title: Improving survival with deferiprone treatment in patients with thalassemia major: a prospective multicenter randomised clinical trial under the auspices of the Italian Society for Thalassemia and Hemoglobinopathies.
abstract: The prognosis for thalassemia major has dramatically improved in the last two decades. However, many transfusion-dependent patients continue to develop progressive accumulation of iron. This can lead to tissue damage and eventually death, particularly from cardiac disease. Previous studies that investigated iron chelation treatments, including retrospective and prospective non-randomised clinical trials, suggested that mortality, due mainly to cardiac damage, was reduced or completely absent in patients treated with deferiprone (DFP) alone or a combined deferiprone-deferoxamine (DFP-DFO) chelation treatment. However, no survival analysis has been reported for a long-term randomised control trial. Here, we performed a multicenter, long-term, randomised control trial that compared deferoxamine (DFO) versus DFP alone, sequential DFP-DFO, or combined DFP-DFO iron chelation treatments. The trial included 265 patients with thalassemia major, with 128 (48.3%) females and 137 (51.7%) males. No deaths occurred with the DFP-alone or the combined DFP-DFO treatments. One death occurred due to graft versus host disease (GVHD) in a patient that had undergone bone marrow transplantation; this patient was censored at the time of transplant. Only one death occurred with the DFP-DFO sequential treatment in a patient that had experienced an episode of heart failure one year earlier. Ten deaths occurred with the deferoxamine treatment. The main factors that correlated with an increase in the hazard ratio for death were: cirrhosis, arrhythmia, previous episode of heart failure, diabetes, hypogonadism, and hypothyroidism. In a Cox regression model, the interaction effect of sex and age was statistically significant (p-value<0.013). For each increasing year of age, the hazard ratio for males was 1.03 higher than that for females (p-value<0.013). In conclusion, the results of this study show that the risk factors for predicting mortality in patients with thalassemia major are deferoxamine-treatment, complications, and the interaction effect of sex and age.
authors.affiliation: U.O.C. "Ematologia II con Talassemia", A.O. "V. Cervello", Palermo, Italy.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Maggio
authors.forename: Angela
authors.initials: A
authors.lastname: Vitrano
authors.forename: Marcello
authors.initials: M
authors.lastname: Capra
authors.forename: Liana
authors.initials: L
authors.lastname: Cuccia
authors.forename: Francesco
authors.initials: F
authors.lastname: Gagliardotto
authors.forename: Aldo
authors.initials: A
authors.lastname: Filosa
authors.forename: Carmelo
authors.initials: C
authors.lastname: Magnano
authors.forename: Michele
authors.initials: M
authors.lastname: Rizzo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Caruso
authors.forename: Calogera
authors.initials: C
authors.lastname: Gerardi
authors.forename: Crocetta
authors.initials: C
authors.lastname: Argento
authors.forename: Saveria
authors.initials: S
authors.lastname: Campisi
authors.forename: Francesco
authors.initials: F
authors.lastname: Cantella
authors.forename: Francesca
authors.initials: F
authors.lastname: Commendatore
authors.forename: Domenico Giuseppe
authors.initials: DG
authors.lastname: D'Ascola
authors.forename: Carmelo
authors.initials: C
authors.lastname: Fidone
authors.forename: Angela
authors.initials: A
authors.lastname: Ciancio
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Galati
authors.forename: Gaetano
authors.initials: G
authors.lastname: Giuffrida
authors.forename: Rocca
authors.initials: R
authors.lastname: Cingari
authors.forename: Giovanni
authors.initials: G
authors.lastname: Giugno
authors.forename: Turi
authors.initials: T
authors.lastname: Lombardo
authors.forename: Luciano
authors.initials: L
authors.lastname: Prossomariti
authors.forename: Roberto
authors.initials: R
authors.lastname: Malizia
authors.forename: Anna
authors.initials: A
authors.lastname: Meo
authors.forename: Gaetano
authors.initials: G
authors.lastname: Roccamo
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Romeo
authors.forename: Pietro
authors.initials: P
authors.lastname: Violi
authors.forename: Paolo
authors.initials: P
authors.lastname: Cianciulli
authors.forename: Paolo
authors.initials: P
authors.lastname: Rigano
mesh_terms: D000293:Adolescent; D000328:Adult; D001803:Blood Transfusion; D002423:Cause of Death; D015913:Chelation Therapy; D002648:Child; D003131:Combined Modality Therapy; D000077543:Deferiprone; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000401:mortality; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011728:Pyridones / Q000008:administration & dosage / Q000627:therapeutic use*; D013156:Splenectomy; D015996:Survival Rate; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy
chemical_list: D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D003676:Deferoxamine