Allogeneic bone marrow transplantation is curative for some patients with hematologic malignancies. Evidence suggests that the success of transplant is related not only to high doses of chemotherapy and radiation but also to the donor's immune system and whether it mediates an antileukemia effect -- termed the graft-versus-leukemia (GVL) effect.
Our group is currently exploring clinical methods to induce the GVL effect after bone marrow transplant. We have demonstrated that by infusing selected donor CD4+ lymphocytes, we can maintain the anti-leukemia activity while reducing the incidence of graft-versus-host disease. We are now conducting studies using donor dendritic cells and donor lymphocyte infusion (DLI) in an attempt to improve the response to DLI.
We are also exploring non-myeloablative transplantation strategies to establish a platform for adoptive immunotherapy. These 'mini' transplants allow allogeneic transplantation to be performed with much less toxicity -- permitting patients of more advanced age or with other medical conditons to undergo transplantation. In addition, we are conducting studies focused on augmenting GVL after 'mini'-transplantation.