Ex vivo T cell depletion with immunotoxins in allogeneic bone marrow transplantation: The pilot clinical study for prevention of graft-versus-host disease

Following extensive preclinical studies which identified potent combinations of immunotoxins for the specific inactivation of normal immunocompetent T cells, we began phase I clinical trials with this combination of reagents for ex vivo marrow cleansing as GVHD prophylaxis in allogeneic transplantation. To date, these clinical trials confirm the safety of ex vivo purging with immunotoxins and suggest that severe GVHD may be eliminated with this method in the matched transplant setting. We plan to proceed to comparative trials in order to investigate the clinical efficacy of this technique. Patients with histocompatible siblings will be randomized to receive either immunotoxin pretreatment or standard (Minnesota) in vivo GVDH prophylaxis. This approach will permit comparison of time to engraftment, posttransplant complications, GVDH rates, survival, and impact on immunoreconstitution.