Induction therapy with OKT3 in pediatric liver-transplant recipients

The goal of any posttransplant immunosuppressive regimen is to prevent allograft rejection while minimizing infectious complications. We hypothesized that sequential induction immunotherapy using the monoclonal antibody ORTHOCLONE OKT3 (muromonab-CD3) would meet these objectives effectively. We have therefore used such a protocol since July 1988 for all pediatric patients undergoing liver transplantation at Children's Hospital Medical Center of Cincinnati. Initial immunotherapy consisted of OKT3, administered preoperatively and then QD, methylprednisolone, and azathioprine. Cyclosporine was begun on POD 3-5, and OKT3 was discontinued when therapeutic cyclosporine levels were achieved for 48 hours. Rejection has not occurred throughout the lifetime of the allograft in 55% of long-term survivors. In the 28 patients who experienced rejection episodes, 71% had a single episode, 21% had two episodes, and 7% had a single episode, 21% had two episodes, and 7% had more than two. Rejection occurring after more than 120 days was invariably associated with noncompliance or subtherapeutic cyclosporine levels. The use of an OKT3-based sequential induction protocol resulted in a decreased incidence of acute rejection. Renal function was preserved, and the incidence of infection was not increased. Long-term outcome analysis of this protocol shows excellent patient survival and the near absence of late or chronic rejection.