Adverse events associated with OKT3 immunosuppression in the prevention or treatment of allograft rejection

OKT3 is an effective and potent agent for the induction of immunosuppression as well as for the treatment of allograft rejection in transplant recipients. A complex set of symptoms, known as the cytokine release syndrome, occurs in almost all patients following the first dose of OKT3. This reaction is characterized by severe flu‐like symptoms involving, according to the initial randomized trial of OKT3, fever (73%). chills (57%), dyspnea (21%), chest pain and lightness (14%), vomiting (13%), nausea (11%), wheezing (11%), and tremor (10%). Symptoms usually begin 45 to 60 minutes after administration of OKT3 and last for 2 to 48 hours. Symptoms are lessened by pretreatment with corticosteroids, acetaminophen, and antihistamines. Reactions to subsequent doses of OKT3 generally are less severe and rarely occur after the first few doses. Although uncommon, severe reactions, including pulmonary edema, hypertension/hypotension, thromboses, aseptic meningitis, and seizures have occurred following administration of OKT3. Infections remain the primary cause of morbidity and mortality among patients treated with OKT3, particularly infections caused by herpesviruses. In the trial cited above, approximately 68% of OKT3‐treated patients and 65% of steroid‐treated patients developed infections within 45 days of treatment. Infection data from studies comparing various other immunosuppressive agents with OKT3 show similar rates for these agents in both induction and rejection therapy studies with no pattern of significant differences. Studies using trimethoprim‐sulfamethoxazole or acyclovir and immune globulin for prophylaxis ofPneumocystis cariniipneumonia and viral infections, respectively, have lowered the incidence of these infections. As with other potent immunosuppressive agents, OKT3 therapy has been associated with the development of malignant disorders. In an international study involving 37600 allograft recipients treated with OKT3, 154 malignancies were reported, including 142 that were classified as posttransplant lymphoproliferative disorder.