title: When is iron overload deleterious, and when and how should iron chelation therapy be administered in myelodysplastic syndromes?
abstract: Iron overload in MDS starts even before patients become red-blood cell transfusion dependent, because disease-associated ineffective erythropoiesis suppresses hepcidin production in the liver and thus causes unrestrained iron absorption in the duodenum. However, the main cause of iron overload is regular transfusion therapy, which in MDS is associated with a risk of unclear magnitude for iron-related complications. Iron deposition in tissues can now be detected with non-invasive techniques such as T2* MRI. Iron toxicity in MDS may not only depend on the degree of tissue iron accumulation but also on the extent of chronic exposure to non-transferrin-bound iron (NTBI), including labile plasma iron (LPI) and intracellular labile iron pools, which increase the level of oxidative stress. Iron chelation therapy (ICT) can rapidly lower NTBI and LPI and more slowly mobilizes tissue iron stores. Further studies, including the ongoing TELESTO controlled trial, will more clearly define the role of ICT in MDS, including any effect on specific morbidities or mortality in the MDS setting.
authors: Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
authors: David P
authors: DP
authors: Steensma
authors: Klinik für Hämatologie, Onkologie und Klinische Immunologie, Heinrich-Heine-Universität, Moorenstr. 5, 40225 Düsseldorf, Germany. Electronic address: gattermann@med.uni-duesseldorf.de.
authors: Norbert
authors: N
authors: Gattermann
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D008279:Magnetic Resonance Imaging; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D011859:Radiography
chemical_list: D007502:Iron Chelating Agents; D007501:Iron
keywords: chelation therapy; deferasirox; deferiprone; deferoxamine; haemosiderosis; iron; myelodysplastic syndromes; red blood cell transfusion [complications]