Deferasirox, Deferiprone and Desferrioxamine Treatment in Thalassemia Major Patients: Cardiac Iron and Function Comparison Determined by Quantitative Magnetic Resonance Imaging Early Release Paper Deferasirox, Deferiprone and Desferrioxamine Treatment in Thalassemia Major Patients: Cardiac Iron and

Background Oral deferiprone was suggested to be more effective than subcutaneous desferrioxamine for removing heart iron. Oral once-daily chelator deferasirox has recently been made commercially available but its long-term efficacy on cardiac iron and function has not yet been established. Our study aimed to compare the effectiveness of deferasirox, deferiprone and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function in thalassemia major patients by means of quantitative magnetic resonance imaging. Design and Methods From the first 550 thalassemia subjects enrolled in the Myocardial Iron Overload in Thalassemia network, we retrospectively selected thalassemia major patients who had been receiving one chelator alone for longer than one year. We identified three groups of patients: 24 treated with deferasirox, 42 treated with deferiprone and 89 treated with desferrioxamine. Myocardial iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron concentrations were measured by T2* multiecho technique. Results The global heart T2* value was significantly higher in the deferiprone (34±11ms) than in the deferasirox (21±12 ms) and the desferrioxamine groups (27±11 ms) (P=0.0001). We found higher left ventricular ejection fractions in the deferiprone and the desferrioxamine versus the deferasirox group (P=0.010). Liver iron concentration, measured as T2* signal, was significantly lower in the desferrioxamine versus the deferiprone and the deferasirox group (P=0.004). Conclusions The cohort of patients treated with oral deferiprone showed less myocardial iron burden and better global systolic ventricular function compared to the patients treated with oral deferasirox or subcutaneous desferrioxamine.

[1]  M. Cerqueira,et al.  Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. , 2002, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[2]  M. Felisi,et al.  Risk factors for death in patients with beta-thalassemia major: results of a case-control study. , 2006, Haematologica.

[3]  D. Pennell,et al.  Normalized left ventricular volumes and function in thalassemia major patients with normal myocardial iron , 2007, Journal of magnetic resonance imaging : JMRI.

[4]  S. Fisher,et al.  Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia. , 2013, The Cochrane database of systematic reviews.

[5]  A. Cnaan,et al.  Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. , 2004, Haematologica.

[6]  S. Perrotta,et al.  A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. , 2006, Blood.

[7]  Massimo Midiri,et al.  Multislice multiecho T2* cardiac magnetic resonance for the detection of heterogeneous myocardial iron distribution in thalassaemia patients , 2009, NMR in biomedicine.

[8]  V. Positano,et al.  Evaluation of the efficacy of oral deferiprone in β‐thalassemia major by multislice multiecho T2* , 2006, European journal of haematology.

[9]  A. Taher,et al.  Deferasirox (Exjade®) significantly improves cardiac T2* in heavily iron-overloaded patients with β-thalassemia major , 2008, Annals of Hematology.

[10]  P. Moraitis,et al.  The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study , 2009, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.

[11]  E. Gotsis,et al.  Cardiac magnetic resonance imaging R2* assessments and analysis of historical parameters in patients with transfusion-dependent thalassemia. , 2007, Haematologica.

[12]  D. Pennell,et al.  Myocardial iron loading in patients with thalassemia major on deferoxamine chelation. , 2006, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.

[13]  Mark A Westwood,et al.  Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. , 2006, Blood.

[14]  V. Positano,et al.  Multislice multiecho T2* cardiovascular magnetic resonance for detection of the heterogeneous distribution of myocardial iron overload , 2006, Journal of magnetic resonance imaging : JMRI.

[15]  A. Piga,et al.  Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: a retrospective analysis. , 2003, Haematologica.

[16]  Massimo Midiri,et al.  Multicenter validation of the magnetic resonance t2* technique for segmental and global quantification of myocardial iron , 2009, Journal of magnetic resonance imaging : JMRI.

[17]  M. Cerqueira,et al.  Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association , 2002, The international journal of cardiovascular imaging.

[18]  P. Alderson,et al.  Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia. , 2005, The Cochrane database of systematic reviews.

[19]  Massimo Midiri,et al.  Standardized T2* map of normal human heart in vivo to correct T2* segmental artefacts , 2007, NMR in biomedicine.

[20]  T. Coates,et al.  The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores. , 2010, Blood.

[21]  David N. Firmin,et al.  Intercentre Reproducibility of Magnetic Resonance T2* Measurements of Myocardial Iron in Thalassaemia , 2005, The International Journal of Cardiovascular Imaging.

[22]  D. Pennell,et al.  Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia. , 2010, Blood.

[23]  D. Pennell,et al.  Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia , 2002, The Lancet.

[24]  D N Firmin,et al.  Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. , 2001, European heart journal.

[25]  D. Pennell,et al.  Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia ☆ , 2003 .

[26]  A. Cnaan,et al.  Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. , 2006, Blood.

[27]  Matthew W. Darlison,et al.  Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance , 2008, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.

[28]  M. Angastiniotis,et al.  Survival of medically treated thalassemia patients in Cyprus. Trends and risk factors over the period 1980-2004. , 2006, Haematologica.

[29]  T. Coates,et al.  MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. , 2005, Blood.

[30]  Luigi Landini,et al.  Evaluation of a web-based network for reproducible T2* MRI assessment of iron overload in thalassemia , 2009, Int. J. Medical Informatics.

[31]  T. Coates,et al.  Longitudinal analysis of heart and liver iron in thalassemia major. , 2008, Blood.

[32]  P. Cianciulli,et al.  Improving survival with deferiprone treatment in patients with thalassemia major: a prospective multicenter randomised clinical trial under the auspices of the Italian Society for Thalassemia and Hemoglobinopathies. , 2009, Blood cells, molecules & diseases.

[33]  Massimo Midiri,et al.  Improved T2* assessment in liver iron overload by magnetic resonance imaging. , 2009, Magnetic resonance imaging.