Treatment of acute graft-versus-host disease with monoclonal antibody OKT3. Clinical results and effect on circulating T lymphocytes.
Eight recipients of a bone-marrow graft from HLA-identical, MLR-nonreactive sibling donors who had developed grade II-IV acute graft-versus-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; two patients with grade II had a partial response, and two patients (one with grade II and one with grade IV) showed no improvement at all. The main side effect was a high spiking fever after the first injection. T cells were monitored with monoclonal antibodies, indirect immunofluorescence, and flow cytometry. Circulating T3+ T cells dropped to virtually zero within 1 hr following the first injection. Low numbers of E-rosetting cells were still demonstrable during OKT3 therapy. During the second week 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 one week. None of the six patients studied developed anti-mouse-Ig antibodies. These results suggest that OKT3 therapy is 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.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D007951:Leukemia, Myeloid / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal