Hyperacute Graft-Versus-Host Disease

Hyperacute graft-versus-host disease (HA-GVHD) is a fulminant form of acute GVHD that develops early after allogeneic hematopoietic cell transplantation, before neutrophil engraftment ensues, and is associated with increased risk of non-relapse mortality. While incidence of HA-GVHD appears to be decreasing owing to in vivo or ex vivo T-cell depletion strategies, it still contributes with life-threatening side effects in the setting of human leukocyte antigen (HLA) mismatch or T-cell replete grafts with insufficient immune prophylaxis. Clinically, HA-GVHD presents almost always with severe skin involvement accompanied by fever, rash, diarrhea, and hepatic dysfunction. Differential diagnosis includes engraftment syndrome, adverse drug reactions, immunogenic skin reactions, and infectious exanthems. Therapeutic approaches mirror those prescribed for post-transplant acute GVHD, centered on high-dose systemic corticosteroids. Although there is no consensus on managing corticosteroid-refractory cases, ruxolitinib could be considered the therapy of choice based on data from post-engraftment GVHD. Further studies are needed to assess effectiveness of novel agents in corticosteroid-refractory HA-GVHD. The main purpose of this review is to summarize available literature on pathophysiology, incidence, risk factors, differential diagnosis, and treatment considerations for HA-GVHD. Knowledge gaps, particularly pertaining to use of post-transplant cyclophosphamide and treatment of corticosteroid-refractory HA-GVHD, are emphasized to highlight future research opportunities.