Deoxyspergualin in lethal murine graft-versus-host disease

The beneficial effect of deoxyspergualin (DSG, NKT-01) on lethal graft-versus-host disease in mice has been studied in a major histoincompatible donor-recipient combination. Suppression of the effector mechanisms responsible for the lethal outcome in this GVHD model is also noted. This study reveals: (1) DSG has a marked potential for treatment of lethal GVHD; (2) DSG and methotrexate in combination yield longer survival times than DSG or MTX alone; (3) long-term survivors, following DSG treatment, become stable chimeras as evidenced by cell-surface analysis of spleen cells; and (4) high activity of H-2-reactive cytotoxic T lymphocytes is detected in spleens of the mice with lethal GVHD, whereas natural killer activity is only slightly increased. DSG inhibits CTL activity not only in the induction stage but also in the advanced stage of the disease. These findings indicate that DSG might be beneficial in clinical bone marrow transplantation either alone or in combination with MTX.