The Graft-Versus-Leukemia Effect in AML

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the most established and commonly used cellular immunotherapy in cancer care. It is the most potent anti-leukemic therapy in patients with acute myeloid leukemia (AML) and is routinely used with curative intent in patients with intermediate and poor risk disease. Donor T cells, and possibly other immune cells, eliminate residual leukemia cells after prior (radio)chemotherapy. This immune-mediated response is known as graft-versus-leukemia (GvL). Donor alloimmune responses can also be directed against healthy tissues, which is known as graft-versus-host disease (GvHD). GvHD and GvL often co-occur and, therefore, a major barrier to exploiting the full immunotherapeutic benefit of donor immune cells against patient leukemia is the immunosuppression required to treat GvHD. However, curative responses to allo-SCT and GvHD do not always occur together, suggesting that these two immune responses could be de-coupled in some patients. To make further progress in successfully promoting GvL without GvHD, we must transform our limited understanding of the cellular and molecular basis of GvL and GvHD. Specifically, in most patients we do not understand the antigenic basis of immune responses in GvL and GvHD. Identification of antigens important for GvL but not GvHD, and vice versa, could impact on donor selection, allow us to track GvL immune responses and begin to specifically harness and strengthen anti-leukemic immune responses against patient AML cells, whilst minimizing the toxicity of GvHD.