Guest Editorial: Two hits and four factors affecting the development of, or resistance to, transfusion-associated graft-versus-host disease.

Transfusion-associated graft-versus-host disease (TA-GVHD), a rare but usually fatal adverse effect of transfusion, is hypothesized here as a two-hit phenomenon: 1) predisposing "cytokine weather" irrespective of immunocompetence, plus 2) consequence of a (partial or total) one-way (donor to recipient) HLA match of viable donor T lymphocytes with proliferation potential. Since the introduction of irradiation, universal leukoreduction with third or later generation filters, and avoidance of transfusion from blood relatives, TA-GVHD has been successfully prevented in developed countries. However, potassium release from stored red blood cells is accelerated after irradiation, increasing the likelihood of hyperkalemia-associated mortality during rapid, and/or high-volume RBC transfusions, including exchange transfusions and extracorporeal circuit priming. Pathogen inactivation technologies may effectively prevent T lymphocyte replication, but have not yet been perfected for whole blood or red cell components. Protection against organ transplantation-associated GVHD (mainly from liver transplants) would likewise be improved by knowing and avoiding HLA one-way matched organ donors.