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Prepublished online as a Blood First Edition Paper on May 22, 2003; DOI 10.1182/blood-2002-10-3280.
Submitted October 31, 2002
Accepted April 7, 2003
Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone
Alan R Cohen*, Renzo Galanello, Antonio Piga, Vincenzo De Sanctis, and Fernando Tricta
Department of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
Dipartimento Scienze Biomediche e Biotecnologie, Universita di Cagliari, Cagliari, Italy
Dipartimento Scienze Pediatriche e dell'Adolescenza, Universita di Torino, Turin, Italy
Divisione di Pediatria ed Adolescentologia, Arcispedale S. Anna, Ferrara, Italy
Apotex Research Inc, Toronto, ON, Canada
* Corresponding author; email: cohen{at}email.chop.edu.
The identification of a safe, orally active iron chelator is critically important for the prevention of morbidity and early death in patients receiving regular red cell transfusions. Based on our findings in a one-year multi-center, prospective study of the safety and efficacy of deferiprone in patients with thalassemia major, we have extended the treatment period to four years. The mean dose of the chelator was 73 mg/kg/day during 531 patient-years. The rates of agranulocytosis (ANC<500 X109/L) and milder forms of neutropenia (500-1500 X 109/L) were 0.2 and 2.8 per 100 patient-years respectively. Neutropenia occurred significantly more commonly in patients with intact spleens. Gastrointestinal and joint symptoms decreased significantly after the first year of therapy, and led to discontinuation of deferiprone in only one patient in years 2-4. The mean ALT of 71 U/L after four years of therapy was significantly higher than the baseline value of 61 U/L. Trend analysis showed no increase in the ALT levels or the percentage of patients with ALT levels greater than twice the upper limit of the reference range. Ferritin levels did not change significantly from the values at the time of change from deferoxamine to deferiprone in either the intention-to-treat analysis or in the 84 patients who completed four years of therapy. Forty-seven patients discontinued therapy because of concerns regarding the effectiveness of the studied dose of deferiprone, whereas 15 patients interrupted therapy because of concerns regarding low iron levels. The results of this study help to define the safety and effectiveness of long-term therapy with deferiprone.
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