OKT3 SERUM LEVELS AS A GUIDE FOR PROPHYLACTIC THERAPY - A PILOT-STUDYIN KIDNEY-TRANSPLANT RECIPIENTS

The use of OKT3 as prophylaxis in renal transplantation results in a r educed incidence of graft rejection and appears to have beneficial eff ects on long-term kidney graft survival. However, we and others have o bserved that patients still experience rejection during the period of OKT3 prophylaxis given at the regular 5 mg/day dose. Many of these pat ients had no circulating CD3+ cells at the time of rejection, but thei r OKT3 serum levels were distinctly low (< 500 ng/ml). This led us to adjust OKT3 doses (5 or 10 mg) daily, according to the patients' OKT3 levels, in order to maintain an OKT3 concentration of around 1000 ng/m l. In addition, patients were randomized to receive either 5 mg (group 1, n = 15) or 10 mg (group 2, n = 14) OKT3 as the initial three doses . Concomitant immunosuppression consisted of azathioprine and steroids , with the introduction of cyclosporin A on day 11. Patient survival w as 100 % after 3 months of follow-up. The intensity of OKT3 first-dose reactions was similar in both groups. Intragraft thrombosis, initiall y observed in a previous group of patients who received a fixed 10 mg/ day OKT3 prophylaxis, occurred in three patients in group 1 and result ed in two graft losses. The cumulative OKT3 dose was similar in both g roups (mean +/- SEM 98 +/- 2 mg in group 1 vs 102 +/- 3 mg in group 2) and higher than the 70 mg usually administered. Group 2 patients had higher OKT3 serum levels during the first 4 days of therapy. No correl ation could be found between patient weight and cumulative OKT3 dose ( r = 0.29). No patient in either group 1 or 2 experienced rejection dur ing OKT3 therapy. This compared favorably with an historical group of kidney recipients treated with a fixed 5 mg/day OKT3 dose, as 6 out of 32 patients in this group developed rejection (P = 0.045). The reject ion rate up to 3 months post-transplantation in pooled group 1 and 2 p atients was low (six episodes per 81 patient-months of risk exposure). We conclude that adaptation of the OKT3 dose according to daily OKT3 levels is safe and allows for excellent prevention of early graft reje ction.