Graft versus host disease is caused by effector lymphocytes of the donor reacting against specific antigens of the patient.
Acute GVHD (aGVHD) is characterized by marked inflammation of the affected organs and tissues, and high- dose immunosuppression is warranted to reverse tissue damage and initiate the regeneration process. Importantly, severe aGVHD is an independent risk factor for chronic GVHD (cGVHD).
Chronic GVHD is usually more indolent in its presentation, resembles severe autoimmune diseases and, in its most severe forms, leads to tissue and organ damage with marked fibrosis. Not only is this process in itself immunosuppressive with impairment of normal thymic function, the immunosuppressive drugs prescribed to reverse the manifestations of the disease and promote tissue regeneration further increase the risk of severe infections and mortality.
The response to first-line treatment with corticosteroids is usually modest, and less than 50% of patients have adequate tissue regeneration in response to second-and third-line line treatments. Due to permanent organ damage, to the inability to regenerate with the use of current immunosuppressive treatments and the inevitable emergence of life-threatening infections, mortality is high in patients with intermediate and severe cGVHD.
There is clearly an unmet need for novel forms of treatment for both severe acute and chronic GVHD in order to regenerate normal organ function and decrease mortality.