Donor leukocyte infusions in myeloid malignancies: new strategies

Donor leukocyte infusion (DLI) provides direct and potent graft-versus-leukemia (GVL) activity to treat relapse after allogeneic stem-cell transplantation. DLI is dramatically effective for relapsed chronic myelogenous leukemia (CML), but has been less effective for relapse of other myeloid malignancies. Nevertheless, most recipients of DLI for relapsed CML, and many patients with relapsed acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), will experience prolonged remissions and probable cure. Graft-versus-host disease remains the major complication of DLI. New strategies for GVL induction explore novel dosing regimens and both methods of enhancing GVL activity of donor T cells and of minimizing toxicity from graft-versus-host disease. Ultimately, the identification of the effector cells and target antigens for GVL induction will lead to the use of tumor-specific adoptive immunotherapy to both prevent and treat relapse with minimal toxicity. Although many issues remain unsettled, the potential to harness the graft-versus-leukemia activity of allogeneic donor cells provides a powerful new paradigm for the immunotherapy of cancer.