Cellular therapy: donor lymphocyte infusion

The dose escalation of chemoradiotherapy that is achievable with stem cell transplantation is often insufficient to eradicate malignancy, and an associated immune-mediated graft-versus-malignancy effect may be equally important for many diseases. The most directly compelling evidence for its presence is the efficacy of donor lymphocyte infusions in generating anti-tumor responses, particularly for relapsed chronic-phase chronic myeloid leukemia. Response rates and durability appear lower with myeloma and acute myeloid leukemia and myelodysplasia syndrome, and minimal with acute lymphoblastic leukemia. There is relatively little data on indolent lymphoid malignancies. Issues that remain to be resolved include the precise nature of the effector cells and their target antigens, the best strategies for separating graft-versus-malignancy from graft-versus-host disease (GVHD) and their effect on the durability of responses, and the role of adjuvant chemotherapy/cytokines. Similar issues surround routine combination with nonmyeloablative transplantation protocols and preliminary data suggests that GVHD may continue to provide a major obstacle.