Allogeneic hematopoietic transplantation as adoptive immunotherapy: Induction of graft-versus-malignancy as primary therapy

An immune-mediated graft-versus-malignancy effect is important to prevent relapse after allogeneic bone marrow transplant for a range of hematologic malignancies and potentially some solid tumors. Graft-versus- leukemia (GVL) effects as seen in response to donor lymphocyte infusions have been most prominent against indolent malignancies including chronic myelogenous leukemia, chronic lymphocytic leukemia, and low-grade lymphoma. Acute myelogenous leukemia and multiple myeloma may also respond. An alternative strategy for allogeneic transplantation is to avoid the toxicity of high-dose chemoradiotherapy and use a relatively nontoxic, nonablative preparative regimen to achieve engraftment, allowing subsequent infusion of additional donor lymphocytes to mediate GVL. Fludarabine-based nonablative chemotherapy agents, using standard dose combinations, produce moderate myelosuppression but are sufficiently immunosuppressive to allow engraftment of an allogeneic hematopoietic transplant and generation of graft-versus- malignancy effects.