Prophylaxis and treatment of GVHD by immunosuppression

Although the conditioning given prior to transplantation is very immunosuppressive, it is not referred to as immunosuppression. Immuno-suppression designates the post transplant therapy given to reduce the immune reactivity of the graft (responsible for GVHD).

The term "immunosuppression" is used for different modalities used to prevent GVHD either as prophylaxis or treatment.

Basically two strategies are used. One is to give immunosuppressive drugs as prophylaxis. Examples are steroids, methotrexate, cyclosporin A or tacrolimus of which the latter two specifically inhibit T cells. Steroids are used to treat GVHD. Because GVHD is initiated by allogeneic T cells, a second approach is to remove the T cells from the HSC graft, a procedure that is referred to as T cell depletion.

Prophylaxis

GVHD is an inflammatory process initiated by allogeneic T cells that recognize histoincompatibilities. Conditioning (in particular TBI) profoundly damages the tissues of the patient. As a result, many cells start to secrete TNF or IL-1 (cytokine storm) which induces and sustains inflammation, increasing the severity of GVHD. Prophylaxis of GVHD may address several parameters. For instance, the recognition of histoincompatibilities by T cells may be lowered by selecting the most compatible donor or by depleting T cells from the graft. In addition, T cell activation should be inhibited during the first month after transplantation by immune suppressive drugs such as cyclosporin A, tacrolimus or methotrexate. Furthermore, in patients at high risk of GVHD, the conditioning regimen may be adapted (less TBI) to avoid the afore mentioned cytokine storm. Read more on T cell depletion ...

Treatment of GVHD

Despite prophylaxis, GVHD may occur in 20-50 % of the transplanted patients. Systemic glucocorticoids (for instance methylprednisolone 2mg/kg/day) are the drugs of choice for the initial treatment. Topical glucocorticoids can be used additionally to treat skin GVHD. Anti-lymphocyte antibodies such as anti-thymocyte globulin (ATG or ALG) may be added. There are many variations on these therapies: the afore mentioned drugs may be combined or replaced by reagents with a similar action. Obviously, the major problem are the side effects caused by the therapy that can be either a direct consequence of the drug given or of the infections caused by the profound immune suppression.