DACLIZUMAB PROVIDES SUPERIOR IMMUNOSUPPRESSION FOR PEDIATRIC RENAL TRANSPLANTS

Abstract

170 Background-Renal transplantation in children has a higher incidence of rejection than in adults. Daclizumab is a humanized mAb that binds to the high-affinity IL-2 receptor expressed on alloantigen-reactive T lymphocytes. It has been shown to reduce the frequency of acute rejection in adult recipients of primary kidney transplants. In this study the results of the use of daclizumab induction in pediatric primary renal transplants at a single institution is presented. Methods-A retrospective review of 27 consecutive pediatric renal transplant patients (mean age 10 yrs, range 4 to 18) who received daclizumab induction therapy was performed. Daclizumab (1 mg/kg, IV) was administered pre-operatively and every two weeks post-operatively for a total of 5 doses. Patients also received maintenance immunosuppression consisting of cyclosporine or tacrolimus, mycophenolate mofetil or azathioprine, and corticosteroids. The median duration of follow-up was 11 months (range 1 to 21). The primary endpoint was the incidence of biopsy proven acute rejection at 6 months and overall graft survival. Values are reported as median or mean ± SD. Results-Donors were living related in 14 of the 27 patients (52%), cadaveric in 10 (37%), and living unrelated in 3 (11%). All patients in whom rejection was suspected underwent biopsy and three of these had biopsy proven rejection by 6 months (13%). One of these had a reduction in immunosuppression because of a polyoma virus infection of the kidney. The mean time to rejection was 60 ± 19 days. Two of the three patients with acute rejection were treated with steroid pulse only. One patient was treated with a 10 day course of OKT3 and steroids. The median time to initiation of calcineurin inhibitors was 0 days (range 1 to 11). The mean serum creatinine was 0.9 ± 0.6, 0.8 ± 0.4, 0.9 ± 0.5, and 1.0 ± 0.5 at 3, 6, 9 and 12 months, respectively. Near complete binding of the IL-2Rα was demonstrated beyond 3 months by FACS. Delayed graft function occurred in one patient. There was one case of polyoma virus infection in the transplanted kidney diagnosed at 2 months. There was one case of systemic sepsis, which occurred one month following transplantation. There were no cases of lymphoproliferative disease. Overall graft survival was 100%. Conclusions-Induction therapy with daclizumab followed by maintenance triple immunosuppression markedly decreases the incidence of acute rejection at 6 months in pediatric renal transplant patients when compared to NAPRTCS data. This data suggests that dacluzimab may be an effective induction immunosuppressive agent for pediatric renal transplant.