Iron chelation in thalassemia: time to reconsider our comfort zones

Abstract

Over the last 20 years, the management of thalassemia major has improved to the point where we predict that the patients’ life expectancy will approach that of the normal population. These outcomes result from safer blood transfusions, the availability of three iron chelators, new imaging techniques that allow organ-specific assessment of the degree of iron overload and improvement in the treatment of hepatitis. The ability to prescribe any of the three chelators, as well as their combinations, has led to a more effective reduction of the total body iron. The ability to determine the amount of iron in the liver and heart by MRI has allowed the prescription of the most appropriate chelation regime for the patient and has allowed the reconsideration of ‘the comfort zones’. Thus, normalizing iron stores not only prevents new morbidities but also reverses many complications, such as cardiac failure, hypothyroidism, hypogonadism, impaired glucose tolerance and Type 2 diabetes, therefore improving survival and patients’ quality of life. Furthermore, outcomes should continue to improve in the future. Starting relatively intensive chelation in younger children may prevent short stature and abnormal pubertal maturation, as well as other iron-related morbidities. In addition, further information should become available on the use of other combinations in chelation treatment, some of which have only been used in a very limited fashion so far. New safe oral chelators may also become available that may offer additional ease of use. All these advances in management do require absolute cooperation and understanding on behalf of children’s parents and subsequently the adult themself. Only with such cooperation can normal long-term survival be achieved as it is likely that adherence to treatment is the primary barrier to longevity.

Keywords::

• compliance
• deferasirox
• deferiprone
• desferrioxamine
• endocrine dysfunction
• iron chelation
• magnetic resonance imaging
• thalassemia
• transfusion iron overload

Financial & competing interests disclosure

Vasili Berdoukas is a consultant for ApoPharma Inc. (Toronto, Canada) and has a confidentiality agreement with Novartis Inc. (Basel, Switzerland) with respect to the development of deferasirox. Kallistheni Farmaki was a speaker at ApoPharma key opinion leader meetings and was an investigator in Novartis Inc. studies for ICL670 (Exjade). John Wood has received funding for clinical studies from Novartis Inc. with respect to the development of deferasirox and has been a speaker for ApoPharma Inc. He is also a consultant for Ferrokin Biosciences. Thomas Coates has received funding for clinical studies from Novartis Inc. with respect to the development of deferasirox. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.