Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study.

Abstract

OBJECTIVES/METHODS:

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: John Porter, Renzo Galanello, Giuseppe Saglio, Ellis J Neufeld, Elliott Vichinsky, Maria Domenica Cappellini, Nancy Olivieri, Antonio Piga, Melody J Cunningham, Denis Soulières, Norbert Gattermann, Gilbert Tchernia, Johan Maertens, Patricia Giardina, Janet Kwiatkowski, Giovanni Quarta, Michael Jeng, Gian Luca Forni, Michael Stadler, Holger Cario, Louisette Debusscher, Matteo Della Porta, Mario Cazzola, Peter Greenberg, Giuliana Alimena, Bertrand Rabault, Insa Gathmann, John Malcolm Ford, Daniele Alberti, Christian Rose
• Journal: European journal of haematology (Eur J Haematol) Vol. 80 Issue 2 Pg. 168-76 (Feb 2008) ISSN: 1600-0609 [Electronic] England
• PMID: 18028431 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzoates
• Iron Chelating Agents
• Triazoles
• Deferasirox

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anemia, Diamond-Blackfan (drug therapy)
• Benzoates (therapeutic use)
• Blood Transfusion
• Child
• Child, Preschool
• Deferasirox
• Female
• Humans
• Iron Chelating Agents (therapeutic use)
• Male
• Middle Aged
• Myelodysplastic Syndromes (drug therapy)
• Prospective Studies
• Thalassemia (drug therapy)
• Treatment Outcome
• Triazoles (therapeutic use)
• beta-Thalassemia (drug therapy)