This article reviews the current understanding of the pathogenesis of chronic graft-versus-host disease (GVHD) and its management. Chronic GVHD is an immune-mediated disorder that occurs in approximately 40% of patients after allogeneic hematopoietic cell transplantation. Chronic GVHD causes significant late morbidity and mortality and affects quality of life, survival and the risk of recurrent malignancy. The National Institutes of Health criteria for diagnosis and global severity were proposed in 2005, and their clinical usefulness has been validated. The new criteria distinguish acute and chronic GVHD by clinical manifestations and not by time after transplantation. Patients with chronic GVHD require prolonged immunosuppressive treatment. Glucocorticoids remain the standard initial treatment, but significant side effects support the need for less toxic treatment. Recently emerging strategies include expansion and maintenance of regulatory T cells to accelerate immunological tolerance, elimination of pathogenic B cells and autoantibodies, and inhibition of the pathways involving with fibrosis. Pharmacologic and non-pharmacologic approaches based on these strategies have been tested. Welldesigned prospective clinical trials based on the pathogenesis of the disease are warranted to evaluate candidate treatments and establish a new standard of care for patients with chronic GVHD.
2012 The Japan Society for Hematopoietic Stem Cell Transplantation