Prophylaxis of acute GVHD: manipulate the graft or the environment?

Graft-versus-host disease (GVHD) is the immune response of donor T lymphocytes responding to the recipient's alloantigens. The cellular and cytokine mechanisms driving GVHD are now well defined and have led to several prophylactic approaches. Selective allodepletion techniques promise to prevent GVHD without causing immune deficiency provoked by global T-cell depletion. Targeted dosing of other (non-T-cells) cells in the graft – such as CD34+ progenitors, regulatory T cells, natural killer cells and mesenchymal stromal cells – can also lead to transplants designed to retain immune capability without causing GVHD. Immunosuppressive drugs such as methotrexate, cyclosporine and anti-lymphocyte antibodies are the mainstay in the prevention of GVHD and can be used in conjunction with engineered grafts to eliminate GVHD. In future it is anticipated that further refinements in targeting the elimination or suppression of the GVHD reacting T cells should be selective enough to preserve the important graft-versus-leukemia effect which contributes to the cure of malignant diseases by allogeneic stem-cell transplantation.