Guidelines for the optimal use of muromonab CD3 in transplantation

Muromonab CD3 (OKT3), the murine anti-CD3 monoclonal antibody (mAb) of the IgG-2a class, directed against the CD3 molecule on the surface of human T c ells, has proven to be a powerful immunosuppressive agent in solid organ tr ansplantation and has been shown to be superior to high-dose steroids as fi rst-line treatment of acute allograft rejection. It is comparable to antith ymocyte globulin (ATG) in treating steroid-resistant rejection and it is al so effective as rescue treatment in ATG-resistant rejection. However, OKT3 treatment is followed by a substantial percentage of re-rejections, most of which respond well to steroids. In the early post-transplant period, a pro phylactic course of OKT3 can delay the onset of acute rejection, in particu lar in immunologically high-risk patients. First-dose-related adverse effects (pyrexia, dyspnoea, headache, nausea, vo miting and diarrhoea) of OKT3 are severe, but usually transient and seldom life-threatening, provided overhydration has been corrected and steroids ha ve been given before the first administration. These adverse effects are pa rtly attributed to the release of cytokines as a result of mononuclear cell activation. In addition, complement activation and subsequent activation o f neutrophils may play a role in their pathogenesis. After exposure of pati ents to OKT3 an increased incidence of infections and malignancies has been reported. However, most likely this merely reflects the total burden of im munosuppression, Xenosensitisation represents an important limitation to OK T3 treatment, although a second or third course can still be effective in p atients with low antibody titres. In practice, the initiation of OKT3 treatment should be preceded by correct ion of overhydration, if necessary by means of dialysis or ultrafiltration. According to the instructions from the manufacturer the first dose of OKT3 is preceded by paracetamol (acetaminophen), an antihistamine and intraveno us (IV) corticosteroids. in an attempt to mitigate the first dose-related s ymptoms. A regimen consisting of administration of 2 IV doses of 250mg meth ylprednisolone, given 6 hours and 1 hour before the first OKT3 injection, f ollowed by a 2-hour infusion of OKT3, is most effective in diminishing OKT3 -induced adverse effects.