From the Department of Haematology, Royal Free and University College London School of Medicine, London, United Kingdom
Author's disclosure of potential conflicts of interest is found at the end of this article.
Address reprint requests to Stephen Mackinnon, MD, Department of Haematology, Royal Free and University College London School of Medicine, Pond Street, London NW3 2QG, United Kingdom; e-mail: s.mackinnon{at}ucl.ac.uk
Overview: There is a strong graft-versus-leukemia/lymphoma (GVL) effect after allogeneic stem cell transplantation (SCT) mediated by T cells of donor origin. This antitumor effect is seen in some diseases, such as chronic myeloid leukemia (CML), after standard myeloablative conditioning and is enhanced by chronic graft-versus-host disease (GVHD). This GVL activity is more important after nonmyeloablative or reduced-intensity conditioning SCT, in which the chemoradiotherapy is less likely to eliminate residual disease. The most directly compelling evidence for the presence of GVL has been provided by the efficacy of donor lymphocyte infusions (DLI) in generating antitumor responses, particularly for relapsed chronic-phase CML. Response rates and durability appear lower with myeloma, acute myeloid leukemia, and myelodysplastic syndromes and minimal with acute lymphoblastic leukemia. More recently, data suggest that indolent lymphoid malignancies may have durable responses to DLI after reduced-intensity SCT, although longer follow-up is required to determine whether this results in a long-term cure. The precise nature of the effector cells and their target antigens, the best strategies for separating GVL from GVHD and their effect on the durability of responses, and the role of adjuvant chemotherapy/cytokines remain to be resolved.
