Myocardial Iron Overload In Thalassemia Network Research Articles

National networking in rare diseases and reduction of cardiac burden in thalassemia major.

A tailored chelation therapy guided by magnetic resonance imaging (MRI) is a strategy to improve the prognosis in iron-loaded patients, in many cases still hampered by limited MRI availability. In order to address this issue, the Myocardial Iron Overload in Thalassemia (MIOT) network was established in Italy and we aimed to describe the impact of 10-year activity of this network on cardiac burden in thalassemia major (TM). Within the MIOT network, 1746 TM patients (911 females; mean age 31.2 ± 9.1 years) were consecutively enrolled and prospectively followed by 70 thalassemia and 10 MRI centres. Patients were scanned using a multiparametric approach for assessing myocardial iron overload (MIO), biventricular function, and myocardial fibrosis. At the last MRI scan, a significant increase in global heart T2* values and a significantly higher frequency of patients with no MIO (all segmental T2* ≥20 ms) were detected, with a concordant improvement in biventricular function, particularly in patients with baseline global heart T2* <20 ms. Forty-seven percentage of patients changed the chelation regimen based on MRI. The frequency of heart failure (HF) significantly decreased after baseline MRI from 3.5 to 0.8% (P < 0.0001). Forty-six patients died during the study, and HF accounted for 34.8% of deaths. Over 10 years, continuous monitoring of cardiac iron and a tailored chelation therapy allowed MIO reduction, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. A national networking for rare diseases therefore proved effective in improving the care and reducing cardiac outcomes of TM patients.

Pancreatic Iron and Bone Health in Thalassemia Major

Background. It has been shown that serum ferritin and heart iron content are good indicators of bone mineral density (BMD) in patients with beta thalassemia major (TM). In the present study we explored for the first time the relationship between pancreatic iron and BMD and bone markers in TM.Methods. We considered 135 TM patients (68 M, mean age 37.79±7.74 years) enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) Network. BMDs of the lumbar vertebrae (L1-L4) and femoral neck were measured by dual X-ray absorptiometry (DEXA) and were expressed as T-scores. Pancreatic iron overload was quantified by the T2* Magnetic Resonance Imaging (MRI) technique. Blood samples were collected for the measurement of bone formation markers (procollagen 1 amino-terminal propeptide-P1NP, osteocalcin and bone-specific-BAP alkaline phosphatise), bone resorption marker (carboxy-terminal telopeptide of type I collagen-CTX), calcium, and vitamin D.Results. Pancreatic T2* values were significantly associated to lumbar T-scores (R=0.207, P=0.017) as well as to femoral T-scores (R=0.242, P=0.005). The correlations remained significant also in patients without diabetes. Pancreatic iron (global pancreas T2*<26 ms) was detected in 8 patients. Patients with pancreatic iron showed significant lower lumbar T-scores (-2.61±0.89 vs -1.60±0.89; P=0.031) as well as femoral T-scores (-2.12±1.17 vs -1.03±0.97; P=0.009) and 7 of them (87.6%) had lumbar and femoral T-scores indicating osteopathy (osteopenia or osteoporosis).As regards as the markers, pancreatic T2* values were negatively correlated to BAP (R=-0.196 P=0.031) and positively correlated to vitamin D (R=0.220, P=0.014).Conclusion. A significant correlation, although not strong, was detected between pancreatic iron overload and bone disease. From a different point of view, our results support the role of endocrinopathies in thalassemic osteopathy and underline the critical role of a multi-disciplinary intervention in preventing bone complications. DisclosuresPepe: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.

Common Link between Bone and Heart Health in Thalassemia Major

Background. A common link between bone and heart health has been detected in the general population. In the present study we evaluated the relationship between bone mineral density (BMD) and cardiac iron, cardiovascular complications, and cardiovascular risk factors in patients with thalassemia major (TM).Methods. We considered 135 TM patients (68 M, mean age 37.79±7.74 years) enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) Network. BMDs of the lumbar vertebrae (L1-L4) and femoral neck were measured by dual X-ray absorptiometry (DEXA) and were expressed as T-scores. Myocardial iron overload (MIO) was quantified by the T2* Magnetic Resonance Imaging (MRI) technique. Blood samples were drawn for the analysis of N-terminal pro-brain natriuretic peptide (NT-proBNP), the gold standard biomarker in determining the diagnosis and prognosis of heart failure.Results. MIO (global heart t2*<20 ms) was detected in 20 (14.8%) patients. Patients with MIO showed significant lower femoral T-scores (-2.64±1.87 vs -1.96±0.99; P=0.045).Twelve patients showed cardiac complications (8 arrhythmias, 2 heart failure, 2 pulmonary hyperthension) and all of them had lumbar and femoral T-scores indicating osteopathy (osteopenia/osteoporosis). Patients with cardiac complications showed significant lower lumbar T-scores (-3.27±0.89 vs -2.43±1.29; P=0.031) and femoral T-scores (-2.96±2.02 vs -1.98±1.04; P=0.042).Patients with abnormal NTproBNP values (>157 ng/L) showed significantly lower femoral T-scores (-2.41±0.61 vs -1.79±1.16; P=0.048).Patients with diabetes (N=17) showed significant lower femoral T-scores (-2.45±0.79 vs -2.00±1.25; P=0.041).Conclusion. Lower femoral BMD was associated with MIO, cardiac complications, elevated NTproBNP values, and diabetes in patients with thalassemia major. So, our data support and interaction between bone and cardiovascular diseases in TM, suggesting that prevention and treatment strategies targeted for one of the two diseases may be beneficial for the other one. DisclosuresPepe: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.

