OKT3 Induction Therapy Research Articles

A RANDOMIZED CLINICAL TRIAL OF INDUCTION THERAPY WITH OKT3 IN KIDNEY TRANSPLANTATION

A randomized, prospective multicenter trial was conducted to compare the safety and efficacy of OKT3 as an induction therapy with that of conventional immunosuppressive therapy administered to cadaveric renal allograft recipients. Two hundred fifteen patients were treated either with OKT3 plus azathioprine and steroids for 14 days with the delayed addition of cyclosporine on day 11, or with conventional immunosuppression (steroids, azathioprine, and cyclosporine). OKT3 patients had significantly fewer rejection episodes (51% vs. 66%, P = 0.032), a longer time to initial rejection (46 days vs. 8 days, P = 0.001), and fewer rejection episodes per patient (0.82 vs. 1.14, P = 0.014) than conventionally treated patients. Kaplan-Meier estimates of two-year graft and patient survival rates were 84% and 95%, respectively, for the OKT3-treated group, and 75% and 94%, respectively, for the conventionally treated group. Following a subsequent first rejection episode, OKT3 reversed 93% of the rejections in patients receiving OKT3 induction therapy and 94% in patients receiving conventional therapy. Adverse experiences reported during OKT3 induction therapy were similar to those seen when the drug was used for rejection. Following initial exposure, 40.3% of the patients tested were positive for anti-OKT3 antibody, only 6.7% of which were of high titer (1:1000). In the presence of low titer (1:100 or less) antibody, OKT3 was successful in reversing rejection in five of six retreated patients tested. In conclusion, treatment with OKT3 (in combination with azathioprine, steroids, and the delayed addition of cyclosporine) is an effective approach for renal allograft maintenance.

OKT3 antibody formation after OKT3 induction therapy: [formula omitted], PK Hennessy, RJ Tesi, The Ohio State University Department of Surgery, Columbus, OH

OKT3 antibody formation after OKT3 induction therapy: [formula omitted], PK Hennessy, RJ Tesi, The Ohio State University Department of Surgery, Columbus, OH

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

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.

Experience With 100 Consecutive Simultaneous Kidney-Pancreas Transplants With Bladder Drainage

From December 1985 to December 1989, 100 consecutive simultaneous pancreas-kidney (SPK) transplants were performed at the University of Wisconsin Hospital and Clinics. Bladder drainage technique was used for all grafts. One- and three-year patient survival was 93% and 90%; kidney survival, 90% and 85%; and pancreas survival, 86% and 84%. Quadruple immunosuppressive therapy was used in all patients and consisted of either MALG or OKT3 induction, and cyclosporine, prednisone, and azathioprine maintenance therapy. OKT3 induction therapy was used in 42 patients and Minnesota antilymphocyte globule in 58 patients, with equivalent results except for more opportunistic infection with OKT3. The duodenal button technique was used in the first 17 patients with systemic anticoagulation and was associated with significantly more postoperative bleeding and infection compared with the duodenal segment technique. The most common surgical complication of the duodenal segment technique was urine leak (13%), which usually occurred from the distal duodenal segment. The most common urologic complication of bladder drainage was hematuria (13%), which was usually self-limited. Within 6 months of transplantation, 84% of patients developed urinary tract infections, and 25% of patients had opportunistic infections. The surgical techniques and immunosuppressive methods used in this series are reviewed, and strategies for preventing medical and surgical complications are outlined.

Differing cellular infiltrates on serial biopsy of heart allograft recipients randomized to okt3 or hatg induction therapy: Implications for graft injury

Differing cellular infiltrates on serial biopsy of heart allograft recipients randomized to okt3 or hatg induction therapy: Implications for graft injury