Treatment of Iron Overload With Deferasirox (Exjade) in Hereditary Hemochromatosis and Myelodysplastic Syndrome

Summary

Hypothesis: Deferasirox can be used as a therapeutic agent to deplete the liver, heart and bone marrow of excess iron in patients with iron overload caused by myelodysplastic syndrome (MDS) and hemochromatosis (HC. Assess the effect of new serum biomarkers (NTBI and hepcidin) and MRI as indicators of iron overload and their usefulness to monitor iron depletion treatment. Study the effect of iron overload and iron depletion on intracellular signal transduction, trace metals concentrations in serum and urine and markers of oxidative stress in blood cells and urine.

Timeline

Start

2013-05

Primary completion

2017-01

Completion

2017-01

Publications

• Background Brittenham GM. Iron-chelating therapy for transfusional iron overload. N Engl J Med. 2011 Jan 13;364(2):146-56. doi: 10.1056/NEJMct1004810.
• Background Pietrangelo A. Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology. 2010 Aug;139(2):393-408, 408.e1-2. doi: 10.1053/j.gastro.2010.06.013. Epub 2010 Jun 11.
• Background Thorstensen K, Kvitland MA, Irgens WO, Hveem K, Asberg A. Screening for C282Y homozygosity in a Norwegian population (HUNT2): The sensitivity and specificity of transferrin saturation. Scand J Clin Lab Invest. 2010 Apr;70(2):92-7. doi: 10.3109/00365510903527838.
• Background Tziomalos K, Perifanis V. Liver iron content determination by magnetic resonance imaging. World J Gastroenterol. 2010 Apr 7;16(13):1587-97. doi: 10.3748/wjg.v16.i13.1587.
• Background Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079-88.
• Background Brissot P, Ropert M, Le Lan C, Loreal O. Non-transferrin bound iron: a key role in iron overload and iron toxicity. Biochim Biophys Acta. 2012 Mar;1820(3):403-10. doi: 10.1016/j.bbagen.2011.07.014. Epub 2011 Aug 9.
• Background Hori A, Mizoue T, Kasai H, Kawai K, Matsushita Y, Nanri A, Sato M, Ohta M. Body iron store as a predictor of oxidative DNA damage in healthy men and women. Cancer Sci. 2010 Feb;101(2):517-22. doi: 10.1111/j.1349-7006.2009.01394.x. Epub 2009 Oct 10.
• Background Barany E, Bergdahl IA, Bratteby LE, Lundh T, Samuelson G, Skerfving S, Oskarsson A. Iron status influences trace element levels in human blood and serum. Environ Res. 2005 Jun;98(2):215-23. doi: 10.1016/j.envres.2004.09.010.
• Background Phatak P, Brissot P, Wurster M, Adams PC, Bonkovsky HL, Gross J, Malfertheiner P, McLaren GD, Niederau C, Piperno A, Powell LW, Russo MW, Stoelzel U, Stremmel W, Griffel L, Lynch N, Zhang Y, Pietrangelo A. A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis. Hepatology. 2010 Nov;52(5):1671-779. doi: 10.1002/hep.23879.
• Background Brissot P, Ball S, Rofail D, Cannon H, Jin VW. Hereditary hemochromatosis: patient experiences of the disease and phlebotomy treatment. Transfusion. 2011 Jun;51(6):1331-8. doi: 10.1111/j.1537-2995.2010.02997.x. Epub 2010 Dec 22.
• Background Messa E, Carturan S, Maffe C, Pautasso M, Bracco E, Roetto A, Messa F, Arruga F, Defilippi I, Rosso V, Zanone C, Rotolo A, Greco E, Pellegrino RM, Alberti D, Saglio G, Cilloni D. Deferasirox is a powerful NF-kappaB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging. Haematologica. 2010 Aug;95(8):1308-16. doi: 10.3324/haematol.2009.016824. Epub 2010 Jun 9.

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Indications