Standard versus low‐dose OKT3 induction therapy of cadaveric renal transplants: Comparison of outcome data versus OKT3 dose and serum levels

Abstract

Lymphocytoreductive therapy with the polyclonal antithymocyte globulin or the monoclonal anti‐CD3 antibody (OKT3) has been an integral part of sequential immunosuppressive protocols. The optimum dosage of OKT3 in early posttransplant induction is unknown, although the use of lower doses of OKT3 than those used in rejection treatment have been shown to be effective in cadaveric renal transplant recipients. We compared immune monitoring data from 25 recipients of primary cadaver renal allografts receiving low‐dose (2 mg) induction with data from a retrospective cohort of 27 patients who received 5‐mg standard dose. Both groups were treated with the identical sequential quadruple‐therapy protocol. Monitoring parameters included daily CD3 measurement, and twice weekly measurements of serum OKT3 levels and anti‐OKT3 antibodies. Patient and graft survival were similar in both groups. OKT3 dosage increases due to high peripheral CD3 levels were necessary in 4 out of 27 patients receiving the 5‐mg doses and in 8 out of 25 patients receiving the 2‐mg dose (p<0.05). The mean total dose in the standard‐dose group was 48 mg (range 30‐70 mg), while the mean total dose for the low‐dose group was 23 mg (range 10‐58 mg) (p<0.05). Circulating OKT3 levels were significantly higher in the standard‐dose group of patients than in that group receiving low‐dose therapy (p<0.0l). None of the patients with low circulating OKT3 levels developed major post‐transplant infections while 5 of 15 patients with high circulating levels (>700 ng/dl) required hospitalization for bacterial (n = 3) or viral (n = 2) infections in the first 3 months posttransplant (p<0.0001). Antimurine antibodies developed in 5 (19%) of the patients receiving standard‐dose therapy while only 2 (8%) of the patients receiving low‐dose induction became sensitized. These data indicate that the success of OKT3 induction therapy is not correlated to the dosage or to the circulating levels achieved and that higher circulating levels may be associated with increased risk for infection.