A: Deferasirox, deferiprone and desferrioxamine treatment in thalassemia major patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging. Haematologica 2011; 96

Background Oral deferiprone was suggested to be more effective than subcutaneous desferrioxamine for removing heart iron. Oral once-daily chelator deferasirox has recently been made commercially available but its long-term efficacy on cardiac iron and function has not yet been established. Our study aimed to compare the effectiveness of deferasirox, deferiprone and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function in thalassemia major patients by means of quantitative magnetic resonance imaging. Design and Methods From the first 550 thalassemia subjects enrolled in the Myocardial Iron Overload in Thalassemia network, we retrospectively selected thalassemia major patients who had been receiving one chelator alone for longer than one year. We identified three groups of patients: 24 treated with deferasirox, 42 treated with deferiprone and 89 treated with desferrioxamine. Myocardial iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron concentrations were measured by T2* multiecho technique. Results The global heart T2* value was significantly higher in the deferiprone (34±11ms) than in the deferasirox (21±12 ms) and the desferrioxamine groups (27±11 ms) (P=0.0001). We found higher left ventricular ejection fractions in the deferiprone and the desferrioxamine versus the deferasirox group (P=0.010). Liver iron concentration, measured as T2* signal, was significantly lower in the desferrioxamine versus the deferiprone and the deferasirox group (P=0.004). Conclusions The cohort of patients treated with oral deferiprone showed less myocardial iron burden and better global systolic ventricular function compared to the patients treated with oral deferasirox or subcutaneous desferrioxamine. Key words: thalassemia, iron chelation therapy, cardiac magnetic resonance imaging. Citation: Pepe A, Meloni A, Capra M, Cianciulli P, Prossomariti L, Malaventura C, Putti MC, Lippi A, Romeo MA, Bisconte MG, Filosa A, Caruso V, Quarta A, Pitrolo L, Missere M, Midiri M, Rossi G, Positano V, Lombardi M, and Maggio A. Deferasirox, deferipron

A useful relationship between the presence of extramedullary erythropoeisis and the level of the soluble form of the transferrin receptor in a large cohort of adult patients with thalassemia intermedia: A prospective study

In thalassemia intermedia (TI), the increase in bone marrow hemopoietic activity frequently leads to extramedullary erythropoeisis (EMH), but its relationship with the soluble form of transferrin receptor (sTfR) which fully reflects the marrow erythropoietic activity, has not yet been explored. From January 2007 to December 2010, all TI patients attending at our center were prospectively enrolled to undergo sTfR assay and MRI or CT (if claustrophobic) scan evaluation for the presence of paraspinal EMH. A total of 59 patients with TI were studied; EMH involved 23 (39%) patients; overall, the concentration of sTfR varied from 2.6 to 20.6 (mean=8.7) mg/L, but in splenectomized group and in unsplenectomized group, it varied from 4.2 to 17.8 (mean±SD=9. 86±3.33) mg/L and from 2.6 to 20.6 (mean±SD=7.25±3.9) mg/L, respectively with a statistically significant intergroup difference (p<0.01). The cutoff point at 8.6 mg/L using the ROC curve showed a sensitivity of 78.3% and a specificity of 72.2%, in predicting EMH but, in unsplenectomized subgroup, they raised to 100% and 90.9%, respectively. These data showed that in TI the level of sTfR could represent a predictive factor of EMH particularly in patients with spleen. © Springer-Verlag 2012

Journal of Cardiovascular Magnetic Resonance

Oral presentation Myocardial fibrosis by delayed enhancement cardiovascular magnetic resonance and HCV infection in thalassemia major patient

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&lt;0.0001), increases in serum ferritin levels during DFX 5, 10, and 20 mg/kg versus DFO-treated groups (p&lt;0.00001, p&lt;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&lt;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

Deferasirox, deferiprone and desferrioxamine treatment in thalassemia major patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging

Background Oral deferiprone was suggested to be more effective than subcutaneous desferrioxamine for removing heart iron. Oral once-daily chelator deferasirox has recently been made commercially available but its long-term efficacy on cardiac iron and function has not yet been established. Our study aimed to compare the effectiveness of deferasirox, deferiprone and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function in thalassemia major patients by means of quantitative magnetic resonance imaging. Design and Methods From the first 550 thalassemia subjects enrolled in the Myocardial Iron Overload in Thalassemia network, we retrospectively selected thalassemia major patients who had been receiving one chelator alone for longer than one year. We identified three groups of patients: 24 treated with deferasirox, 42 treated with deferiprone and 89 treated with desferrioxamine. Myocardial iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron concentrations were measured by T2* multiecho technique. Results The global heart T2* value was significantly higher in the deferiprone (34?11ms) than in the deferasirox (21?12 ms) and the desferrioxamine groups (27?11 ms) (P=0.0001). We found higher left ventricular ejection fractions in the deferiprone and the desferrioxamine versus the deferasirox group (P=0.010). Liver iron concentration, measured as T2* signal, was significantly lower in the desferrioxamine versus the deferiprone and the deferasirox group (P=0.004). Conclusions The cohort of patients treated with oral deferiprone showed less myocardial iron burden and better global systolic ventricular function compared to the patients treated with oral deferasirox or subcutaneous desferrioxamine

Long-term sequential deferiprone-deferoxamine versus deferiprone alone for thalassaemia major patients: a randomized clinical trial

A multicentre randomized open-label trial was designed to assess the effectiveness of long-term sequential deferiprone\u2013deferoxamine (DFO\u2013DFP) versus DFP alone to treat thalassaemia major (TM). DFP at 75 mg/kg, divided into three oral daily doses, for 4 d/week and DFO by subcutaneous infusion (8\u201312 h) at 50 mg/kg per day for the remaining 3 d/week was compared with DFP alone at 75 mg/kg, administered 7 d/week during a 5-year follow-up. The main outcome measures were differences between multiple observations of serum ferritin concentrations. Secondary outcomes were survival analysis, adverse events, and costs. Consecutive thalassaemia patients (275) were assessed for eligibility; 213 of these were randomized and underwent intention-to-treat analysis. The decrease of serum ferritin levels during the treatment period was statistically significant higher in sequential DFP\u2013DFO patients compared with DFP-alone patients (P = 0.005). Kaplan\u2013 Meier survival analysis for the two chelation treatments did not show any statistically significant differences (log-rank test, P = 0.3145). Adverse events and costs were comparable between the groups. The trial results show that sequential DFP\u2013DFO treatment compared with DFP alone significantly decreased serum ferritin concentration during treatment for 5 years without significant differences regarding survival, adverse events, or costs