The use of OKT3 for stubborn heart allograft rejection: an advance in clinical immunotherapy?

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.(ABSTRACT TRUNCATED AT 250 WORDS)