Graft-versus-host disease: why have we not made more progress?

Although allogeneic hematopoietic stem cell transplantation (allo-SCT) is potentially curative for a number of hematologic malignancies, its use is limited by the development of acute and chronic graft-versus-host disease (GVHD). This potentially fatal complication occurs in approximately 50% of allo-SCT recipients.

The pathogenesis of acute and chronic GVHD remains poorly understood, methods to prevent it are largely unchanged over the last two decades, and response to front-line treatment with corticosteroids is suboptimal. For patients with steroid-refractory disease, response to second-line treatment is dismal. The prospective clinical studies evaluating new agents for GVHD have been hampered by the inconsistencies in design, making generalization difficult, and few multicenter studies have been conducted.

Advances have been made over the last decade in grading both acute and chronic GVHD, with the development of biomarkers that provide improved prognostic information in acute GVHD and National Institutes of Health Consensus Criteria for improved grading of chronic GVHD. This, along with the broad understanding of the need to conduct prospective studies with uniform inclusion criteria and endpoints leading to multicenter studies, will hopefully lead to advancements in the prevention of GVHD in the near future.