title: Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias.
abstract: OBJECTIVE
  It is widely assumed that, at matched transfusional iron-loading rates, responses to chelation therapy are similar, irrespective of the underlying condition. However, data are limited for rare transfusion-dependent anaemias, and it remains to be elucidated if response differs, depending on whether the anaemia has a primary haemolytic or production mechanism.
  
  
  METHODS
  The efficacy and safety of deferasirox (Exjade®) in rare transfusion-dependent anaemias were evaluated over 1 yr, with change in serum ferritin as the primary efficacy endpoint. Initial deferasirox doses were 10-30 mg/kg/d, depending on transfusion requirements; 34 patients had production anaemias, and 23 had haemolytic anaemias.
  
  
  RESULTS
  Patients with production anaemias or haemolytic anaemias had comparable transfusional iron-loading rates (0.31 vs. 0.30 mL red blood cells/kg/d), mean deferasirox dosing (19.3 vs. 19.0 mg/kg/d) and baseline median serum ferritin (2926 vs. 2682 ng/mL). Baseline labile plasma iron (LPI) levels correlated significantly with the transfusional iron-loading rates and with serum ferritin levels in both cohorts. Reductions in median serum ferritin levels were initially faster in the production than the haemolytic anaemias, but at 1 yr, similar significant reductions of 940 and 617 ng/mL were attained, respectively (-26.0% overall). Mean LPI decreased significantly in patients with production (P < 0.0001) and haemolytic (P = 0.037) anaemias after the first dose and was maintained at normal mean levels (< 0.4 μm) subsequently. The most common drug-related, investigator-assessed adverse events were diarrhoea (n = 16) and nausea (n = 12).
  
  
  CONCLUSIONS
  At matched transfusional iron-loading rates, the responses of rare transfusion-dependent anaemias to deferasirox are similar at 1 yr, irrespective of the underlying pathogenic mechanism.
authors.affiliation: University College London, London, UK. j.porter@ucl.ac.uk
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.forename: Kai-Hsin
authors.initials: KH
authors.lastname: Lin
authors.forename: Photis
authors.initials: P
authors.lastname: Beris
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Forni
authors.forename: Ali
authors.initials: A
authors.lastname: Taher
authors.forename: Dany
authors.initials: D
authors.lastname: Habr
authors.forename: Gabor
authors.initials: G
authors.lastname: Domokos
authors.forename: Bernard
authors.initials: B
authors.lastname: Roubert
authors.forename: Swee Lay
authors.initials: SL
authors.lastname: Thein
mesh_terms: D000293:Adolescent; D000740:Anemia / Q000188:drug therapy*; D001565:Benzoates / Q000627:therapeutic use*; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload; D008297:Male; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D007501:Iron; D000077588:Deferasirox