Harnessing graft-versus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy.

Allogeneic bone marrow transplantation was initially considered as a means of delivering supralethal doses of chemotherapy and total body irradiation (TBI) for the treatment of malignancy (Thomas, 1969, 1983). Many malignancies exhibit a steep dose±response relationship to chemoor radiotherapy, with higher doses producing greater cytoreduction. Bone marrow transplantation (BMT) enables the escalation of doses of many agents beyond those producing severe bone marrow toxicity. The marrow transplant was considered a supportive care modality to restore haematopoiesis. It has become clear, however, that the high-dose therapy does not eradicate the malignancy in many patients and that the therapeutic benefit of allogeneic marrow transplantation is largely related to an associated immune-mediated graft-versusmalignancy effect.