survival seems likely. Components and functions of the immune system are naïve and change during postnatal development. Maturation occurs not only in the first years of life, but well through adolescence and even into adult life. These age-dependent changes within the immune system greatly complicate any attempt to assess immune implications for the use of immunosuppression in children. Since the introduction of cyclosporine, immunosuppression regimens have been virtually unchanged through the 1990s. Recently, there have been significant new immune pharmacological agents which are now commercially available, or still in investigational stages of development. The new maintenance immunosuppressive drugs are either inhibitors of de novo synthesis of nucleotides (purines or pyrimidines), or are immunophilin-binding drugs that inhibit signal transduction in lymphocytes. The newer inhibitors of de novo nucleotide synthesis include mycophenolate mofetil, mizoribine, brequinar and leflunomide. The immunophilin-binding drugs are cyclosporine, tacrolimus and rapamycin. Antibody preparations such as ATG, ATGAM and OKT3, as well as the newer biological agents, which specifically bind to the IL-2 receptor, basiliximab and daclizumab, are discussed. The potential for biologicals which inhibit co-stimulation are also discussed. There may be dramatic changes in protocols used clinically as a result of these new agents over the next decade. The increasing understanding of the alloimmune response as well as the clinical use of these newer drugs promise even better long-term results.