Iron chelation therapy in thalassemia major: A systematic review with meta-analyses of 1520 patients included on randomized clinical trials

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 chi(2) (Q) and I-2. 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. (C) 2011 Elsevier Inc. All rights reserved.