Treating thalassemia major-related iron overload: the role of deferiprone

Abstract

Over the last 20 years, management for thalassemia major has improved to the point where we predict that 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 specific organ assessment of the degree of iron overload, and improvement in the treatment of hepatitis. In October 2011, the Food and Drug Administration licensed deferiprone, further increasing the available choices for iron chelation in the US. The ability to prescribe any of the three chelators as well as their combinations has led to more effective reduction of total body iron. The ability to determine the amount of iron in the liver and heart by magnetic resonance imaging allows the prescription of the most appropriate chelation regime for patients and to reconsider what our aims with respect to total body iron should be. Recent evidence from Europe has shown that by normalizing iron stores not only are new morbidities prevented but also reversal of many complications such as cardiac failure, hypothyroidism, hypogonadism, impaired glucose tolerance, and type 2 diabetes can occur, improving survival and patients' quality of life. The most effective way to achieve normal iron stores seems to be with the combination of deferoxamine and deferiprone. Furthermore, outcomes should continue to improve in the future. Starting relative intensive chelation in younger children may prevent short stature and abnormal pubertal maturation as well as other iron-related morbidities. Also, further information should become available on the use of other combinations in chelation treatment, some of which have been used only in a very limited fashion to date. All these advances in management require absolute cooperation and understanding of parents, children, and, subsequently, the patients themselves. Only with such cooperation can normal long-term survival be achieved, as adherence to treatment is now likely the primary barrier to longevity.

Keywords: deferasirox; deferiprone; deferoxamine; iron chelation therapy; iron overload; magnetic resonance imaging; thalassemia.

Figure 1

Showing the liver iron concentration (LIC) compared to cardiac T2*. The horizontal line is the level above which the heart is thought not to be excessively iron loaded. The vertical line indicates the LIC value of 7 mg/g dw.

Figure 2

Showing a forest plot indicating the odds ratio or hazard ratio for a patient to develop cardiac disease when taking deferiprone, either as monotherapy (blue circles) or in combination with deferoxamine (yellow circles), compared with taking defoxamine alone (vertical dotted line).

Figure 3

Improvement in glucose metabolism with reduction in ferritin after intensive chelation with the combination of deferoxamine and deferiprone. Notes: In 2006–2008, compliance deteriorated and with only a slight increase in ferritin and liver iron concentration, glucose metabolism deteriorated. Once compliance improved, glucose metabolism normalized. The bold line is the level below which the 2-hour glucose level is acceptable, and the broken line is the level above which it is considered that a patient is diabetic. The area between is regarded as impaired glucose tolerance. Abbreviation: OGTT, oral glucose tolerance test.