Pretreatment of donor bone marrow with monoclonal antibody OKT3 for prevention of acute graft-versus-host disease in allogeneic histocompatible bone-marrow transplantation.

Abstract

Ten consecutive patients undergoing transplantation of bone marrow from histocompatible siblings for treatment of haematological malignancy took part in a pilot study to test the safety of in-vitro treatment of donor bone marrow with monoclonal antibody OKT3. Three male and seven female patients aged 7-34 years received concentrated bone marrow buffy-coat cells which had been incubated with OKT3 before infusion. In-vitro studies confirmed that almost all immunocompetent T lymphocytes in the bone-marrow samples were coated with OKT3 at the time of infusion. In vitro, neonatal rabbit complement inhibited the proliferation of bone-marrow T lymphocytes in samples preincubated with OKT3 to less than 4% of the mitogenic responses of the untreated bone marrow. In contrast, fresh autologous complement did not effectively lyse OKT3-treated bone-marrow cells. Infusion of OKT3-treated bone marrow was safely accomplished, and engraftment was achieved in all patients (mean 23 days). Nine of ten patients survived for more than 100 days after bone-marrow transplantation, but significant acute graft-versus-host disease (GvHD) requiring treatment with steroids developed in five of the ten. This finding suggests that further modifications for bone-marrow pretreatment will be needed to achieve effective prophylaxis against acute GvHD in histocompatible bone-marrow transplantation.