Differential effects of the type of iron chelator on the absolute number of hematopoietic peripheral progenitors in patients with β-thalassemia major
Gian Luca Forni1⇑, Marina Podestà2, Marco Musso1, Giovanna Piaggio3, Khaled M. Musallam4, Manuela Balocco1, Sarah Pozzi3, Alessandra Rosa1 and Francesco Frassoni
1Ematologia-Centro della Microcitemia e delle Anemie Congenite, Ospedale Galliera, Genoa
2Laboratorio Cellule Staminali Post-Natali e Terapia Cellulari, Ospedale Gaslini, Genoa
3Divisione Ematologia e Trapianti di Midollo Osseo, Ospedale San Martino, Genoa
4Department of Medicine and Medical Specialties, IRCCS Ca' Granda Foundation Maggiore Policlinico Hospital, University of Milan, Milan, Italy
Correspondence: gianluca.forni@galliera.it
Abstract
Several studies have established an association between iron chelation therapy with deferasirox and hematopoietic improvement in patients with myelodysplastic syndromes. There are no data from patients with β-thalassemia major. In a cross-sectional study, we evaluated the absolute number of several hematopoietic peripheral progenitors (colony-forming unit-granulocyte/macrophage, erythroid burst-forming units, colony-forming unit-granulocyte/erythrocyte/macrophage/megakaryocyte, and long-term culture-initiating cells) in 30 patients with β-thalassemia major (median age 29.5 years, 40% males) and 12 age-matched controls. For the β-thalassemia major patients, data on splenectomy status, the type of iron chelator used, and serum ferritin levels reflecting changes in iron status on the chelator were also retrieved. All patients had to be using the same iron chelator for at least 6 months with >80% compliance. The absolute number of all hematopoietic peripheral progenitors was higher in β-thalassemia major patients than in controls, and varied between splenectomized and non-splenectomized patients (lower number of erythroid burst-forming units and higher numbers of colony-forming unit-granulocyte/macrophage, colony-forming unit-granulocyte/erythrocyte/macrophage/megakaryocyte, and long-term culture-initiating cells). The number of erythroid burst-forming units was significantly higher in patients taking deferasirox (n=10) than in those taking either deferoxamine (n=10) or deferiprone (n=10) (P<0.05). After adjusting for age, sex, splenectomy status, and serum ferritin changes, the association between a higher absolute number of erythroid burst-forming units in deferasirox-treated patients than in patients taking deferoxamine or deferiprone remained statistically significant (P=0.011). In conclusion, in β-thalassemia major patients, compared with other iron chelators, deferasirox therapy is associated with higher levels of circulating erythroid burst-forming units. This variation is independent of iron status changes and is more likely to be due to the type of chelator.
Footnotes
Authorship and Disclosures: Information on authorship, contributions, and financial & other disclosures was provided by the authors and is available with the online version of this article at
www.haematologica.org.
Received August 17, 2012.
Accepted November 21, 2012.
Copyright© 2013 Ferrata Storti Foundation