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

Chronic graft-versus-host disease (cGVHD) is associated with morbidity, mortality, impaired quality of life, prolonged immunosuppressive therapy, and infection risk after allogeneic hematopoietic cell transplantation (HCT). Major strides have occurred in the understanding of cGVHD biology; National Institutes of Health Consensus meetings have refined rigorous approaches to diagnosis, staging, and response criteria; major interventional trials have established standard benchmarks for treatment outcome; and 3 agents to date have been US Food and Drug Administration approved for treating corticosteroid-refractory cGVHD. Promising results from several recent trials have led some, but not others, to conclude that the risk of developing cGVHD is sufficiently low to be considered a major post-HCT complication of the past. We propose that it is time to critically examine the results of contemporary graft-versus-host disease (GVHD) prophylaxis regimens and discuss the state of the science and associated controversies in the spectrum of conclusions reached as to the risk of cGVHD. With these data, the current cGVHD incidence can be most precisely determined, and the present and future burden of cGVHD-affected patients can be accurately modeled. Through review of existing evidence, we highlight unresolved needs and opportunities to refine best GVHD prophylaxis or preemptive therapy approaches and optimize established cGVHD therapy, and make the argument that support of preclinical and clinical research is critical in improving patient outcomes.