4326Reduction of cardiac outcomes in thalassemia major thanks to a ten-year national Italian networking

Abstract Introduction The MIOT (Myocardial Iron Overload in Thalassemia) Network was a network of thalassemia and CMR centers built in 2006 in order to assure homogeneous and standardized cardiac iron overload assessment for a significant number of patients. Purpose We describe the impact of this ten-year Network on cardiac iron, complications and deaths in patients with thalassemia major (TM). Methods 1746 TM patients (911 F; age 31.17±9.09 yrs) were enrolled in the MIOT Network. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2* technique. Biventricular function was quantified by cine images. Results 1392 TM patients performed an end-of-study CMR. At the last CMR significantly higher global heart T2* values (35.44±10.69 ms vs 29.16±12.02 ms; P&lt;0.0001) and a significant lower number of patients with global heart T2*&lt;20 ms (26.3% vs 12.0%; P&lt;0.0001) were detected. Four patterns of MIO were identified: no MIO (all segments with T2*≥20 ms), heterogeneous MIO and global heart T2*≥20 ms, heterogeneous MIO and global heart T2*&lt;20 ms, and homogeneous MIO (all T2*&lt;20 ms). At the last CMR a significant higher frequency of patients with no MIO and a significant lower frequency for the other three patterns indicating MIO were found (Figure 1). In patients with global heart T2*&lt;20 ms a significant increase in left ventricular ejection fraction (EF) (difference: 3.2±8.5%, P&lt;0.0001) as well as in right ventricular EF (difference: 1.2±8.9%, P=0.002) were detected. Based on CMR results the 75% of the patients changed the chelation therapy. At the last CMR the percentage of patients with an excellent/good compliance was significantly higher (94.8% vs 92.2%%; P&lt;0.0001). The complete history of cardiac complications-CC (heart failure, arrhythmias, pulmonary hypertension, myocardial infarction, angina, myo/pericarditis, peripheral vascular disease) was present for 1062 patients. Out of the 1001 patients with resolved CC or without CC before the enrolment in the project, the 6.6% had a CC before the enrolment in the project. During the study, the frequency of CC was 4.4%, significantly lower (P=0.023). In particular, the frequency of heart failure (HF) was significantly lower (3.5% vs 0.8%, P&lt;0.0001). Forty-six patients died during the study. HF continues to be the leading cause of death (30.4% of all causes), but there was a consistent decline in HF mortality rate, that was 60.2% in an Italian study dated 2004. No patients died for arrhythmias while cancer was the second leading cause of death. 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, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. So, a national networking was effective in improving the care and reducing cardiac outcomes of TM patients.

PF786 REDUCTION OF CARDIAC OUTCOMES IN THALASSEMIA MAJOR THANKS TO A TEN‐YEAR NATIONAL ITALIAN NETWORKING

Background:The MIOT (Myocardial Iron Overload in Thalassemia) Network was a network of thalassemia and CMR centers built in 2006 in order to assure homogeneous and standardized cardiac iron overload assessment for a significant number of patients.Aims:We describe the impact of this ten‐year Network on cardiac iron, complications and deaths in patients with thalassemia major (TM).Methods:1746 TM patients (911 females; mean age 31.17 ± 9.09 yrs) were enrolled in the MIOT Network. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2∗ technique. Biventricular function was quantified by cine images.Results:1392 TM patients performed an end‐of‐study CMR. At the last CMR significantly higher global heart T2∗ values (35.44 ± 10.69 ms vs 29.16 ± 12.02 ms; P &lt; 0.0001) and a significant lower number of patients with global heart T2∗&lt;20 ms (26.3% vs 12.0%; P &lt; 0.0001) were detected. Four patterns of MIO were identified: no MIO (all segments with T2∗≥20 ms), heterogeneous MIO and global heart T2∗≥20 ms, heterogeneous MIO and global heart T2∗&lt;20 ms, and homogeneous MIO (all T2∗&lt;20 ms). Figure 1 shows the frequency of the 4 patterns at both scans. At the last CMR a significant higher frequency of patients with no MIO and a significant lower frequency for the other three patterns indicating MIO were detected.In patients with global heart T2∗&lt;20 ms a significant increase in left ventricular ejection fraction (EF) (difference: 3.2 ± 8.5 %, P &lt; 0.0001) as well as in right ventricular EF (difference: 1.2 ± 8.9 %, P = 0.002) were detected.Based on CMR results the 75% of the patients changed the chelation therapy. At the last CMR the percentage of patients with an excellent/good compliance was significantly higher (94.8% vs 92.2%%; P &lt; 0.0001).The complete history of cardiac complications‐CC (heart failure, arrhythmias, pulmonary hypertension, myocardial infarction, angina, myo/pericarditis, peripheral vascular disease) was present for 1062 patients. Out of the 1001 patients with resolved CC or without CC before the enrolment in the project, the 6.6% had a CC before the enrolment in the project. During the study, the frequency of CC was 4.4 %, significantly lower (P = 0.023). In particular, the frequency of heart failure (HF) was significantly lower (3.5% vs 0.8%, P &lt; 0.0001).Forty‐six patients died during the study. HF continues to be the leading cause of death (30.4% of all causes), but there was a consistent decline in HF mortality rate, that was 60.2% in an Italian study dated 2004. No patients died for arrhythmias while cancer was the second leading cause of death.Summary/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, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO‐related HF. So, a national networking was effective in improving the care and reducing cardiac outcomes of TM patients.image

