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Use of polyclonal antilymphocytic preparations for prophylaxis in heart transplantation.

Polyclonal antilymphocytic preparations, heterologous antibodies to human lymphoid cells, have been administered to heart transplant recipients prophylactically in the immediate perioperative period to avert rejection. The current status of the three classes of polyclonal preparations (antilymphoblast globulins, antithymocyte globulins, and antithymocyte sera) and their clinical role for prophylaxis in heart transplantation are summarized.

Adult↗

Comparative trial of immunoprophylaxis with RATG versus OKT3.

A randomized trial of rabbit antithymocyte globulin (polyclonal) versus OKT3 monoclonal antibody prophylaxis was carried out in 82 heart transplant recipients, who, in addition, received baseline immunosuppression with cyclosporine, azathioprine, and prednisone. One-year actuarial survival was comparable between groups (95% to 98%), but the likelihood of histologic rejection within the first 30 days of transplant was more than seven times greater in OKT3 patients (0.58/patient vs 0.08/patient). Patients receiving OKT3 were more likely to have repeated episodes of rejection, and the mean time to rejection for patients receiving OKT3 was shorter (33 days) than for patients receiving rabbit antithymocyte globulin (67 days). At 120 days, while 52% of patients receiving rabbit antithymocyte globulin were free of rejection, versus 37% of the OKT3 patients, the difference was not significant. There was no difference in the incidence of major or minor bacterial or viral infection between groups, but significant hemodynamic side effects were seen after the first dose of OKT3, and aseptic meningitis developed in two OKT3 patients.

Animals↗

Prospective randomized trial of OKT3- versus horse antithymocyte globulin-based immunosuppressive prophylaxis in heart transplantation.

To compare monoclonal anti-T3-receptor antibody (OKT3) and horse antithymocyte globulin (HATG) immunoprophylaxis, 23 heart transplant recipients were randomized to OKT3 (N = 12) 5 mg IV x 14 days of HATG (N = 11) 5 mg/kg IV x 10 days and followed up for 216 +/- 137 days receiving triple immunosuppression. Recipient groups were demographically and clinically similar. First rejection occurred later in OKT3 recipients vs HATG recipients (31.7 +/- 18.3 vs 15.1 +/- 2.3 days; p less than 0.01), but the first rejection necessitating intensified immunosuppression occurred at similar times (30.9 +/- 14.6 vs 21.9 +/- 10.2 days; NS). Phenotypic characterization of peripheral blood lymphocytes by flow cytometry revealed that OKT3 and HATG recipients had similar decreases in total T lymphocytes and lymphocyte subpopulations. During the follow-up period rejection rates in the OKT3- and in the HATG-treated patients were 3.4 +/- 2.7 and 5.9 +/- 4.7, respectively (NS). The number of rejection episodes per recipient treated with intensified immunosuppression was 1.4 +/- 1.2 in the OKT3- and 2.0 +/- 3.1 in the HATG-treated patients (NS). Infection rates were 4.9 +/- 5.2 in the OKT3- and 2.7 +/- 1.7 in the HATG-treated patients (NS). The number of infection episodes that necessitated intravenous antimicrobial therapy was 2.7 +/- 2.3 in the OKT3- and 1.6 +/- 1.3 in the HATG-treated recipients (NS). The number and length of hospitalizations were similar in patients given OKT3-based or HATG-based immunoprophylaxis. We conclude that immunosuppressive prophylaxis with OKT3 vs HATG in heart transplant recipients is associated with a slightly lower incidence and severity of rejection and slightly higher infection rates.

Animals↗

Induction immunosuppression for patients bridged to transplantation.

From January 1987 through July 1989, nine patients (eight male, one female) underwent bridge to transplantation and were managed with a modified immunosuppression regimen based around the monoclonal antibody OKT3. Six patients were bridged with the Jarvik-7 70 cc total artificial heart, four patients with centrifugal ventricular assist devices, and one patient with a Novacor left ventricular assist system. In two patients two devices were used. There was one patient death at 29 days after transplantation because of acute rejection. One other patient had a rejection episode 368 days after transplantation, for an overall rejection incidence of 0.22 episodes/patient. Four infections occurred, and all were viral--three cytomegalovirus and one mumps. Posttransplant complications involving other organ systems were minimal. In follow-up, from 2 to 29 months, six patients are in New York Heart Association functional status class I and one is in class II. Six patients are not taking steroids. The serum cholesterol level in the patients not receiving steroids at 6 and 12 months is 151 +/- 11 and 171 +/- 23 mg/dl (+/- SEM), respectively. Because of these results we have expanded our indications for the modified regimen using OKT3 in patients with preoperative organ system dysfunction, in diabetic patients, in pediatric patients, in female patients, and in posttransplant patients who require mechanical assistance.

Adolescent↗

[Use of OKT-3 in treatment of rejection following kidney transplantation].

Application of OKT-3 as rescue therapy in steroid-resistant rejection was effective in 7 out of 9 patients early after cadaveric kidney transplantation. Under attention of instructions for use of OKT-3 the adverse first-dose reactions are rare. The problem of OKT-3 therapy is early use and its reuse.

Adult↗

Uses of orthoclone OKT3 for prophylaxis of rejection and induction in initial nonfunction in kidney transplantation.

We have shown that OKT3 can be safely administered to a varied group of transplant recipients, including a high percentage of diabetics and older patients. Used as a prophylactic agent, OKT3 was associated with a decreased incidence and delayed onset of acute rejection. Effectiveness may be reduced by shortening the course of treatment and/or lowering the dose of concomitant azathioprine. Use of OKT3 in patients with ATN (thereby avoiding use of CyA) may be a beneficial strategy. Stimulation of significant titers of antimurine antibody has not been a common event in this study.

Adolescent↗