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.
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.
Maggio
Aurelio
A
U.O.C. "Ematologia II con Talassemia", A.O. "V. Cervello", Palermo, Italy.
Vitrano
Angela
A
Capra
Marcello
M
Cuccia
Liana
L
Gagliardotto
Francesco
F
Filosa
Aldo
A
Magnano
Carmelo
C
Rizzo
Michele
M
Caruso
Vincenzo
V
Gerardi
Calogera
C
Argento
Crocetta
C
Campisi
Saveria
S
Cantella
Francesco
F
Commendatore
Francesca
F
D'Ascola
Domenico Giuseppe
DG
Fidone
Carmelo
C
Ciancio
Angela
A
Galati
Maria Concetta
MC
Giuffrida
Gaetano
G
Cingari
Rocca
R
Giugno
Giovanni
G
Lombardo
Turi
T
Prossomariti
Luciano
L
Malizia
Roberto
R
Meo
Anna
A
Roccamo
Gaetano
G
Romeo
Maria Antonietta
MA
Violi
Pietro
P
Cianciulli
Paolo
P
Rigano
Paolo
P
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
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D003676:Deferoxamine