Induction of immunosuppression in pediatric orthotopic liver transplantation

This report reviews our experience with prophylactic OKT3 in pediatric liver transplantation, induction protocols in use elsewhere, and future new alternatives. In a randomized prospective study we have compared induction with OKT3, steroids and azathioprine to conventional therapy with cyclosporine, steroids and azathioprine. Twelve children were in the OKT3 prophylaxis group and 8 in the cyclosporine group. In the first 14 days patients in the OKT3 group had significantly less rejection (25%) compared to the cyclosporine group (75%). A high incidence of rebound rejection (33%) was seen in the OKT3 group so that overall there was no difference in rejection incidence between the two groups (83% in OKT3 group, 87% in cyclosporine group). The OKT3 group did not have an increased risk of infection. Long-term follow-up showed no difference in graft or patient survival, renal function, or the late occurrence of rejection or infection. On recommended doses of OKT3, 45% of children were unable to maintain CD3+ cells less than 5%. Sixty-seven percent of children developed anti-OKT3 antibodies after prophylaxis, usually of low titer. OKT3 was re-used after prophylaxis for treatment of 7 rejection episodes. Two-thirds of these patients developed CD3+ cells greater than 60%. Two episodes completely resolved and 3 partially responded. Compared to adults in the same study, pediatric recipients had more rejection requiring OKT3 rescue,a higher incidence of increased CD3+ cells during OKT3 use, and developed anti-OKT3 antibodies more often. Pediatric patients require careful monitoring during OKT3 use and may require higher doses than currently used. As OKT3 prophylaxis offered no long-term benefits, we reserve its use for treatment of steroid-resistant rejection. OKT3 prophylaxis is indicated in carefully selected patients in whom intravenous cyclosporine is contraindicated.