Mutagenesis vol. 18 no. 5 pp. 457-463,
September 2003
© 2003 UK Environmental Mutagen Society/Oxford University Press
Chromosomal aberration frequencies in patients with thalassaemia major undergoing therapy with deferiprone and deferoxamine in a comparative crossover study*
1Covance Laboratories Ltd, Otley Road, Harrogate, North Yorkshire HG3 1PY, UK, 2Apotex Research Inc., 150 Signet Drive, Weston, Ontario, Canada M9L 1T9 and 3Istituto di Clinica e Biologia dell’Età Evolutiva/Ospedale Regionale Microcitemie ASL, Cagliari, Italy
Measurements of chromosomal aberrations were made in 10 thalassaemia major patients treated long-term with deferiprone (at least 5 years) and compared with an equal number of patients matched for age, sex and iron overload, treated long-term with deferoxamine. Two blood samples were collected from each patient, 7 and 20 days after a transfusion episode, and the frequency of chromosomal aberrations (gaps, breaks and exchanges) in the patients’ circulating lymphocytes analysed in both samples using standard cytogenetic staining techniques. The frequency of reciprocal translocations was also analysed using fluorescence in situ hybridization. Relatively low frequencies of cells with stable and unstable aberrations were seen at both sampling times in all patients, with no statistically significant differences between sexes. Chromosomal aberrations were less frequent in patients treated long-term with deferiprone than in patients treated with deferoxamine, although the difference did not reach statistical significance. After the second blood sample had been collected, all patients had their iron chelation therapy switched to the other chelator. Patients treated long-term with deferiprone had their therapy switched to deferoxamine and patients treated long-term with deferoxamine had their therapy switched to deferiprone. After the switch, two further blood samples were collected 7 and 20 days after transfusion for each of the next two transfusion cycles in all patients. Analysis of the post-switch samples also revealed a slightly higher frequency of chromosomal aberrations during therapy with deferoxamine than with deferiprone at all time points. A small, but statistically significant, increase in cells with aberrations was observed at the first post-switch assessment in the group of patients whose therapy was switched from deferiprone to deferoxamine, whereas the switch from deferoxamine to deferiprone was associated with a decrease in the frequency of chromosomal aberrations. The results of the study demonstrate that, in a clinical setting, deferiprone has no greater clastogenic activity than that of deferoxamine.
4To whom correspondence should be addressed. Tel: +44 1423 848401; Fax: +44 1423 569595; Email: david.kirkland{at}covance.com
*The study was sponsored by Apotex. M.Spino is the Senior Vice President of Scientific Affairs and F.Tricta is the Medical Director of Apotex, the company that developed and manufactures deferiprone, the compound tested in this study
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