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In thalassemia major, pancreatic iron was demonstrated as a powerful predictor not only for the alterations of glucose metabolism but also for cardiac iron, fibrosis, and complications, supporting a profound link between pancreatic iron and heart disease. We determined for the first time the prevalence of pancreatic iron overload (IO) in thalassemia intermedia (TI) and systematically explored the link between pancreas T2* values and glucose metabolism and cardiac outcomes. We considered 221 beta-TI patients (53.2% females, 42.95 ± 13.74 years) consecutively enrolled in the Extension–Myocardial Iron Overload in Thalassemia project. Magnetic Resonance Imaging was used to quantify IO (T2* technique) and biventricular function and to detect replacement myocardial fibrosis. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Pancreatic IO was more frequent in regularly transfused (N = 145) than in nontransfused patients (67.6% vs. 31.6%; p < 0.0001). In the regular transfused group, splenectomy and hepatitis C virus infection were both associated with high pancreatic siderosis. Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with altered OGTT. A pancreas T2* < 17.9 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for cardiac iron. Pancreas T2* values were not associated to biventricular function, replacement myocardial fibrosis, or cardiac complications. Our findings suggest that in the presence of pancreatic IO, it would be prudent to initiate or intensify iron chelation therapy to prospectively prevent both disturbances of glucose metabolism and cardiac iron accumulation.

Introduction. Pancreatic iron deposition is a common finding in thalassemia major, being detected in more than one third of patients undergoing their first T2* Magnetic Resonance Imaging scan (MRI) for this purpose. However, no longitudinal studies on pancreatic iron are available in literature. Aim: The aim of this multicenter study was to evaluate the changes in pancreatic iron overload in TM patients enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) Network who performed a baseline and a follow-up (FU) MRI scan at 18 months. Methods. We considered 416 TM patients (37.77±10.46 years; 220 females) consecutively enrolled. Iron overload was quantified by the T2* technique. T2* measurements were performed over pancreatic head, body and tail and global value was the mean. Results. Pancreatic iron overload (global pancreas T2* A significant inverse association was detected between % change in global pancreas T2*and baseline global pancreas T2* values (R=-0.369; P Changes (%) in global pancreas T2* were not associated with baseline serum ferritin levels or MRI liver iron concentration (LIC) values but were inversely correlated with % changes in serum ferritin levels (R=-0.199; P At baseline MRI, 169 patients showed an alteration of glucidic metabolism: 32 had impaired fasting glucose, 65 impaired glucose tolerance, and 72 diabetes mellitus. These patients showed significantly higher % changes in global pancreas T2* than patients with a normal glucidic metabolism (33.06±79.48% vs 11.93±59.47%; P=0.003). Conclusions. Our data showed that it is difficult to remove the iron from the pancreas and higher improvements were detected in more heavily loaded patients, with alterations of glucidic metabolism. The reduction in pancreatic iron was paralleled by a decrease in hepatic and cardiac iron. Figure 1 Figure 1. Disclosures Pepe: Bayer S.p.A.: Other: no profit support; Chiesi Farmaceutici S.p.A: Other: no profit support. Maggio: Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

To assess the transferability of the magnetic resonance imaging (MRI) multislice multiecho T2* technique for pancreatic iron overload assessment. Multiecho T2* sequences were installed on ten 1.5-T MRI scanners of the three main vendors. Five healthy subjects (n = 50) were scanned at each site. Five patients with thalassemia (n = 45) were scanned locally at each site and were rescanned at the reference site within 1 month. T2* images were analyzed using a previously validated software and the global pancreatic T2* value was calculated as the mean of T2* values over the head, body, and tail. T2* values of healthy subjects were above 26 ms and showed inter-site homogeneity. The T2* values measured in the MRI sites were comparable to the correspondent values observed in the reference site (12.02 ± 10.20 ms vs 11.98 ± 10.47 ms; p = 0.808), and the correlation coefficient was 0.978 (p

Introduction. The MIOT (Myocardial Iron Overload in Thalassemia) Network was a national Italian network constituted by thalassemia and magnetic resonance imaging (MRI) centers built in 2006. The main aim was to assure available, accessible homogeneous and standardized T2* MRI cardiac and liver iron overload assessments for a significant number of patients with emoglobinopathies. Moreover, the creation of a solid clinical-instrumental web based database allowed data exchange between centers and constituted a means of monitoring health care processes and outcomes. We describe the impact of this ten-year Network on cardiac complications in patients with thalassemia major (TM). Methods. Among the 2497 emoglobinopathies patients consecutively enrolled in the MIOT Network we considered the 1401 TM patients who performed an end-of-study MRI. Per protocol the MRI follow up was scheduled every 18±3 months. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2* technique. Biventricular function was quantified by cine images. Results. At the last MRI significantly higher global heart T2* values (35.5±10.7 ms vs 29.2±12.0 ms; P In patients with significant baseline MIO (global heart T2* Based on MRI results the 75% of the patients changed the chelation therapy. At the last MRI the percentage of patients with an excellent/good compliance was significantly higher (94.7% vs 92.7%%; P=0.034). The 13.1% of the patients had a cardiac complication (heart failure, arrhythmias, pulmonary hypertension, myocardial infarction, angina, myo/pericarditis, and peripheral vascular disease) before the enrolment in the project. During the study, the frequency of cardiac complications was 7.9 %, significantly lower (P Conclusion. Over a period of 10 years, the continuous monitoring of cardiac iron levels and a tailored chelation therapy allowed a reduction of MIO in the 70% of patients and a consequent improvement of cardiac function and reduction of heart failure. So, a national networking as the MIOT project was effective in improving the care and reducing cardiac outcomes of TM patients. Figure 1 Figure 1. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

Introduction. The aim of this multicenter study was to evaluate in thalassemia major (TM) if the cardiac efficacy of the three iron chelators in monotherapy was influenced by hepatic iron levels over a follow up of 18 months. Methods. Among the 2551 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we evaluated prospectively the 98 patients those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans and who showed evidence of significant cardiac iron (global heart T2* Results. We identified 3 groups of patients: 47 treated with deferasirox (DFX), 11 treated with deferiprone (DFP) and 40 treated with desferrioxamine (DFO). Percentage changes in cardiac R2* values correlated with changes in LIC in both DFX (R=0.469; P=0.001) and DFP (R=0.775; P=0.007) groups. All patients in these 2 groups who lowered their LIC by more than 50% improved their cardiac iron (see Figure 1). Percentage changes in cardiac R2* were linearly associated to the log of final LIC values in both DFX (R=0.437; P=0.002) and DFP groups (R=0.909; P Percentage changes in cardiac R2* were not predicted by initial cardiac R2* and LIC values. In each chelation group patients were divided in subgroups according to the severity of baseline hepatic iron overload (no, mild, moderate, and severe IO). The changes in cardiac R2* were comparable among subgroups (P=NS) (Figure 2). Conclusion. In patients treated with DFX and DFP percentage changes in cardiac R2* over 18 months were associated with final LIC and percentage LIC changes. In each chelation group percentage changes in cardiac R2* were no influenced by initial LIC or initial cardiac R2*. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc..