Iron Overload in Thalassemia and Related Conditions: Therapeutic Goals and Assessment of Response to Chelation Therapies

Transfusional iron loading inevitably results in hepatic iron accumulation, with variable extrahepatic distribution that is typically less pronounced in sickle cell disease than in thalassemia disorders Iron chelation therapy has the goal of preventing iron-mediated tissue damage through controlling tissue iron levels, without incurring chelator-mediated toxicity Historically target levels for tissue iron control have been limited by the increased frequency of deferoxamine-mediated toxicity and low levels of iron loading With newer chelation regimes these limitations are less evident The reporting of responses to chelation therapies has typically focused on average changes in serum ferritin in patient populations This approach has three limitations First changes in serum ferritin may not reflect trends in iron balance equally in all patients or for all chelation regimens Second this provides no information about the proportion of patients likely respond Third, this gives insufficient information about iron trends in tissues such as the heart Monitoring of iron overload has advanced with the increasing use of MRI techniques to estimate iron balance (changes in liver iron concentration) and extrahepatic iron distribution (myocardial T2(star)) The term nonresponder has been increasingly used to describe individuals who fail to show a downward trend in one or more of these variables Lack of a response of an individual may result from inadequate dosing high transfusion requirement poor treatment adherence or unfavorable pharmacology of the chelation regime This article scrutinizes evidence for response rates to deferoxamine deferiprone (and combinations) and deferasirox