The primary focus of my research has been the development of novel strategies for performing HLA-mismatched donor bone marrow transplants and for separating the graft versus malignancy effects of transplantation from clinically significant graft versus host disease. A second aim has been to use bone marrow transplantation as a means of inducing tolerance for solid organ transplantation. We have recently developed a non-myeloablative transplant regimen in which mixed lymphohematopoietic chimerism is reliably induced. This mixed chimerism serves as a platform for subsequent adoptive cellular immunotherapy. Striking anti-tumor responses have been seen in the majority of patients with chemorefractory hematologic malignancies. This mixed chimerism has also been shown to induce donor specific allotolerance in one patient with multiple myeloma and end stage renal disease. Studies are underway to evaluate immunological reconstitution following these transplants, the specific contributions of donor and host cell populations to the multiple hematopoietic lineages, and to further define the potentially separable mechanisms of the graft versus host and graft versus malignancy responses.