In allogeneic hematopoietic cell transplantation (HCT), the benefit of graft-versus-leukemia (GVL) effects often comes with the harm of graft-versushost disease (GVHD). In this issue of BBMT, Laport et al. [1] map a possible path toward GVL with a reduced risk of GVHD. GVL effects in humans were originally documented in observational studies by showing that the risk of recurrent malignancy was lower in patients with acute or chronic GVHD (aGVHD, cGVHD) compared with those without GVHD. Direct evidence for the potency of GVL effects came from studies showing that infusion of donor lymphocytes could induce remission in patients with recurrent or persistent malignancy after allogeneic HCT. The approach of using donor lymphocyte infusions (DLI) to treat recurrent malignancy after allogeneic HCT, however, has several limitations. First, the procedure is most effective for treatment of patients with chronic myeloid leukemia and is far less effective for treatment of other diseases. Second, the procedure is most effective when malignant cells cannot be detected and when the disease is progressing slowly, while offering little or no benefit when malignant cells can be detected or when the disease is progressing rapidly. Third, the proce