Graft-versus-Ηost Disease: pathophysiology, clinical picture, prevention, and treatment

Haema 2016; 7(2): 180-190

by Despina Mallouri, Ioanna Sakellari

Department of Haematology and Bone Marrow Transplantation, Papanikolaou General Hospital, Thessaloniki, Greece

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Graft-versus-host disease (GvHD) remains the most significant cause of morbidity and mortality in allogeneic haematopoietic stem-cell transplant recipients. It is classified as acute or chronic, depending on the time of onset but also the characteristic clinical features and is attributed to the allo-reactivity of donor T-cells. Numerous causative factors have been implicated for GvHD development, but most important is the degree of HLA incompatibility between donor and recipient. The incidence of acute GVHD ranges from 10% to 80% with symptoms usually developing 2–3 weeks post transplant and chronic GvHD 30–70% of allogeneic transplant recipients surviving beyond 100 days, with a median onset of 4–6 months following stem cell transplantation. The diagnosis of acute GvHD is predominantly based on clinical findings. The skin is the most commonly involved organ at the onset of aGvHD followed by the gastrointestinal tract and the liver. Chronic GvHD is an immunoregulatory deficiency disorder and shares features of autoimmunity and immunodeficiency. Features of cGVHD resemble other autoimmune diseases such as sjögren syndrome, scleroderma, primary biliary cirrhosis and immune cytopenias. The signs and symptoms of chronic GvHD usually occur in the first 3 years post-transplant and often an acute GvHD is preceded. Any organ can be affected and can be widespread (skin, eyes, gastrointestinal tract, liver, lungs, muscles, fascia and joints) leading to debilitating consequences. Prophylaxis against GvHD while maintaining an effective graft-versus-leukemia/tumor response is of major importance for improving the transplant outcome and reducing mortality. Despite the major advances in the understanding of GvHD pathogenesis, and the introduction of new and targeted therapies, steroids still remain the gold standard of first-line therapy in both acute and chronic GvHD, producing sustained responses in 40-50% of patients. For steroid refractory GvHD, despite ongoing research, there is no clear consensus as to the best second- and third-line options, results are often unsatisfactory and the prognosis is poor.