Benefits and Risks in Polypathology and Polypharmacotherapy Challenges in the Era of the Transition of Thalassaemia from a Fatal to a Chronic or Curable Disease.

Beta thalassaemia major (TM), a potentially fatal haemoglobinopathy, has transformed from a fatal to a chronic disease in the last 30 years following the introduction of effective, personalised iron chelation protocols, in particular the use of oral deferiprone, which is most effective in the removal of excess iron from the heart. This transition in TM has been achieved by the accessibility to combination therapy with the other chelating drugs deferoxamine and deferasirox but also therapeutic advances in the treatment of related co-morbidities. The transition and design of effective personalised chelation protocols was facilitated by the development of new non-invasive diagnostic techniques for monitoring iron removal such as MRI T2*.

The History of Deferiprone (L1) and the Paradigm of the Complete Treatment of Iron Overload in Thalassaemia.

Deferiprone (L1) was originally designed, synthesised and screened in vitro and in vivo in 1981 by Kontoghiorghes G. J. following his discovery of the novel alpha-ketohydroxypyridine class of iron chelators (1978-1981), which were intended for clinical use.

Liver iron and serum ferritin levels are misleading for estimating cardiac, pancreatic, splenic and total body iron load in thalassemia patients: factors influencing the heterogenic distribution of excess storage iron in organs as identified by MRI T2*.

A comparative assessment of excess storage iron distribution in the liver, heart, spleen and pancreas of β-thalassemia major (β-ΤΜ) patients has been carried out using magnetic resonance imaging (MRI) relaxation times T2*. The β-ΤΜ patients (8-40 years, 11 males, 9 females) had variable serum ferritin levels (394-5603 μg/L) and were treated with deferoxamine (n = 10), deferiprone (n = 5) and deferoxamine/deferiprone combination (n = 5). MRI T2* assessment revealed that excess iron is not proportionally distributed among the organs but is stored at different concentrations in each organ and the distribution is different for each β-ΤΜ patient.

Efficacy, compliance and toxicity factors are affecting the rate of normalization of body iron stores in thalassemia patients using the deferiprone and deferoxamine combination therapy.

The international committee on chelation (ICOC) of deferiprone (L1) and deferoxamine (DFO) combination therapy was the first protocol reported to have achieved normal range body iron store levels (NRBISL) in β-thalassemia major (β-TM) patients. A follow-up study in eight β-TM patients has been designed to investigate the factors affecting the rate of iron removal leading to NRBISL. The patients had variable serum ferritin [mean ± SE (standard error) =1692 ± 366, range 539-3845 μg/L)] and magnetic resonance imaging (MRI) T2* relaxation times cardiac (mean ± SE =11.

Reduction of body iron stores to normal range levels in thalassaemia by using a deferiprone/deferoxamine combination and their maintenance thereafter by deferiprone monotherapy.

Background: Iron overload and toxicity is the major cause of morbidity and mortality in thalassaemia patients. New chelating drug protocols are necessary to treat completely transfusional iron overload and eliminate associated toxicity. Appropriate deferiprone/deferoxamine combinations could achieve this goal.

Risk/benefit assessment, advantages over other drugs and targeting methods in the use of deferiprone as a pharmaceutical antioxidant in iron loading and non iron loading conditions.

Tissue damage caused by oxidative stress is a common characteristic of many conditions involving different major organs such as the brain, heart, liver and kidneys. The treatment of such conditions using classical antioxidants is not in most cases sufficient or effective because it lacks specificity and has a low therapeutic index. Increased evidence from in vitro, in vivo and clinical studies suggest that deferiprone (L1) can be used as a potent pharmaceutical antioxidant by mobilizing labile iron and copper and/or inhibiting their catalytic activity in the formation of free radicals and oxidative stress in tissue damage.