PS1295 IRON IN THE HUMAN HEARTS: DISTRIBUTION AND ASSOCIATION WITH R2∗ VALUES BY CMR

Background:T2∗ (or R2∗ = 1000/T2∗) cardiac magnetic resonance (CMR) allows the non‐invasive and reproducible measurement of myocardial iron and has been established as fundamental to the best practice management of iron loaded patients to improve morbidity and mortality.Aims:In the present study we calibrated cardiac R2∗ values against myocardial tissue ‐measured iron concentration by using a segmental approach and we assessed the distribution and regional variations in iron distribution.Methods:Five hearts of patients with thalassemia were donated after death (N = 4) or cardiac transplantation (N = 1) to the CoreLab of the MIOT (Myocardial Iron Overload in Thalassemia) Network. A multislice multiecho T2∗ approach was adopted. After CMR, used as guidance, the heart was cut in three short‐axis slice and each slice was cut into different equiangular segments accordingly with AHA segmentation and differentiated into endocardial and epicardial layer, the same ones in which the T2∗ was assessed. Tissue iron concentration in the segments was measured with an atomic absorption spectrometer.Results:55 samples were used since it was possible to analyze all the 16 samples only from two hearts due to medical‐forensic reasons. The mean iron concentration in all samples was 4.71 ± 4.67 mg/g dw. Segmental iron levels ranged from 0.24 to 13.78 mg/g dw. Mean iron concentration was significantly higher in the epicardial than in the endocardial layer (5.99 ± 6.01 mg/g dw vs 4.84 ± 4.87 mg/g dw; P = 0.042).The coefficient of variability (CoV) of iron for myocardial segments ranged from 8.08% to 24.54%, with a mean value for all patients of 13.49 ± 6.93%. Four different main circumferential regions (anterior, septal, inferior and lateral) were defined. A circumferential heterogeneity was noted, with more iron observed in the anterior region, followed by the inferior region. The heterogeneity in circumferential iron concentration expressed as percentage deviation of the regions from the global value is shown in the Figure 1A.A strong linear correlation (R‐square = 0.956) was found by plotting ln(R2∗‐ROI) and ln[Fe] with a slope s = 0.654 (95% confidence intervals‐CI = 0.616–0.693) and intercept i = 4.216 (95% CI = 4.150–4.281) (Figure 1B). The linear relation was converted to the calibration curve: [Fe] = 0.001591 X (R2∗)1.529.Summary/Conclusion:Our data suggests an heterogeneous pattern of cardiac iron distribution with higher epicardial layer involvement. Heart R2∗ provided a robust calibration against chemically assayed cardiac iron, further validating the current clinical practice of monitoring cardiac iron in vivo by CMR.image

Impact of a Ten-Year National Italian Networking on Cardiac Complications in Patients with Thalassemia Major

▪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<0.0001) and a significant lower number of patients with global heart T2*<20 ms (26.3% vs 12.0%; P<0.0001) were detected. Four patterns of MIO were identified: no MIO (all segments with T2*≥20 ms), heterogeneous MIO and global heart T2*≥20 ms, heterogeneous MIO and global heart T2*<20 ms, and homogeneous MIO (all segments with T2*<20 ms). Figure 1 shows the frequency of the 4 patterns at both scans. At the last MRI a significant higher frequency of patients with no MIO and a significant lower frequency for the other three patterns indicating MIO were detected. An improvement in MIO, that is a transition to a better risk class, was detected in the 68.4% of patients showing MIO at the baseline (at least one pathologic segment).In patients with significant baseline MIO (global heart T2*<20 ms) a significant increase in left ventricular ejection fraction (EF) (mean difference: 3.2±8.5 %, P<0.0001) as well as in right ventricular EF (mean difference: 1.2±8.9 %, P=0.002) were detected with a concordant improvement of MIO status.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<0.0001). In particular, the frequency of heart failure was significantly lower (5.9% vs 1.7%, P<0.0001).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. [Display omitted] DisclosuresPepe:Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

A MRI Prospective Survey on Heart and Liver Iron and Cardiac Function in Thalassemia Major Patients Treated with Deferasirox Versus Deferiprone and Desferrioxamine in Monotherapy

Background: No prospective data are available about the efficacy of deferasirox versus deferiprone and desferrioxamine in monotherapy. Our study aimed to prospectively assess the efficacy of deferasirox versus deferiprone and desferrioxamine in monotherapy in a large cohort of thalassemia major (TM) patients by quantitative Magnetic Resonance (MR).Methods: Among the 2551 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we selected those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans. We identified three groups of patients: 235 treated with DFX, 142 with DFP and 162 with DFO. Iron overload was measured by T2* multiecho technique. Liver T2* values were converted into liver iron concentration (LIC) values. Biventricular function parameters were quantitatively evaluated by cine images.Results: Excellent/good levels of compliance were similar in the DFX (98.7%) vs DFP (96.3%) and DFO (97.5%) groups.Among the patients with myocardial iron overload at baseline, in all three groups there was a significant improvement in the global heart T2* value (DFX: +4.58±5.91ms P<0.0001, DFP: 8.53±6.97ms P<0.0001 and DFO: +3.93±5.21 ms P<0.0001) and a reduction in the number of pathological segments (DFX: -4.49±4.55 P<0.0001, DFP: -8.08±5.5.84 ms P=0.001 and DFO: -3.65±3.81 ms P<0.0001). In DFP and in DFO groups there was a significant improvement in left ventricular ejection function (LVEF) (+4.86±6.99% P=0.044 and +3.87±7.48% P=0.004, respectively). Only in the DFP group there was a significant improvement in right ventricular ejection function (RVEF) (6.69±4.61% P=0.001). The improvement in the global heart T2* was significantly lower in the DFX versus the DFP group , but it was not significantly different in the DFX versus the DFO group (Figure 1). The improvement in the LVEF was significantly higher in both DFP and DFO groups than in the DFX group while the improvement in the RVEF was significantly higher in the DFP than in DFX group (Figure 2).Among the patients with hepatic iron at baseline (LIC≥3mg/g dw) the changes were not significantly different in DFX versus the other groups.Conclusions: Prospectively in a large clinical setting of TM patients, DFX monotherapy was significantly less effective than DFP in improving myocardial siderosis and biventricular function and it was significantly less effective than DFO in improving the LVEF. [Display omitted] [Display omitted] DisclosuresPepe: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..

Association Between Cardiac Iron Clereance and Hepatic Siderosis

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*<20 ms) at the basal MRI. Iron overload (IO) was measured by T2* multiecho technique. We used cardiac R2* (equal to 1000/T2*) because cardiac R2* is linearly proportional to cardiac iron and hepatic T2* values were converted into liver iron concentration (LIC) values.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<0.0001).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*. [Display omitted] [Display omitted] DisclosuresPepe: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..

