Acute Graft‐versus‐Host Disease: Emerging Insights and Updates into Detection, Prevention, and Treatment

Abstract

Acute graft‐versus‐host disease remains a devastating complication following hematopoietic cell transplantation, resulting in increased morbidity and mortality. Vast research efforts continue to refine or develop new means of prediction, assessment, prevention, and treatment of this syndrome. Recent updates in acute graft‐versus‐host disease include more definitive guidance and definitions for its grading and diagnosis. Biomarker use is being incorporated into early stages following hematopoietic cell transplantation to aid in the detection and prediction of long‐term outcomes. New preventive strategies under investigation include the use of vedolizumab or tocilizumab as upfront prophylaxis. Finally, although steroids remain the backbone of therapy once treatment is warranted, the efficacy of several agents including vedolizumab, tocilizumab, ruxolitinib, and α1 antitrypsin are being evaluated as potential therapeutic options.

Gut Microbiota Influence in Hematological Malignancies: From Genesis to Cure

“…The graft additionally contains allogeneic T-cells, which can attack residual malignant cells (graft vs. tumor effect) or healthy host tissues (graft vs. host disease (GvHD)) [100]. GvHD is still a leading cause of morbidity and mortality [101,102]. Acute GvHD (aGvHD) occurs in about 30-50% of patients and classically develops within 100 days after transplantation; however, late-onset aGvHD may develop even later [103].…”

“…Phase 1 is characterized by tissue damage due to a conditioning regiment that causes release of inflammatory cytokines and activation of host antigen-presenting cells (APC). During the second phase, host and donor APCs activate lymphocytes to produce Th1 cytokines and in phase 3, T cells migrate to target tissues and produce direct damage, especially in the skin, the gut and the liver [102,104]. Chronic GvHD (cGvHD) can occur with or without previous aGvHD and occurs in approximately 40% of patients [103].…”

Acute Graft-Versus-Host Disease, Prophylaxis and Therapy

“…Cytokines are among the critical effector molecules involved in GVHD pathogenesis and their kinetic pattern of expression is different in various affected tissues [127]. Newer agents that target GI GVHD such as tocilizumab, vedolizumab, alpha-1 antitrypsin and itacitinib are being explored with small prospective and retrospective studies showing varying responses based on organ involvement [128][129][130][131][132]. It remains to be seen whether these or other strategies will have a significant benefit on the long-term outcomes of GI GVHD.…”

“…It remains to be seen whether these or other strategies will have a significant benefit on the long-term outcomes of GI GVHD. These agents were discussed in detail in a recent publication in pharmacotherapy [130].…”

Evolution and Innovation in Hematopoietic Cell Transplantation and Cellular Immunotherapy: Critical Updates in Therapeutics

“…response rates and duration are suboptimal and thus the search to better comprehend GVHD pathophysiology and uncover more efficacious therapeutic management strategies is ongoing. In their companion articles found in this issue, DiMaggio, 5 Gonzalez, and Pidala, 6 provide concise reviews of the current thinking on acute and chronic GVHD with respect to pathophysiology, staging and classification systems, biomarkers, and new agents being evaluated for the prevention and treatment of GVHD. As their reviews demonstrate, large strides have been made in the understanding of this complication with resultant improvements in responses to therapy and, in some cases, even GVHD-free survival, compared with traditional therapies.…”