Iron Overload in Myelodysplastic Syndromes: Pathophysiology, Consequences, Diagnosis, and Treatment

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic neoplasms varying in severity affecting one or more lines of hematopoiesis. Ineffective erythropoiesis results in dysregulation of iron metabolism. Most MDS patients have anemia, and some require regular red blood cell transfusions. These transfusions, in addition to factors of the disease itself, can result in iron overload (IO). Retrospective analyses suggest that MDS patients with IO have reduced overall survival and poorer outcomes following allogeneic stem cell transplant vs. those without IO. Iron chelation therapy (ICT; deferoxamine, deferasirox, or deferiprone) has been used to alleviate IO in other transfusion-dependent hematologic conditions (e.g., thalassemia), but its role in MDS has not been firmly established. A growing body of evidence suggests that ICT in MDS patients is an effective means for reducing transfusional IO and may significantly improve outcomes such as survival. The orally administered iron chelator deferasirox has been widely studied in MDS, and available studies have shown it to be generally well tolerated and effective in reducing IO in this population. The pathophysiology and clinical consequences of IO in MDS, as well as current methods for diagnosing and treating IO in these patients, are discussed.