Monitoring and Management of Immunosuppression in Paediatric Transplant Patients

Summary There is substantial evidence for a heightened immune response in paediatric transplant recipients when 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 expression of some cytokines. Although corticosteroids have been a mainstay of immunosuppressive protocols for decades, many paediatric transplant programmes are attempting steroid withdrawal in order to minimise adverse effects and maximise growth. Induction with polyclonal or monoclonal [muromonab-CD3 (OKT3)] anti-lymphocyte antibody therapy has been associated with improved survival and decreased rejection in many paediatric studies, especially in renal transplant recipients. Individualised dosages of antilymphocyte antibody are required in many instances for children in order to overcome increased numbers of lymphocytes. In addition, particular attention to xenosensitisation, infection and malignancy is required in paediatric transplant recipients receiving antilymphocyte therapy. The introduction of cyclosporin has improved patient and graft survival in children receiving transplants. However, because of pharmacokinetic differences, increased dosages and more frequent administration have been advocated, especially in young children. It has been suggested that a new microemulsion form of cyclosporin may have more consistent oral absorption and pharmacokinetic predictability associated with its use. This would be particularly beneficial in paediatric transplant recipients. Tacrolimus is similar to cyclosporin in its mechanism of action, and is very appealing for use in children due to its potential steroid-sparing effects. Considerations for tacrolimus administration parallel those for cyclosporin, in that children frequently require increased dosages compared with adults. Finally, new agents in development need to be studied in detail in children to ascertain appropriate dosage strategies and to identify possible unique adverse effects.