Graft versus leukemia (GVL)

The major reason why HSC transplantation can cure leukemia is the allogeneic effect of the graft that apart from causing GVHD is able to eradicate the last residual leukemic cell. This anti-tumor effect is known as Graft-versus-Leukemia (GVL)

It is difficult to distinguish GVL from GVHD. One may argue that, similar to the skin, liver and intestines, leukemic cells are just one of the preferred targets for allogeneic T cells that recognize the same recipient minor histocompatibility antigens on the organs and on the leukemic cells. The fact that many patients are cured from leukemia without clinical signs of GVHD does not necessarily mean that the two phenomena are distinct. One could easily envisage an allogeneic effect of the graft that is just strong enough to kill leukemic cells while the attack on the the skin or liver remains clinically unnoticed. The indications that GVL and GVHD are roughly the same are overwhelming. To begin with, the correlation between GVHD/GVL and risks of relapse is very strong. Furthermore, when donor and recipient are compatible for major and minor histocompatibility antigens (monozygotic twins), GVL is absent and the relapse rates are high which would not be so if the donor T cells were able to recognize tumor specific antigens on the leukemic cells. Nevertheless, it cannot be excluded that some of the donor alloreactive T cells recognize tumor specific antigens. Obviously, all conditions lowering GVHD decrease the GVL effect. As a consequence, recipients of a T cell depleted graft or patients requiring a strong immunosuppression are at higher risk of relapse. GVL might be used to treat patients in relapse even years after transplantion by infusing donor lymphocytes (DLI).