OKT3 INDUCTION IN PEDIATRIC RENAL-TRANSPLANTATION

Twenty cadaveric renal transplant patients (mean age 12.5+/-4.8 years) received 14 days (mean 13.0+/-2.8 days) of OKT3 (mean dose 0.16+/-0.09 mg/kg) along with prednisone 0.5 mg/kg per day, azathioprine 2 mg/kg per day and cyclosporine 5 mg/kg per day which was increased to obtain therapeutic levels before the discontinuation of OKT3. Actuarial patient and graft survival were 100% and 50%, respectively, at both 1 and 5 years. Four children lost their grafts within the first 48 h. One loss was technical in origin, the remaining 3 had pathological evidence of vascular thrombosis. Of the remaining 16 children, 12 (75%) experienced rejection episodes within the first 2 months post transplant (mean 27+/-15 days). Successful reversal of early rejection episodes was achieved in 11 of 12 patients. Clinically significant cytomegalovirus infection occurred in 4 patients and resulted in graft loss in 2 patients. Circulating OKT3 levels ranging from 1,000 to 32,000 ng/ml were seen in all patients within the first 48 h. There was a rapid and total depletion of circulating CD3-positive lymphocytes in all patients. Anti-isotypic and anti-idiotypic OKT3 antibodies were assessed by enzyme-linked immunosorbent assay (ELISA), and blocking anti-idiotypic antibodies were detected by immunofluorescence inhibition assay. Positive OKT3 antibody titers were detected in 11 children by ELISA and 10 children by immunofluorescence inhibition assay. In summary, we have found that in pediatric renal transplant patients receiving OKT3 induction therapy: (1) there is a high occurrence of vascular thrombosis; (2) the incidence of early acute rejection is high; (3) the time to first rejection is not as long as that reported for adults; (4) there is a substantial rate of sensitization against OKT3; (5) despite successful reversal of early acute rejection, long-term graft survival does not appear to have been beneficially altered.