Modulating graft-versus-host disease to enhance the graft-versus-leukemia effect

Graft-versus-host disease (GVHD) has been linked with a potent anti-cancer effect referred to as the graft-versus-leukemia (GVL) or graft-versus-malignancy effect. In some experimental models these processes may be distinct, but in clinical practice they are very closely linked. Induction of GVHD using donor lymphocyte infusion has been used to treat relapse after transplantation. Modulation of GVHD has been explored as a method to reduce the risk of relapse after transplantation. Methods explored include altering GVHD prophylaxis after transplant, selection of peripheral-blood stem cells, prophylactic donor lymphocyte infusion, and use of cytokines. Given the toxicity associated with GVHD, defining the balance between GVHD and induction of GVL is of critical importance in transplantation. Laboratory efforts to identify the targets of GVHD and GVL may allow for more specific and effective therapies to be developed while minimizing toxicity.