Strategies to prevent cellular rejection in pediatric heart transplant recipients

Abstract

Despite more than 40 years' experience in pediatric heart transplantation, cellular rejection remains a significant cause of morbidity and mortality. In this review, strategies and agents to prevent acute cellular rejection are discussed. Strategies to prevent rejection are divided into two phases - induction and maintenance therapies. Currently, the most commonly used induction agents are polyclonal antibodies (rabbit or equine antithymocyte globulin) and interleukin-2 receptor antibodies (daclizumab or basiliximab). Induction therapies have reduced early rejection, are renal sparing, and can reduce corticosteroid exposure, but have not yet been shown to have a longer term survival benefit. Multiple maintenance immunosuppressants are available. Nearly all regimens include a calcineurin inhibitor (either ciclosporin [cyclosporine] or tacrolimus). Most combinations in pediatric heart transplantation include an antiproliferative agent (azathioprine, mycophenolate mofetil or, less commonly, sirolimus). Everolimus has seen increasing use in adult heart transplant patients in Europe but, to date, its use is rare in pediatric heart transplantation. The use of corticosteroids as a third agent is still common, but strategies to avoid or minimize their use are increasing. The 'best' combination of therapies varies between studies. By gaining a better understanding of individuals' genetic and environmental risk factors, we may in the future be able to better predict the course of cardiac allografts and enhance our ability to tailor immunosuppression to individual patient variables with the ultimate goal of inducing a state of immune tolerance.