Organ siderosis and hemophagocytosis during acute graft-versus-host disease

Iron overload prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to blood transfusions is associated with increased non-relapse mortality (NRM) and with low overall survival.1,2 After allo-HSCT, high iron content in liver biopsies and elevated ferritin concentrations in blood, used as a surrogate parameter for iron overload, are also related to NRM.3–6 The cellular and molecular mechanisms behind this association, however, are yet to be clarified. In particular, available data on the role of ferritin and iron metabolism during the pathophysiology of acute graft-versus-host disease (GvHD), a major contributor to NRM, are scarse. To shed light on the connection between GvHD, ferritin levels, and iron metabolism, we decided to analyse the clinical data of patients undergoing allo-HSCT as well as data from preclinical murine GvHD models.