Graft versus Leukemia
Graft versus Leukemia
Allogeneic hematopoietic cell transplantation is currently used to cure patients with a variety of leukemia and lymphomas. A major mechanism of cancer eradication is from the immunological-based recognition of residual host tumor cells by donor-derived immune cells contained in the donor graft. This phenomenon is termed Graft-versus-Leukemia/Lymphoma (GvL) response.
Major advances have been made by reducing the toxicity of transplantation with non-myeloablative conditioning regimens, and by facilitating the rapid engraftment of hematopoietic progenitor cells by switching from bone marrow grafts to granulocyte-colony stimulation factor (G-CSF)“mobilized” peripheral blood progenitor grafts.
When non-myeloablative conditioning is used, then eradication of tumor cells is mediated predominantly by the donor T cells in the graft that generate graft versus tumor (GVL) activity. T cell depletion of grafts results in decreased GVL activity with increased rates of tumor relapse as well as increased rates of severe infections due to immunodeficiency. The most direct evidence for the GVL effect was the observation that some patients with recurrent disease were successfully returned to complete remission after receiving donor leukocyte infusions (DL
Anti-leukemic responses in patients are mainly associated with conversion to full donor chimerism. However, the response rate of DLI varies in various hematologic malignancies. Efforts to improve the response rates while reducing the associated treatment-related mortality (Graft versus Host Disease) is an active area of preclinical investigation.
My research intends to improve therapeutic efficacy of DLI in relapsed B cell lymphoma following non-myeloablative bone marrow transplants through infusion of donor memory phenotype CD8+ T cells.
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