THE USE OF OKT3 FOR STUBBORN HEART ALLOGRAFT-REJECTION - AN ADVANCE IN CLINICAL IMMUNOTHERAPY

  • 1 November 1987
    • journal article
    • research article
    • Vol. 6  (6) , 324-328
Abstract
The suppression of heart allograft rejection in heart transplantation commonly employs cyclosporine, steroids, and azathioprine, or some combination thereof as baseline therapies. When severe or stubborn rejection is unaltered by these drugs, adjunctive immunotherapy is required. This article details our experience in treating difficult allograft rejections with a purified murine monoclonal antibody directed against the murine antihuman mature T cell (OKT3) lymphocyte. The inclusion criteria for use of OKT3 included severe histologically confirmed rejection (7 on a 0 to 10 scale) rejection refractory to other immunosuppressive agents (methylprednisolone, antithymocyte globulin), or contraindications toward the use of other immunosuppressive agents. From July 1985 through September 1986, 11 patients with severe rejection that was documented by histologic, biochemical, and clinical criteria were treated with intravenous OKT3. Of these patients, 10 had received orthotopic heart transplantations and one had undergone heterotopic transplantation. The mean duration of therapy was 14.4 days, with a single, average dose of 5 mg/day. Intended duration of therapy was 14 days per our protocol. Occasionally this was extended because of evidence of ongoing rejection or because of the potential toxicity of other immunosuppressive agents (i.e., cyclosporine nephrotoxicity in a patient with kidney failure). One patient demonstrated an equivocal response to the drug but experienced no side effects. In the remaining 10 patients a full course of treatment with OKT3 dramatically reversed the rejection and resulted in improved graft performance. On a standardized scale for histologic grading of rejection the average score decreased from 8.4 to 4.1 and stayed in the "mild" rejection range (0 to 4) thereafter. In addition, each patient had a daily complete blood count with differential and at least one T cell count performed to monitor lymphocyte counts. In all cases a profound reduction in peripheral lymphocyte and T cell counts occurred within hours of administration of OKT3. T cell markers were not regularly performed when OKT3 therapy was stopped. Two patients experienced opportunistic infections (oral Candida) that were not serious. One patient developed an innocuous side effect (diarrhea), and no patient required early interruption of therapy. Because it is well tolerated, easy to administer, and can be used either in addition to or in lieu of more conventional antirejection therapy, OKT3 may represent a significant advance in the treatment of patients with severe or stubborn heart allograft rejection.

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