title: Iron chelation therapy in thalassemia major: a systematic review with meta-analyses of 1520 patients included on randomized clinical trials.
abstract: The effectiveness of deferoxamine (DFO), deferiprone (DFP), or deferasirox (DFX) in thalassemia major was assessed. Outcomes were reported as means±SD, mean differences with 95% CI, or standardized mean differences. Statistical heterogeneity was tested using χ2 (Q) and I2. Sources of bias and Grading of Recommendations Assessment, Development and Evaluation system (GRADE) were considered. Overall, 1520 patients were included. Only 7.4% of trials were free of bias. Overall measurements suggest low trial quality (GRADE). The meta-analysis suggests lower final liver iron concentrations during associated versus monotherapy treatment (p<0.0001), increases in serum ferritin levels during DFX 5, 10, and 20 mg/kg versus DFO-treated groups (p<0.00001, p<0.00001, and p=0.002, respectively), but no statistically significant difference during DFX 30 mg/kg versus DFO (p=0.70), no statistically significant variations in heart T2* signal during associated or sequential versus mono-therapy treatment (p=0.46 and p=0.14, respectively), increases in urinary iron excretion during associated or sequential versus monotherapy treatment (p=0.008 and p=0.02, respectively), and improved ejection fraction during associated or sequential versus monotherapy treatment (p=0.01 and p<0.00001, respectively). These findings do not support any specific chelation treatment. The literature shows risks of bias, and additional larger and longer trials are needed.
authors.affiliation: U.O.C. Ematologia II con Talassemia, A.O. V. Cervello, Palermo, Italy. aureliomaggio@virgilio.it
authors.forename: Aurelio
authors.initials: A
authors.lastname: Maggio
authors.forename: Aldo
authors.initials: A
authors.lastname: Filosa
authors.forename: Angela
authors.initials: A
authors.lastname: Vitrano
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Aloj
authors.forename: Antonis
authors.initials: A
authors.lastname: Kattamis
authors.forename: Adriana
authors.initials: A
authors.lastname: Ceci
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.forename: Paolo
authors.initials: P
authors.lastname: Cianciulli
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grady
authors.forename: Luciano
authors.initials: L
authors.lastname: Prossomariti
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.forename: Angela
authors.initials: A
authors.lastname: Iacono
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.forename: Fedele
authors.initials: F
authors.lastname: Bonifazi
authors.forename: Filippo
authors.initials: F
authors.lastname: Cassarà
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: John
authors.initials: J
authors.lastname: Wood
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
mesh_terms: D001565:Benzoates / Q000008:administration & dosage*; D015913:Chelation Therapy / Q000706:statistics & numerical data; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005293:Ferritins / Q000097:blood; D006801:Humans; D007501:Iron; D007502:Iron Chelating Agents / Q000008:administration & dosage*; D008099:Liver / Q000378:metabolism; D016239:MEDLINE; D009206:Myocardium / Q000378:metabolism; D011728:Pyridones / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D017262:Siderophores / Q000008:administration & dosage*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*; D016276:Ventricular Function / Q000502:physiology; D017086:beta-Thalassemia / Q000097:blood / Q000188:drug therapy
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D011728:Pyridones; D017262:Siderophores; D014230:Triazoles; D000077543:Deferiprone; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox