Infections in patients receiving OKT3 monoclonal antibody for cardiac rejection: results of a small clinical trial.

Orthoclone OKT3 (muromonab-CD3), a murine monoclonal antibody that virtually eliminates circulating T cells and inhibits medullary lymphocyte function, has recently been found effective in reversing stubborn severe allograft rejection after heart transplantation. To determine the influence of OKT3 therapy on the development of infections in cardiac allograft recipients, we compared the frequency and severity of infection in 16 patients who underwent treatment for cardiac allograft rejection at our institution from July 1985 through November 1986. these included 11 patients on OKT3 therapy and 5 patients on a conventional immuno-suppressive regimen. With 2 exceptions late in the trial, OKT3 was used only as a rescue therapy, for patients who did not respond to standard adjunctive therapy consisting of high doses of corticosteroids or antithymocyte globulin, or both. The 5 patients who did not receive OKT3 responded to adjunctive therapy and were in general not as ill as the OKT3 recipients. Our protocol specified that patients in both groups be studied during the 6 weeks (42 days) immediately following transplantation. During this period of study, 6 patients in our 11 member OKT3 group experienced 25 infectious processes, 22 of which occurred in only 3 patients and 14 of which were considered life-threatening (2 of the 3 very ill patients died during the study period). These infections were found most often in the gastrointestinal and genitourinary tracts, involved both bacterial and nonbacterial pathogens, and developed about 2 weeks after the initiation of therapy. By comparison, 2 patients in our 5-member non-OKT3 group experienced 3 infectious processes during the study period, and these were not life-threatening. Because of the occurrence in the OKT3 group of 22 of the 25 infections in only 3 patients, these early results were skewed, but a trend was noted towards a higher incidence of bacterial infection in the OKT3 group. A larger and longer-term trial is under way to evaluate the trend.