Treatment of cardiac iron overload in thalassemia major.

The inexorable tissue iron accumulation in thalas-semia major is well documented and is fatal unless chelation therapy is given to remove the iron from the tissues. Desferal thus revolutionized the treatment of iron overload in thalassemia and dramatically improved survival. Desferal has been widely available now for over two decades and initially it was thought that life expectancy might be open-ended for the majority of patients, but this has not been achieved. Recent cohorts show that only 50% of patients currently survive beyond the age of 35 years, 1 and with inadequate chelation, only 30% of patients survive over the age of 30. Some cohorts have, however, done better than this. By far the commonest cause of death is cardiac complications, accounting for well over half of all deaths. 1,3 Intensive chelation therapy with des-ferrioxamine can prevent cardiac complications, 4,5 and may reverse the deleterious effects of severe iron overload. However, there are three main, unresolved problems that have emerged with the use of desferal monother-apy. First, it must be given as intravenous or subcuta-neous infusions over prolonged periods, which are painful, cumbersome, and inconvenient and therefore compliance is compromised. An orally active chelator might offer significant advantages by improving compliance. The only current orally active chelating agent is deferiprone. Although desferal may be a more effi-cacious chelator, the issue of compliance may partly redress this balance. Second, the cost and difficulty of treatment would be significantly reduced, which is important considering the worldwide distribution of thalassemia. Third, and most importantly, there is still significant cardiac mortality with desferal, which might be lower with a different therapy. On this third issue there have been recent changes in our understanding of the distribution of iron throughout the body, and how this is affected by chelation. This is changing the understanding of iron distribution and its management. In the assessment of tissue iron loading, until recently, the main methods of assessing iron loading were serum ferritin and liver iron concentration. It is well recognized that serum ferritin is affected by a whole host of different factors, and is an unreliable marker. 7-10 Liver biopsy has until recently been regarded as the gold standard to assess total body iron, and hence the risk of not only hepatic complications but of all complications. Recent developments have cast doubt on this belief. Persistently high liver iron concentration is associated with an adverse mortality, which in …