Chronic graft-versus-host disease: Unresolved complication or ancient history?

Chronic graft-vs.-host disease (GVHD) is associated with morbidity, mortality, impaired quality of life, prolonged immunosuppressive (IS) therapy, and infection risk after allogeneic hematopoietic cell transplantation (HCT). Major strides have occurred in the understanding of chronic GVHD biology, NIH Consensus meetings have refined rigorous approaches to diagnosis, staging and response criteria, major interventional trials have established standard benchmarks for treatment outcome, and three agents to date have been FDA-approved for treating steroid-refractory chronic GVHD. Promising results from several recent trials have led some but not others to conclude that the risk of developing chronic GVHD is sufficiently low to by-and-large be considered a major post-HCT complication of the past. We propose that it is time to critically examine the results of contemporary GVHD prophylaxis regimens and discuss the state-of-the-science and associated controversies in spectrum of conclusions reached as to the risk of chronic GVHD. With these data, the current chronic GVHD incidence can be most precisely determined, and the present and future burden of chronic GVHD-affected patients be accurately modeled. Through review of existing evidence, we highlight unresolved needs and opportunities to refine best GVHD prophylaxis or preemptive therapy approaches, optimize established chronic GVHD therapy, and make the argument that support of preclinical and clinical research is critical in improving patient outcomes.