Allogeneic hematopoietic stem cell transplantation (alloSCT) can produce durable remissions in many patients suffering from hematologic malignancies. The elimination of malignant cells after the transplant was initially thought to be attributable to the myeloablative chemotherapy and irradiation administered during the procedure, and infusion of hematopoietic stem cells was necessary to restore normal hematopoiesis. Autologous hematopoietic cell grafts or grafts derived from an identical twin were felt to provide the optimal source of hematopoietic stem cells for transplantation, because the use of grafts from allogeneic donors was associated with immunologic complications including severe graft-versus-host disease (GVHD). However, the development of GVHD was associated with a decreased likelihood of posttransplant relapse—leading to the concept of a graft-versus-leukemia (GVL) effect. Depletion of T cells from the hematopoietic cell graft decreased the risk of GVHD, but was also associated with an increased risk of posttransplant relapse, suggesting that T cells play a crucial role in the development of both GVHD and GVL. Moreover, transplantation with a T cellreplete graft from an identical twin was not associated with a significant GVL effect, demonstrating that the mere presence of T cells in hematopoietic stem cell grafts is not sufficient to mediate GVL activity, and that genetic disparity between donor and recipient is required for a significant antitumor effect. Durable remissions of persistent or relapsed leukemia after donor lymphocyte infusion (DLI) provided direct evidence for a GVL effect mediated by donor

T cells [1]. DLI can produce complete remissions in 20% to 80% of patients, with the success rate highly dependent on the underlying malignancy. Chronic myeloid leukemia (CML) in chronic phase is highly susceptible to DLI. Although the success rate is much lower, and additional chemotherapy and/or antibody administration may be required in patients with other hematologic malignancies, patients treated for relapsed acute myeloid leukemia (AML), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), or non-Hodgkin’s lymphoma (NHL), and some patients with acute lymphoblastic leukemia (ALL), may also show profound clinical responses. The striking therapeutic efficacy of DLI demonstrated unequivocally that donor-derived T cells recognizing alloantigens on the recipient’s tumor cells can mediate curative GVL reactivity.