Deferiprone Has a Dose-Dependent Effect on Liver Iron Concentration

▪Purpose: The aim of this multi-centre study was to retrospectively assess in thalassemia major (TM) if deferiprone (DFP) had a dose-dependent effect on liver iron concentration (LIC) assessed by quantitative magnetic resonance imaging (MRI).Methods: Among the 958 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we identified hose with an MRI follow up study at 18±3 months who had been received DFP monotherapy and had no changes in dose of DFP between the 2 MRI scans. Patients were divided into two groups according to the DFP dose: 79 patients with ≤ 75 mg/kg/d (group 1) and 39 with > 75 mg/kg/d (group 2).Hepatic iron overload was measured by the T2* multiecho technique and T2* values were converted into LIC values using the calibration curve introduced by Wood et al.Results: The two groups had comparable baseline MRI LIC values. The table shows the evolution of different iron overload risk classes between the baseline and the FU MRI. The percentage of patients that worsened their status was significantly higher in group 1 than in group 2 (26.6% vs 7.7%; P=0.016).Subgroup analysis in patients with hepatic iron overload at baseline (MRI LIC > 3mg/g/dw) was conducted: 48 patients from group 1 (DFP dose: mean 70.6±11.2 mg/kg/d, median 75 mg/kg/d) and 30 from group 2 (DFP dose: mean 85.2±6.6 mg/kg/d, median 84 mg/kg/d). The two subgroups had comparable baseline MRI LIC values (10.2±8.1 mg/g dw vs 11.1±8.7 mg/g dw (P=0.314). While the mean change in subgroup 2 ( -1.8±6.3mg/g/dw, P=0.131) was more favourable than in subgroup 1 (+0.1±7.7 mg/g/dw, P=0.903), the change in MRI LIC values did not reach statistical significance between the two subgroups (P=0.579) (Figure 1), which may be due to small cohort evaluated.Conclusions: In TM patients the worsening in MRI LIC can be prevented by increasing the dose of deferiprone above the widely used regimen of 75 mg/kg body weight. Our results are consistent with the iron balance studies performed by Grady RW et al.Table 1Evolution of different iron overload risk classes between the baseline and the FU MRI. The underlined numbers represent the patients who remained in the same risk class.DFP dose ≤ 75 mg/kg/d (N=79)FU LIC<3 mg/g dw3-7 mg/g dw7-15 mg/g dw≥15 mg/g dwBaseline LIC<3 mg/g dw (N=31)217303-7 mg/g dw (N=22)104627-15 mg/g dw (N=14)0653≥15 mg/g dw (N=12)1056Total at the FU32171911DFP dose > 75 mg/kg/d (N=39)FU LIC<3 mg/g dw3-7 mg/g dw7-15 mg/g dw≥15 mg/g dwBaseline LIC<3 mg/g dw (N=9)62103-7 mg/g dw (N=14)311007-15 mg/g dw (N=8)0440≥15 mg/g dw (N=8)1025Total at the FU101775 [Display omitted] DisclosuresPepe:Chiesi: Speakers Bureau; ApoPharma Inc: Speakers Bureau; Novartis: Speakers Bureau.

Prospective changes of cardiac iron and function by MR in pediatric thalassemia major patients treated with different chelators or not chelated

Background There are no prospective studies comparing the effectiveness of the three iron chelators commercially available in preventing or decreasing iron overload in the heart in pediatric thalassemia major (TM) patients. Our aim was to evaluate the changes in cardiac iron and function by quantitative magnetic resonance imaging (MRI) over a follow-up (FU) of 18 months in pediatric TM patients treated with one of the 3 available iron chelators in monotherapy or non-chelated. Methods Among the first 1611 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we considered pediatric patients who had maintained the same chelation regimen between the two MRI scans. Myocardial iron overload (MIO) was quantified by a multislice multiecho T2* sequence. Biventricular function parameters were evaluated by cine images. Due to the low sample size, no inter-treatment comparisons were performed.

Prospective Changes of Cardiac and Hepatic Iron and Cardiac Function By MR in Pediatric Thalassemia Major Patients Treated with Different Chelators or Not Chelated

Background: There are no prospective studies comparing the effectiveness of the three iron chelators commercially available in preventing or decreasing iron overload in the heart and liver in pediatric thalassemia major (TM) patients. Our aim was to evaluate the changes in cardiac and hepatic iron and in cardiac function by quantitative magnetic resonance imaging (MRI) over a follow-up (FU) of 18 months in pediatric TM patients treated with one of the 3 available iron chelators in monotherapy or non chelated.Methods: Among the first 1611 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we considered pediatric patients who had maintained the same chelation regimen between the two MRI scans. Iron overload was quantified by multiecho T2* sequence. Hepatic T2* values were converted into liver iron concentration (LIC) values. Biventricular function parameters were evaluated by cine images. Due to the low sample size, no inter-treatment comparisons were performed and intra-treatment comparison was performed only in the DFX group.Results: Four groups of patients were identified: 6 patients (3 F, 10.0±2.2 years) treated with desferioxamine (DFO– mean dosage 43.7±6.8 mg/kg/die), 7 patients (3 F, 15.5±1.7 yrs) treated with deferiprone (DFP– mean dosage 75.0±9.2 mg/kg/die), 39 patients (13 F, 13.58±3.39 yrs) treated with deferasirox (DFX– mean dosage 26.6±6.7 mg/kg/die), and 2 patients (2 F, 11.1±5.3 yrs) not chelated because they had performed a bone marrow transplantation. Compliance to chelation therapy was excellent/good in all treated groups.At baseline in DFO, DFP and no chelated groups no patient showed a global heart T2* value<20 ms. In all 4 groups all patients who showed no cardiac iron overload at baseline maintained at the FU the same status. At baseline in DFX group 6 patients (17.6%) had heart T2* values<20 ms. The 4 patients with intermediate cardiac iron (T2* 10-20 ms) at the baseline showed no iron at the FU while the patient with severe cardiac iron (T2*<10 ms) remained in the same status at the FU. Non chelated patients had higher global heart T2* values at baseline (non-chelated 37.7±0.5 ms > DFP 35.3±4.9 ms > DFX 32.7±9.6 ms > DFO 31.9±10.5 ms) while DFP patients had higher global heart T2* values at FU (DFP 39.5±6.1 ms > DFX 34.2±7.3 ms > DFO 33.6±7.9 ms > non-chelated 28.9±4.0 ms ).In the DFO group at baseline 1 patient showed pathological left ventricular ejection fraction (LVEF) and he recovered at the follow up. In the DFP group at baseline 2 patients showed pathological LVEF and both recovered at the follow up. In the DFX group at baseline 3 patients showed pathological LVEF: 2 recovered at the FU and 1 did not perform the evaluation of the cardiac function at FU due to technical reasons. Conversely 9 patients with normal LVEF at baseline showed pathological LVEF at the FU.In the DFO group the percentage of patients with MRI LIC>3 mg/g/dw went up from 83% to 100%. In the DFP group all patients showed MRI LIC>3 mg/g/dw at baseline and they maintained this status at the FU. In the DFX group the percentage of patients with MRI LIC≥3 mg/g/dw went down from 71.1% to 52.6%. The MRI LIC mean difference was -1.6±4.4 mg/g/dw (P=0.006). Only one of the two non chelated patients had a baseline MRI LIC≥3 mg/g/dw and she remained in the same status at the FU.Conclusion: This longitudinal analysis confirms significant rate of iron overload even in very young TM population, in particular in the liver. In this population, DFP seems to be more effective in the heart with a concordant positive effect on the global systolic function. Conversely, DFX seems to be more effective in the liver. However, further prospective studies are needed on larger study population to confirm the data. [Display omitted] DisclosuresPepe:Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.

