The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease

Chronic graft-versus-host disease Blood and marrow transplantation Immune mechanisms Clinical manifestationsA B S T R A C T Chronic graft-versus-host disease (GVHD) is the leading cause of late, nonrelapse mortality and disability in allogeneic hematopoietic cell transplantation recipients and a major obstacle to improving outcomes.The biology of chronic GVHD remains enigmatic, but understanding the underpinnings of the immunologic mechanisms responsible for the initiation and progression of disease is fundamental to developing effective prevention and treatment strategies.The goals of this task force review are as follows:• Summarize the current state of the science regarding pathogenic mechanisms of chronic GVHD and crit- ical knowledge gaps.• Develop working hypotheses/overriding concepts for chronic GVHD development.• Define the usefulness of current preclinical models to test working hypotheses and ultimately discover and develop new therapeutic strategies.• Identify shortcomings of preclinical models, and define criteria for the creation of additional models to address these limitations.