No abstract

SummaryIn the last few decades, the life expectancy of regularly transfused b-thalassaemia major (TM) patients has dramatically improved following the introduction of safe transfusion practices, iron chelation therapy, aggressive treatment of infections and improved management of cardiac complications. How such changes, especially those attributed to the introduction of iron chelation therapy, improved the survival of TM patients to approach those with b-thalassaemia intermedia (TI) remains unknown. Three hundred and seventy-nine patients with TM (n = 284, dead 40) and TI (n = 95, dead 13) were followed retrospectively since birth until 30 June 2015 or death. Kaplan-Meir curves showed statistically significant differences in TM and TI survival (P < 0Á0001) before the introduction of iron chelation in 1965, which were no longer apparent after that date (P = 0Á086), reducing the Hazard Ratio of death in TM compared to TI from 6Á8 [95% confidence interval (CI) 2Á6-17Á5] before 1965 to 2Á8 (95% CI 0Á8-9Á2). These findings suggest that, in the era of iron chelation therapy and improved survival for TM, the major-intermedia dichotomy needs to be revisited alongside future directions in general management and prevention for both conditions.

This study aimed to determine the feasibility, reproducibility, and reliability of the multiecho T*2 Magnetic resonance imaging technique at 3 T for myocardial and liver iron burden quantification and the relationship between T*2 values at 3 and 1.5 T. Thirty-eight transfusion-dependent patients and 20 healthy subjects were studied. Cardiac segmental and global T*2 values were calculated after developing a correction map to compensate the artifactual T*2 variations. The hepatic T*2 value was determined over a region of interest. The intraoperator and interoperator reproducibility for T*2 measurements at 3 T was good. A linear relationship was found between patients' R?*2 (1000/T*2) values at 3 and 1.5 T. Segmental correction factors were significantly higher at 3 T. A conversion formula returning T*2 values at 1.5 T from values at 3 T was proposed. A good diagnostic reliability for T*2 assessment at 3 T was demonstrated. Lower limits of normal for 3 T T*2 values were 23.3 ms, 21.1 ms, and 11.7 ms, for the global heart, mid-ventricular septum, and liver, respectively. In conclusion, T*2 quantification of iron burden in the mid-ventricular septum, global heart, and no heavymoderate livers resulted to be feasible, reproducible, and reliable at 3 T. Segmental heart T*2 analysis at 3 T may be challenging due to significantly higher susceptibility artifacts

SummaryA multicentre randomized open-label trial was designed to assess the effectiveness of long-term sequential deferiprone-deferoxamine (DFO-DFP) 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 (8-12 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-DFO patients compared with DFP-alone patients (P = 0AE005). KaplanMeier survival analysis for the two chelation treatments did not show any statistically significant differences (long-rank test, P = 0AE3145). Adverse events and costs were comparable between the groups. The trial results show that sequential DFP-DFO treatment compared with DFP alone significantly decreased serum ferritin concentration during treatment for 5 years without significant differences regarding survival, adverse events, or costs. This trial was registered at http://www.clinicaltrials.gov as # NCT00733811.

SummaryThe relationship between diabetes mellitus (DM) and cardiac complications has never been systematically studied in thalassaemia major (TM). We evaluated a large retrospective historical cohort of TM to determine whether DM is associated with a higher risk of heart complications. We compared 86 TM patients affected by DM with 709 TM patients without DM consecutively included in the Myocardial Iron Overload in Thalassaemia database where clinical/instrumental data are recorded from birth to the first cardiovascular magnetic resonance (CMR) exam. All of the cardiac events considered were developed after the DM diagnosis. In DM patients versus non-DM patients we found a significantly higher frequency of cardiac complications (46Á5% vs. 16Á9%, P < 0Á0001), heart failure (HF) (30Á2% vs. 11Á7%, P < 0Á0001), hyperkinetic arrhythmias (18Á6% vs. 5Á5%, P < 0Á0001) and myocardial fibrosis assessed by late gadolinium enhancement (29Á9% vs. 18Á4%, P = 0Á008). TM patients with DM had a significantly higher risk of cardiac complications [odds ratio (OR) 2Á84, P < 0Á0001], HF (OR 2Á32, P = 0Á003), hyperkinetic arrhythmias (OR 2Á21, P = 0Á023) and myocardial fibrosis (OR 1Á91, P = 0Á021), also adjusting for the absence of myocardial iron overload assessed by T2* CMR and for the covariates (age and/or endocrine co-morbidity). In conclusion, DM significantly increases the risk for cardiac complications, HF, hyperkinetic arrhythmias and myocardial fibrosis in TM patients.