MRI Prospective Survey on Cardiac and Hepatic Iron in Thalassemia Intermedia Patients Treated with Desferrioxamine, Deferiprone and Deferasirox

Background. Few studies have evaluated the efficacy of iron chelation therapy in thalassemia intermedia (TI) patients. Our study aimed to prospectively assess by quantitative Magnetic Resonance imaging (MRI) the efficacy of the three available chelators in monotherapy in transfusion dependent (TD) TI patients.Methods. Among the 325 TI patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we selected 103 TI patients TD with an MRI follow-up (FU) study at 18±3 months who had been received one chelator alone between the two MRI scans. Iron overload was assessed by the T2* multiecho technique. Hepatic T2* values were converted into liver iron concentration (LIC) values.Results. Three groups of patients were identified: 27 patients (13 females, mean age 40.12±10.31 years) treated with desferioxamine (DFO – mean dosage 37.52±8.69 mg/kg/die), 23 patients (14 females, mean age 34.73±10.67 years) treated with deferiprone (DFP– dosage 71.70±14.46mg/kg/die) and 14 patients (9 females, mean age 36.63±10.92 years) treated with deferasirox (DFX – mean dosage 27.75±5.04 mg/kg/die). Excellent/good levels of compliance were similar in the DFO (92.6%), DFP (100%) and DFX (100%) groups (P=0.345). The mean starting age of regular transfusion was 14.73±15.89 years.At baseline in DFO group two patients (7.4%) showed a global heart T2*<20 ms and one of them showed no cardiac iron at the FU. At baseline in DFP group two patients (8.7%) showed a global heart T2*<20 ms and one of them showed no cardiac iron at the FU. All the 5 patients (35.7%) under DFX therapy with pathological global heart T2* at the baseline remained at the same status at the FU. The percentage of patients who maintained a normal global heart T2* value was comparable for DFO (100%), DFP (100%) and DFX (88.9%) groups (P=0.164).Among the 46 patients with hepatic iron at baseline (MRI LIC ≥3 mg/g/dw), the reduction in the MRI LIC values was significant only in the DFO group (DFO: -3.39±6.38 mg/g/dw P=0.041; DFP: -2.25±6.01 mg/g/dw P=0.136 and DFX: -0.36±5.56 mg/g/dw P=0.875). The decrease in MRI LIC values was comparable among the groups (P=0.336). The number of patients with a MRI LIC<3 mg/g/dw went up from 10 (37%) to 11 (40.7%) in the DFO group, from 6 (26.1%) to 8 (34.8%) in the DFP group and from 2 (14.3%) to 8 (57.1%) in the DFX group. The percentage of patients who maintained a normal MRI LIC value was comparable for DFO (90%) vs DFP (50%) and DFX (100%) groups (P=0.191).Conclusion: Prospectively in transfusion-dependent TI patients at the dosages used in the clinical practice, DFO and DFP showed 100% efficacy in maintaining a normal global heart T2* value while DFX had 100% efficacy in maintaining a normal LIC value. Further prospective studies involving more patients with iron at the baseline are needed to establish which is the most effective drug in reducing iron levels. [Display omitted] [Display omitted] DisclosuresPepe:Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.

A T2* MRI Prospective Survey on Cardiac and Hepatic Iron in Non-Trasfusion-Dependent Thalassemia Intermedia Patients Treated with Desferrioxamine

Background. In thalassemia intermedia (TI) patients no observational study prospectively evaluated in the real life the efficacy of the desferrioxamine (DFO) therapy in removing or preventing iron overload from the heart and the liver by T2* Magnetic Resonance Imaging (MRI). The efficacy endpoint of this study is represented by the changes in cardiac T2* and MRI LIC (liver iron concentration) values in non-transfusion dependent (NTD) TI patients after 18 months of desferrioxamine therapy.Methods. Among the 325 TI patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we selected 129 TI patients NTD. We considered 29 patients who had been received DFO alone between the two MRI scans. Cardiac iron overload was assessed by the T2* multiecho technique. Hepatic T2* values were converted into liver iron concentration (LIC) values.Results. Mean age was 39.69 ± 8.12 years and 14 (48.3%) patients were females. Patients started regular chelation therapy at a mean age of 21.92 ± 15.89 years. The mean administered dosage of DFO via subcutaneous route was 38.46 ± 10.27 mg/kg body weight on 3.32 ± 1.54 days/week. The percentage of patients with excellent/good levels of compliance to the chelation treatment was 82.1%.At baseline only one patient showed cardiac iron overload (global heart T2*=15.23 ms) but he recovered at the FU (global heart T2*=26.93 ms). All patients without cardiac iron maintained the same status at the follow-up (FU).Eighteen patients (62.1%) had hepatic iron overload (MRI LIC ≥3 mg/g/dw) at the baseline.For this subgroup, the baseline and the FU LIC values were, respectively, 9.15 ± 7.97 mg/g/dw and 7.41 ± 6.28 mg/g/dw. The reduction in MRI LIC values was not significant (P=0.102). Out of the 11 patients with a baseline MRI LIC <3 mg/g/dw, only one (9.1%) showed hepatic iron at the FU. The Figure shows the evolution of different hepatic iron overload risk classes between the baseline and the FU.Conclusions. In this small population of sporadically or non transfused TI patients, DFO showed 100% efficacy in maintaining a normal global heart T2* value. As regards as the hepatic iron overload, the DFO therapy did not prevent the transition to a worst class in 2 patients. [Display omitted] DisclosuresPepe:Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.

Direct Cost Analysis About The Three Chelators For The Treatment Of Thalassemia Patients With Chronic Iron Overload: An Italian Perspective From The MIOT Network

IntroductionIn thalassemia major (TM) three iron chelators in monotherapy are available to treat chronic iron overload due to blood transfusions: subcutaneous desferrioxamine (DFO) introduced in the 1960s, oral deferiprone introduced in 1999 and oral deferasirox (DFX) licensed in 2006. Nowadays pharmacoeconomics analysis are frequently required by the health authorities due to the actual economic crisis. The aim should be to ensure to the whole community the sustainability for health care of proved quality. The objective of this study was to determine the costs of the three chelators in monotherapy in a cohort of 193 TM patients followed prospectively for 18 ± 3 months. MethodsWithin the MIOT (Myocardial Iron Overload in Thalassemia) network, we evaluated prospectively 193 TM patients who had been received one chelator alone between the 2 Magnetic Resonance scans and we calculated the direct costs (drug, administration and monitoring) for each patient treated with DFX, DFO and DFP. We used the cost values for the year 2007. For the drugs we considered the cost ex-factory. For the oral chelators the administration cost was considered null. For the DFO we calculated the costs for the administration (pump, infusion set, syringes and gauzes) using the tariffs applied in Veneto Region, Italy. For the monitoring costs we considered the exams suggested in the technical sheet for each drug; we considered the tariffs by the Veneto Region, Italy. In Italy Veneto Region was proved to be one of the most upright region in the health costs management. In the analysis we considered the drug cost for the standard dosage reported in the technical sheet: 40 mg/kg/d for DFO, 75 mg/kg/d for DFP and 30 mg/kg/d for DFX. Based on the mean weight of the patients we referred the drug cost to a patient of 60 Kg. ResultsIn the clinical practice the dose of DFX was 26±7 mg/kg/d, DFP was 73±13 mg/kg/d and DFO was 41±6 mg/kg for 5.5 d/wk. Excellent/good levels of compliance were similar in the 3 groups (DFX 99%, DFP 95%; DFO 96%, P=0.6). The cost/mg was € 0.006 for Generic DFO, € 0.003 for Ferriprox® (DFP) and € 0.047 for Exjade® (DFX). For 18 months of treatment the total costs for DFO were € 10.465,8 (administration and monitoring costs € 3.965,1 + drug cost 6.500,7), for DFP were € 8.292,9 (administration and monitoring costs € 460,8 + drug cost 7.832,2), for DFX were € 46.461,2 (administration and monitoring costs € 211,14 + drug cost 46.249,8). The details about the administration and monitoring costs for DFO, DFP and DFX are reported in the table.Unit Cost (€)Number/yearCost/18 months (€)DFOPump12410.25465.375Thalaset4.23902457Syringes1.24390725.4Gauze0.0736538.325Audiometry18.65139.5Ophthalmology18.65139.5DFPNeutrophil count4.3552339.3Serum creatinine1.61227.9AST and ALT5.21293.6DFXAudiometry18.6127.9Ophthalmology18.6127.9Serum Creatinine1.551739.5Proteinuria1.31222.5AST and ALT5.21293.6 ConclusionIn this analysis, for managing chronic iron overload the direct costs for oral DFP appeared to be the less expensive. The limit of this study is that a cost-utility analysis taking into account efficacy, adverse events and route of administration was not performed. Disclosures:Pepe:ApoPharma inc, Novartis, Chiesi: Speakers Bureau.

Myocardial Iron overload In Thalassemia Major. how Early To Check?

Introduction It is still controversy in thalassemia major (TM) if Cardiovascular Magnetic Resonance (CMR) T2* screening should be initiated before the 10 years. To answer this question, we studied retrospectively the prevalence of cardiac iron and function and myocardial fibrosis by CMR in a consistent cohort of TM patients younger than 10 years. Methods From the 2171 patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we retrospectively selected the 35 TM patients aged less than 10 years who had undergone at least one MRI scan. Myocardial iron overload (MIO) was measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated in a standard way by cine images. To detect myocardial fibrosis, late gadolinium enhancement images were acquired. Results Patients’ age ranged from 4.2 to 9.7 years. All MRI scans were performed without sedation. Nine patients (25.7%) showed no myocardial iron overload (MIO),22 patients (62.9%) showed an heterogeneous MIO with a T2* global value ≥ 20 ms; 2 patients (5.7%) showed an heterogeneous MIO and a T2* global value &lt; 20 ms and 2 patients (5.7%) had a homogeneous MIO. No patients showed myocardial fibrosis. Table 1 reports the data of the 4 patients (3 males and 1 female) with significant myocardial iron overload (global heart T2* &lt; 20 ms). The youngest was 6 years old, all showed no heart dysfunction and in all the iron transfused was less than 35 g. Conclusion The first cardiac T2* assessment should be performed as early as possible without sedation and it is mandatory whenever poor compliance is suspected or if chelation has been started late. The use of the contrast medium to detect myocardial fibrosis can be postponed until after 10 years of age. A more sensitive segmental approach to detected heart iron should be considered. Therapy can be modified on the basis of the MRI results and serious organ damage can be prevented. Disclosures: No relevant conflicts of interest to declare.

