Dr. Ernie Beutler wrote an amusing “what if” chapter about the future of hematopoietic cell transplantation (HCT) for the Thomas textbook. I'd like to recapitulate his tone and approach here in the final chapter of the Chronic GVHD book edited by Pavletic and Vogelsang.

What if in the future, chronic graft versus host disease (GVHD) as we know it was a historical footnote in the remarkable developmental history of HCT? Starting from myeloablative procedures using bone marrow from human leukocyte antigen (HLA)-identical siblings, the majority of transplants in the future would use minimal chemotherapy or targeted immunosuppressive agents to achieve donor engraftment from a variety of sources. The donor selection process will focus on testing the malignant and healthy tissues of the patient and the immune cells of the donor to precisely identify the risks for recurrent malignancy, acute and chronic GVHD, and treatment-related complications. Each patient's risk profile would be determined prospectively and the most appropriate donor selected to optimize the chance for disease-free, cGVHD free survival.

After transplantation, patients would receive prophylaxis and preemptive treatment for GVHD based on biomarker studies suggesting impending risk, an approach currently practiced in 2008 for Cytomegalovirus and Epstein Barr virus reactivation. However, future interventions for GVHD are largely intended to protect end organs so that other treatments have time to delete the offending cells, block the causative cytokines, or remove the recipient signals inciting the immune response. End organ dysfunction, disability, and death attributable to GVHD are largely prevented.