title: Cardiac iron load and function in transfused patients treated with deferasirox (the MILE study).
abstract: OBJECTIVE
  To assess the effect of iron chelation therapy with deferasirox on cardiac iron and function in patients with transfusion-dependent thalassemia major, sickle cell disease (SCD), and myelodysplastic syndromes (MDS).
  
  
  METHODS
  This phase IV, single-arm, open-label study over 53 wk evaluated the change in cardiac and liver iron load with deferasirox (up to 40 mg/kg/d), measured by magnetic resonance imaging (MRI).
  
  
  RESULTS
  Cardiac iron load (myocardial T2*) significantly improved (P = 0.002) overall (n = 46; n = 36 thalassemia major, n = 4 SCD, n = 6 MDS). Results were significant for patients with normal and moderate baseline cardiac iron (P = 0.017 and P = 0.015, respectively), but not in the five patients with severe cardiac iron load. Liver iron concentration (LIC) significantly decreased overall [mean LIC 10.4 to 8.2 mg Fe/g dry tissue (dw); P = 0.024], particularly in those with baseline LIC >7 mg Fe/g dw (19.9 to 15.6 mg Fe/g dw; P = 0.002). Furthermore, myocardial T2* significantly increased in patients with LIC <7 mg Fe/g dw, but not in those with a higher LIC. Safety was consistent with previous reports.
  
  
  CONCLUSIONS
  Once-daily deferasirox over 1 yr significantly increased myocardial T2* and reduced LIC. This confirms that single-agent deferasirox is effective in the management of cardiac iron, especially for patients with myocardial T2* >10 ms (Clinicaltrials.gov identifier: NCT00673608).
authors.affiliation: Institute of Haematology, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia.
authors.forename: P Joy
authors.initials: PJ
authors.lastname: Ho
authors.affiliation: Department of Haematology, Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: Lay
authors.initials: L
authors.lastname: Tay
authors.affiliation: Department of Haematology, The Children's Hospital at Westmead, Sydney, NSW, Australia.
authors.forename: Juliana
authors.initials: J
authors.lastname: Teo
authors.affiliation: Department of Haematology, Princess Alexandra Hospital, School of Medicine University of Queensland, Brisbane, QLD, Australia.
authors.forename: Paula
authors.initials: P
authors.lastname: Marlton
authors.affiliation: Department of Clinical Haematology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Grigg
authors.affiliation: University of Western Australia, Perth, WA, Australia.
authors.forename: Tim
authors.identifier: http://orcid.org/0000-0003-4682-4972
authors.initials: T
authors.lastname: St Pierre
authors.affiliation: Department of Radiology, Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Brown
authors.affiliation: Statistical Revelations Pty Ltd, Melbourne, VIC, Australia.
authors.forename: Caro-Anne
authors.initials: CA
authors.lastname: Badcock
authors.affiliation: Statistical Revelations Pty Ltd, Melbourne, VIC, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Traficante
authors.affiliation: Novartis Pharmaceuticals, Sydney, NSW, Australia.
authors.forename: Othon L
authors.initials: OL
authors.lastname: Gervasio
authors.affiliation: Thalassaemia Services Victoria, Monash Medical Centre, Melbourne, VIC, Australia.
authors.forename: Donald K
authors.initials: DK
authors.lastname: Bowden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D001803:Blood Transfusion; D015913:Chelation Therapy; D000077588:Deferasirox; D005260:Female; D005293:Ferritins / Q000097:blood; D006334:Heart Function Tests; D006453:Hemoglobinopathies / Q000150:complications / Q000628:therapy; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019190:Iron Overload / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D065227:Transfusion Reaction; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D007501:Iron; D000077588:Deferasirox
keywords: cardiac iron; deferasirox; hepatic iron; magnetic resonance imaging iron assessment; transfusional siderosis