Regional Myocardial Contractility In Thalassemia Major By Magnetic Resonance Tagging

Introduction Magnetic resonance (MR) tagging analyzed by dedicated tracking algorithms allows very precise measurements of myocardial motion and characterization of regional myocardial function. No extensive data are available in literature. Our aim was to quantitatively assess for the regional myocardial contractility in thalassemia major (TM) patients and to correlate it with heart iron overload and global biventricular function. Methods Seventy-four TM patients (46 F; 31.8 ± 8.5 yrs) enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network underwent MR (1.5T). Three short-axis (basal, medial and apical) tagged MR images were analyzed off-line using harmonic phase (HARP) methods (Diagnosoft software) and the circumferential shortening (Ecc) was evaluated for all the 16 myocardial segments. Four main circumferential regions (anterior, septal, inferior, and lateral) were defined. The same axes were acquired by a T2* GRE multiecho technique to assess myocardial iron overload (MIO). Biventricular function parameters were quantitatively evaluated by cine images. Results Segmental ECC values ranged from -9.66 ± 4.17 % (basal anteroseptal segment) to 13.36 ± 4.57 % (mid-anterior segment). No significant circumferential variability was detected. Compared with previous studied healthy subjects, TM patients showed strain values significantly lower in all the circumferential regions at each level (mean difference from 4 % to 13 %; P&lt;0.001 for all the comparisons). Segmental Ecc values were not significantly correlated with the correspondent T2* values and no correlation was detected considering the global values, averaged over all segmental values. Three groups identified on the basis of cardiac iron distribution: no MIO, heterogenous MIO and homogeneous MIO. The global ECC was comparable among the three groups (-11.56 ± 1.60 % vs -11.70 ± 2.43 % vs -11.14 ± 1.95 %; P=0.602). Global ECC values were not significantly correlated with age and were comparable between the sexes. Circumferential shortening was not associated to left ventricular (LV) volumes and ejection fraction (with a P&gt;0.5 in all the comparisons). Conclusions TM patients showed a significantly lower cardiac contractility compared with healthy subjects, but this altered contractility was not related to cardiac iron, volumes and function. Disclosures: No relevant conflicts of interest to declare.

Diabetes mellitus and cardiac complications in thalassemia major patients

Background The relationship between diabetes mellitus (DM) and cardiac complications has never been systematically studied in thalassemia major (TM). The aim of this crosssectional study was to evaluate in a large historical cohort of TM in the cardiovascular magnetic resonance (CMR) era if DM was associated with an higher prevalence and risk of heart complications, also regardless to the presence of myocardial iron overload (MIO). Methods We compared 86 TM patients affected by DM with 709 TM patients without DM enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network at their first CMR. The MIOT network involves 68 thalassemia centers and 8 CMR sites where the exams are performed using standardized and validated procedures and all centers are linked to a web-based database to collect and share patients’ history, clinical and diagnostic data. Cardiac iron was evaluated by T2* multiecho multislice technique. Biventricular function parameters were quantitatively evaluated by cine images. Myocardial fibrosis was evaluated by late gadolinium enhacement CMR technique. Heart failure (HF) was diagnosed by CMR in presence of a left ventricular (LV) and/or right ventricular (RV) ejection fraction (EF) lower than 4 standard deviations from the mean value normalized by sex and age. Moreover HF was identified by patients’ history, diagnosed by clinicians based on symptoms, signs and echocardiographic findings. All considered cardiac events were developed after the DM diagnosis. Results In DM patients versus no-DM patients we found a significantly higher prevalence of cardiac complications (HF, arrhythmias and pulmonary hypertension) (46.5% vs 16.9%, P<0.0001), HF (30.2% vs 11.7%, P<0.0001), hyperkinetic arrhythmias ECG documented and requiring medications (18.6% vs 5.5%, P<0.0001), and myocardial fibrosis (29.9% vs 18.4%, P=0.008). To evaluate the impact of the DM on cardiac complications also in relationship to MIO, we always adjusted the risk of cardiac findings for the absence of MIO (all segments with T2*≥20 ms). Patients with DM had a significant higher risk of cardiac complications (OR 2.84, P<0.0001), HF (OR 2.32, P=0.003), hyperkinetic arrhythmias (OR 2.21, P=0.023) and myocardial fibrosis (OR 1.91, P=0.021). Conclusions DM increases the risk for cardiac complications, HF, hyperkinetic arrhythmias and myocardial fibrosis irrespective of MIO. Funding “No-profit” support by industrial sponsorships (Chiesi, Apotex and GE Healtcare) and “Ministero della Salute, fondi ex art. 12 D.Lgs. 502/92 es .m.i., ricerca sanitaria finalizzata anno 2006” e “Fondazione L. Giambrone”.

Prospective Comparison on Cardiac and Hepatic Iron and Cardiac Function by MR in Thalassemia Major Patients Treated with Combination Deferiprone–Desferrioxamine Versus Deferiprone and Desferrioxamine in Monoterapy,

