title: Differential effects of the type of iron chelator on the absolute number of hematopoietic peripheral progenitors in patients with β-thalassemia major.
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.
authors.affiliation: Ematologia-Centro della Microcitemia e delle Anemie Congenite, Ospedale Galliera, Genoa, Italy. gianluca.forni@galliera.it
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Forni
authors.forename: Marina
authors.initials: M
authors.lastname: Podestà
authors.forename: Marco
authors.initials: M
authors.lastname: Musso
authors.forename: Giovanna
authors.initials: G
authors.lastname: Piaggio
authors.forename: Khaled M
authors.initials: KM
authors.lastname: Musallam
authors.forename: Manuela
authors.initials: M
authors.lastname: Balocco
authors.forename: Sarah
authors.initials: S
authors.lastname: Pozzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rosa
authors.forename: Francesco
authors.initials: F
authors.lastname: Frassoni
mesh_terms: D000328:Adult; D001565:Benzoates / Q000627:therapeutic use; D001772:Blood Cell Count; D015913:Chelation Therapy / Q000379:methods*; D003114:Colony-Forming Units Assay; D003430:Cross-Sectional Studies; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine / Q000627:therapeutic use; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D005293:Ferritins / Q000097:blood; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000187:drug effects; D011728:Pyridones / Q000627:therapeutic use; D013156:Splenectomy; D014230:Triazoles / Q000627:therapeutic use; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood / Q000188:drug therapy*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D011728:Pyridones; D014230:Triazoles; D000077543:Deferiprone; D005293:Ferritins; D003676:Deferoxamine; D000077588:Deferasirox