Journal
BLOOD
Volume 124, Issue 3, Pages 363-373Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2014-01-514786
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Funding
- Office of Research in Women's Health
- National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Oregon Building Interdisciplinary Research Careers in Women's Health, Award [2K12HD043488-12]
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Over the past 5 years, many novel approaches to early diagnosis, prevention, and treatment of acute graft-versus-host disease (aGVHD) have been translated from the bench to the bedside. In this review, we highlight recent discoveries in the context of current aGVHD care. The most significant innovations that have already reached the clinic are prophylaxis strategies based upon a refinement of our understanding of key sensors, effectors, suppressors of the immune alloreactive response, and the resultant tissue damage from the aGVHD inflammatory cascade. In the near future, aGVHD prevention and treatment will likely involve multiple modalities, including small molecules regulating immunologic checkpoints, enhancement of suppressor cytokines and cellular subsets, modulation of the microbiota, graft manipulation, and other donor-based prophylaxis strategies. Despite long-term efforts, major challenges in treatment of established aGVHD still remain. Resolution of inflammation and facilitation of rapid immune reconstitution in those with only a limited response to corticosteroids is a research arena that remains rife with opportunity and urgent clinical need.
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