TREATMENT OF ACUTE GRAFT-VERSUS-HOST DISEASE WITH MONOCLONAL ANTIBODY OKT3

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Abstract
Eight recipients of a bone-marrow graft from HLA-identical, MLR [mixed lymphocyte response]-nonreactive sibling donors who had developed grade II-IV acute graft-vs.-host disease (aGVHD), were given 14 consecutive daily injections of 5 mg of a murine anti-T-cell monoclonal antibody (MCA) called OKT3. Four patients with grade II aGVHD showed a complete response; 2 patients with grade II had a partial response, and 2 patients (1 with grade II and 1 with grade IV) showed no improvement at all. The main side effect was a high spiking fever after the 1st injection. T cells were monitored with monoclonal antibodies, indirect immunofluorescence and flow cytometry. Circulating T3+ T cells dropped to virtually 0 within 1 h following the 1st injection. Low numbers of E [erythrocyte]-rosetting cells were still demonstrable during OKT3 therapy. During the 2nd wk of treatment, T-cell markers (T3, T4, T8) started to increase again, in spite of excess antibody in the circulation. At that time, T cells showed weaker fluorescence with OKT3 than before OKT3 therapy, suggesting modulation of the T3 antigen. After cessation of OKT3 therapy, T cells reached pretreatment levels within 1 wk. None of the 6 patients studied developed anti-mouse-Ig antibodies. OKT3 therapy is probably effective in limited aGVHD. The absence of anti-mouse-Ig antibody formation may allow repeated courses of MCA that may add to their therapeutical potential.

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