Abstract 3194 Introduction:Using T2* Magnetic Resonance (MR) a randomized placebo controlled study from Sardinia demonstrated combination therapy with deferiprone and desferrioxamine (DFP+DFO) significantly more effective than DFO in improving myocardial iron. One non-randomized study from Sardinia and one observational study from Greece seem to confirm for DFP+DFO therapy the most rapid clearance of cardiac iron. No data are available in literature about prospective comparisons on cardiac iron and function and liver iron in TM patients treated with DFP+DFO versus DFP and DFO in monotherapy. The aim of our multi-centre study was to assess prospectively in a large clinical setting the efficacy of the DFP+DFO versus DFP and DFO in TM patients by quantitative MR. Methods:Among the 1135 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we selected those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans We evaluated prospectively the 51 patients treated with DFP+DFO versus the 39 patients treated with DFP and the 74 patients treated. Iron overload was measured by T2* multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results:The dosages were: combined therapy DFP 61.9±24.3 mg/kg per 6.1±1.4 days/week and DFO 40.7±6.0 per 3.5±1.1 days/week; DFP 73±13 mg/kg per 6.1±1.4 days/week; DFO 40.7±6.5 per 5.4±0.93 days/week. Excellent/good levels of compliance were comparable in the DFP+DFO (90.2%) versus DFP (94.9%) and DFO (95.9%) groups. The percentage of patients who maintained a normal global heart T2* value (≥20 ms) was comparable between DFP+DFO (96%) versus (100%) and DFO (98.1%) groups. Among the patients with myocardial iron overload at baseline (global heart T2*<20 ms), in all three groups there was a significant improvement in the global heart T2* values (combination: P=0.001; deferiprone: P=0.015 and desferrioxamine: P=0.007) and a significant reduction in the number of segments with an abnormal T2* value (combination: P=0.004; deferiprone: P=0.012 and desferrioxamine: P=0.002). Only in the deferiprone group there was a significant improvement in the left ventricular (LV) ejection fraction (EF) (P=0.045) while improvement in the right ventricular (RV) EF was significant in both combination (P=0.024) and deferiprone (P=0.001) groups. The changes in the global heart T2* as well as in biventricular function were not significantly different in DFO+DFP versus DFO or DFP groups (Table 1). After correction for influential covariates statistically different at baseline (global heart, age and HIC), the changes in global heart T2* values between the combination and the desferrioxamine groups became statistically different (P=0.014). Among the patients with hepatic iron at baseline (T2*<9.2 ms), the improvement in the liver T2* values was significant in the combination and in the desferrioxamine groups (combination: 4.9±6.0 ms P<0.0001; deferiprone: 2.1±4.8 ms P=0.070 and desferrioxamine: 2.0±3.5 ms P=0.010). The increase in liver T2* values was higher in combination versus deferiprone group, with a P-value near to the statistically significance (P=0.062); after covariates adjustment for the variable statistically different at baseline (serum ferritin) the significance was reached (P=0.043). The increase in liver T2* values was significant higher in combination than in desferrioxamine group (P=0.008), even after covariates adjustment.Table 1Inter-treatment (DFP+DFO vs DFP and DFP+DFP vs DFO) comparisons in terms of changes between the two MRs in patients with global heart T2* <20 ms.PDFP (n=9)DFP+ DFO (n=26)DFO (n=21)PMean Diff Global Heart T2* (ms)0.107+8.8 ± 8.6+4.5 ± 6.1+3.7 ± 5.50.644Mean Diff N seg. With T2* < 20 ms0.100−6.0 ± 5.6−2.4 ± 3.8−2.9 ± 3.70.638Mean Diff Mid-Septum T2* (ms)0.295+6.1 ± 7.4+3.3 ± 7.12.9 ± 5.60.841Mean Diff LV EF (%)0.181+5.0 ± 6.4+1.5 ± 6.7+2.0 ± 6.50.802Mean Diff RV EF (%)0.137+6.8 ± 3.7+3.2 ± 6.7+0.2 ± 8.80.187 Conclusions:Prospectively in TM patients at the dosages used in the clinical practice combined DFP+DFO showed superior reduction in myocardial iron only versus the DFO in monotherapy and it did not show better improvement in biventricular function in comparison to DFO and DFP monotherapy. On the other hand, combined DFP+DFO was significantly more effective in the reduction of the liver iron versus DFO and DFP in monotherapy. Disclosures:Pepe:Novartis: Speakers Bureau; Apotex: Speakers Bureau; Chiesi: Speakers Bureau. Off Label Use: Association of two chelators commercially available in order to obtain a higher efficacy.

A MRI Prospective Survey on Cardiac and Hepatic Iron and Cardiac Function in Thalassemia Major Patients Treated with Sequential deferiprone–desferrioxamine versus Deferasirox

Abstract 1087 Introduction:No data are available in literature about possible different changes in cardiac and hepatic iron and in cardiac function in thalassemia major (TM) patients treated with sequential deferipron–desferrioxamine (DFP-DFO) versus deferasirox (DFX). Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluated quantitatively this issue.Our aim was to prospectively assess the efficacy of the DFP-DFO vs DFX in a large cohort of TM patients by quantitative MR. Methods:Among the first 1135 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, 392 patients performed a MR follow up study at 18 ± 3 months according to the protocol. We evaluated prospectively 35 patients treated with DFP-DFO versus 80 patients treated with DFX between the 2 MR scans. Cardiac iron was evaluated by T2* multiecho multislice technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron was measured by T2* multiecho technique. Results:Excellent/good levels of compliance were similar in the two groups (DFP-DFO 97.1% vs DFX 98.8%; P=0.544).Among the patients with no significant myocardial iron overload (MIO) at baseline (global heart T2*≥20 ms), there were no significant differences between groups to maintain the patients without myocardial iron overload (DFP-DFO 96% vs DFX 98%; P=0.536).Among the patients with MIO at baseline, in both groups there was a significant improvement in the global heart T2* value (DFP-DFO: 4.8±3.9 ms P=0.004 and DFX: 3.5±4.7 P=0.001) and a significant reduction in the number of pathological segments (DFP-DFO: −3.2±3.8 P=0.026 and DFX: −2.4±3.8 P=0.003). Only in sequential group there was a significant increment in the left and right ventricular ejection fractions (4.3±5.1% P=0.035 and 6.7±6.6% P=0.017, respectively). The improvement in the global heart T2* was not significantly different between groups. The improvement in the left as well in the right ventricular ejection fractions was significantly different between groups (P=0.009 and P=0.015, respectively) (Figure 1). [Display omitted] Among the patients with hepatic iron at baseline (T2*<9.2 ms), only in the DFX group there was a significant improvement in the liver T2* value (2.6±5.3 ms P=0.001). The changes in liver T2* were significantly higher in DFX group than in DFP-DFO (0.5±2.0 ms) group (P=0.030) (Figure 2). [Display omitted] Conclusions:In TM patients prospectively no significant differences on cardiac iron were found between sequential DFP–DFO treatment versus DFX in monoterapy, although the DFP-DFO treatment was significantly more effective in improving biventricular global systolic function. Conversely, DFX was significantly more effective in reducing hepatic siderosis. Disclosures:Pepe:Novartis: Speakers Bureau; Apotex: Speakers Bureau; Chiesi: Speakers Bureau. Off Label Use: Association of two chelators commercially available in order to obtain a higher efficacy. Borgna-Pignatti:Apotex: Honoraria; Novartis: Honoraria, Research Funding.