title: Efficacy and safety of deferasirox for reducing total body and cardiac iron in thalassemia.
abstract: OBJECTIVE
  To assess the efficacy of deferasirox as an iron chelator, with specific reference to reducing cardiac iron overload.
  
  
  METHODS
  Prospective, open label, single arm study between 2008-2010. SETUP: Thalassemia center at a teaching hospital.
  
  
  METHODS
  30 multitransfused Thalassemia Major (TM) patients receiving deferasirox (DFX) therapy.
  
  
  METHODS
  All patients had MRI T2*evaluation for cardiac iron load before starting DFX therapy. MRI T2* was performed on a 1.5 tesla Siemens sonata machine using thalassemia tools software and the ejection fraction measured using standard cardiac magnetic resonance sequence. Quantification of cardiac iron deposit was categorized into T2* <10 ms as high cardiac risk, 10-20 ms as intermediate risk, and >20 ms as low risk. We also estimated left ventricular ejection fraction (LVEF), end systolic volume (ESV) and end diastolic volume (EDV) using standard sequence. EF <56 % was considered to be significant cardiac dysfunction. DFX was administered in an initial dose of 20mg/kg/day and increased to a maximum of 35mg/kg/day. Serum ferritin level was estimated in pretransfusion samples at 1-3 monthly intervals. The primary end point of the study was change in serum ferritin level and cardiac MRI T2* value after 12-18 months therapy.
  
  
  RESULTS
  Of the 30 patients, cardiac iron value of >20 ms was seen in 15 (50%), whereas 9 (30%; ) had 20-10 ms, and 6 (20%) had <10 ms. The mean serum ferritin pre DFX therapy of all cases was 3859.8 ± 1690.70 ng/mL (1066 - 6725 ng/mL) and mean cardiac T2* was 23.8 ± 15.2 ms (6.24-69.2 ms). After 12 to 18 months of DFX therapy on a mean dose of 33 mg/kg/day, the mean serum ferritin was 2693.4 ± 1831.5 ng/mL (drop by 30.2%, P<0.001) and mean cardiac T2* was 24.2 ± 12.9 ms (increase of 1.6 %, P=0.87). Percentage change in cardiac iron was greater in high risk (24.8%) and intermediate risk (33.4%) patients than low risk patients (8.4%), though these values were not statistically significant. LVEF was 62.0 (± 7.0%) before treatment and changed to 58.9 (± 4.8%) after 18 months of therapy but the values remained within normal range and this change was not significant (P=0.061). Adverse effect of DFX included diarrhea, maculopapular skin rash and transient proteinuria that necessitated temporary stoppage of medication.
  
  
  CONCLUSIONS
  Deferasirox monotherapy has a good safety profile and effectively chelates total body iron. It is also a good myocardial iron chelator, more efficacious in moderate to severe cardiac iron overloaded patients.
authors: Department of Pediatrics, Dr Balabhai Nanavati Hospital, Mumbai, India. deandoc2000@hotmail.com
authors: Rashid
authors: R
authors: Merchant
authors: Javed
authors: J
authors: Ahmed
authors: Pradeep
authors: P
authors: Krishnan
authors: Bhavin
authors: B
authors: Jankharia
mesh_terms: D000293:Adolescent; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D000077588:Deferasirox; D005260:Female; D005293:Ferritins / Q000097:blood / Q000378:metabolism; D006801:Humans; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011446:Prospective Studies; D013789:Thalassemia / Q000188:drug therapy*; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D000077588:Deferasirox