title: Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study.
abstract: OBJECTIVE
  This 1-yr prospective phase II trial evaluated the efficacy of deferasirox in regularly transfused patients aged 3-81 yrs with myelodysplastic syndromes (MDS; n = 47), Diamond-Blackfan anaemia (DBA; n = 30), other rare anaemias (n = 22) or beta-thalassaemia (n = 85). Dosage was determined by baseline liver iron concentration (LIC).
  
  
  RESULTS
  In patients with baseline LIC > or = 7 mg Fe/g dry weight, deferasirox initiated at 20 or 30 mg/kg/d produced statistically significant decreases in LIC (P < 0.001); these decreases were greatest in MDS and least in DBA. As chelation efficiency and iron excretion did not differ significantly between disease groups, the differences in LIC changes are consistent with mean transfusional iron intake (least in MDS: 0.28 +/- 0.14 mg/kg/d; greatest in DBA: 0.4 +/- 0.11 mg/kg/d). Overall, LIC changes were dependent on dose (P < 0.001) and transfusional iron intake (P < 0.01), but not statistically different between disease groups. Changes in serum ferritin and LIC were correlated irrespective of disease group (r = 0.59), supporting the potential use of serum ferritin for monitoring deferasirox therapy. Deferasirox had a safety profile compatible with long-term use. There were no disease-specific safety/tolerability effects: the most common adverse events were gastrointestinal disturbances, skin rash and non-progressive serum creatinine increases.
  
  
  CONCLUSIONS
  Deferasirox is effective for reducing iron burden with a defined, clinically manageable safety profile in patients with various transfusion-dependent anaemias. There were no disease-specific adverse events. Once differences in transfusional iron intake are accounted for, dose-dependent changes in LIC or serum ferritin are similar in MDS and other disease groups.
authors.affiliation: University College London, London, UK. j.porter@ucl.ac.uk
authors.forename: John
authors.initials: J
authors.lastname: Porter
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Ellis J
authors.initials: EJ
authors.lastname: Neufeld
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.forename: Nancy
authors.initials: N
authors.lastname: Olivieri
authors.forename: Antonio
authors.initials: A
authors.lastname: Piga
authors.forename: Melody J
authors.initials: MJ
authors.lastname: Cunningham
authors.forename: Denis
authors.initials: D
authors.lastname: Soulières
authors.forename: Norbert
authors.initials: N
authors.lastname: Gattermann
authors.forename: Gilbert
authors.initials: G
authors.lastname: Tchernia
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.forename: Patricia
authors.initials: P
authors.lastname: Giardina
authors.forename: Janet
authors.initials: J
authors.lastname: Kwiatkowski
authors.forename: Giovanni
authors.initials: G
authors.lastname: Quarta
authors.forename: Michael
authors.initials: M
authors.lastname: Jeng
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Forni
authors.forename: Michael
authors.initials: M
authors.lastname: Stadler
authors.forename: Holger
authors.initials: H
authors.lastname: Cario
authors.forename: Louisette
authors.initials: L
authors.lastname: Debusscher
authors.forename: Matteo
authors.initials: M
authors.lastname: Della Porta
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Peter
authors.initials: P
authors.lastname: Greenberg
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
authors.forename: Bertrand
authors.initials: B
authors.lastname: Rabault
authors.forename: Insa
authors.initials: I
authors.lastname: Gathmann
authors.forename: John Malcolm
authors.initials: JM
authors.lastname: Ford
authors.forename: Daniele
authors.initials: D
authors.lastname: Alberti
authors.forename: Christian
authors.initials: C
authors.lastname: Rose
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D029503:Anemia, Diamond-Blackfan / Q000188:drug therapy*; D001565:Benzoates / Q000627:therapeutic use*; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D011446:Prospective Studies; D013789:Thalassemia / Q000188:drug therapy*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D017086:beta-Thalassemia / Q000188:drug therapy*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox