Multi-echo Dixon and breath-hold T2-corrected multi-echo single-voxel MRS for quantifying hepatic iron overload in rabbits

Background Three-dimensional (3D) multi-echo-Dixon (ME-Dixon) and breath-hold T2-corrected multi-echo single-voxel MR spectroscopy (HISTO) can simultaneously quantify liver fat and liver iron. However, their diagnostic efficacy and application scope for quantitative iron in co-existing fatty liver have not been adequately evaluated. Purpose To evaluate the accuracy of ME-Dixon and HISTO for quantitative analysis of hepatic iron in rabbits with iron deposition and fatty liver using liver–iron concentration (LIC) as a reference standard. Material and Methods ME-Dixon, HISTO, and conventional two-dimensional multi-echo gradient echo (GRE) sequences were performed on 42 rabbits. The following parameters were calculated: R2* from ME-Dixon and GRE; proton density fat fraction (PDFF) from the ME-Dixon, HISTO (normal TE range), and HISTO-H (extended TE range); and R2_water from HISTO and HISTO-H. The LIC and liver–fat concentration (LFC) were measured through chemical analysis, and their relationship with the MRI parameters were assessed. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate the diagnostic efficiency. Results LIC was significantly correlated with R2_HISTO-H, R2*_Dixon, and R2*_GRE ( r = 0.858, 0.910, 0.931, respectively; P < 0.001) and weakly with R2_HISTO ( r = 0.424; P = 0.008). A strong correlation was also observed between the LFC and PDFF obtained from HISTO, HISTO-H, and ME-Dixon ( r = 0.776, 0.811, 0.888, respectively; P < 0.001). ME-Dixon showed the best performance with moderate iron overload (AUC = 0.983). Conclusion 3D ME-Dixon is useful for quantifying the LIC, especially with co-existing fatty liver. Its diagnostic performance is also superior to that of the HISTO sequence.

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Myocardial iron overload

The EACVI Textbook of Cardiovascular Magnetic Resonance ◽

10.1093/med/9780198779735.003.0033 ◽

2018 ◽

pp. 364-374

Author(s):

John P Carpenter ◽

John C Wood ◽

Dudley J Pennell

Keyword(s):

Heart Failure ◽

Iron Overload ◽

Iron Concentration ◽

Left Ventricular ◽

Breath Hold ◽

Liver Iron ◽

Cardiac Iron ◽

Single Breath ◽

Developing Heart ◽

Cost Efficient

The heart is the target lethal organ in thalassaemia major. Cardiovascular magnetic resonance (CMR) measures iron using the magnetic relaxation time T2*. This allows comparison with the left ventricular function and conventional iron measurements such as liver iron and serum ferritin. The single breath-hold cardiac-gated CMR acquisition takes only 15 seconds, making it cost-efficient and relevant to developing countries. Myocardial T2* of <20 ms (increased iron) correlates with reduced left ventricular ejection fraction, but poor correlation exists with ferritin and liver iron, indicating poor capability to assess future risk. Myocardial T2* of <10 ms is present in >90% of thalassaemia patients developing heart failure, and approximately 50% of patients with T2* of <6 ms will develop heart failure within 1 year without intensified treatment. The technique is validated and calibrated against human heart iron concentration. The treatment for iron overload is iron chelation, and three major trials have been performed for the heart. The first trial showed deferiprone was superior to deferoxamine in removing cardiac iron. The second trial showed a combination therapy of deferiprone with deferoxamine was more effective than deferoxamine monotherapy. The third trial showed that deferasirox was non-inferior to deferoxamine in removing cardiac iron. Each drug in suitable doses can be used to remove cardiac iron, but their use depends on clinical circumstances. Other combination regimes are also being evaluated. Use of T2*, intensification of chelation treatment, and use of deferiprone are associated with reduced mortality (a reduction in deaths by 71% has been shown in the United Kingdom). The use of T2* and iron chelators in the heart has been summarized in recent American Heart Association guidelines.

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Myocardial and Hepatic Iron Overload and Cardiac Function In Sickle/Thalassemia Patients Of Italian Origin

Blood ◽

10.1182/blood.v122.21.2252.2252 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2252-2252

Author(s):

Antonella Meloni ◽

Giovan Battista Ruffo ◽

Daniele De Marchi ◽

Antonio Cardinale ◽

Anna Pietrapertosa ◽

...

Keyword(s):

Cardiac Function ◽

Iron Overload ◽

Conflicts Of Interest ◽

Iron Concentration ◽

Hepatic Iron ◽

Liver Iron ◽

Hepatic Iron Overload ◽

The Mean ◽

Magnetic Resonance Imaging Mri ◽

Italian Origin

Abstract Introduction Sickle-thalassemia results from the combined heterozygosity for sickle-cell and β-thalassemia genes. This study evaluates myocardial and hepatic iron overload and cardiac function in Italian patients and explores their correlation with transfusions, age and sex. Methods Fifty-nine sickle-thalassemia patients (29 males, mean age 35.6±14.1 years), enrolled in the MIOT network underwent magnetic resonance imaging (MRI). T2* value for all 16 myocardial segments and global heart T2* value were calculated. Hepatic T2* value was converted into liver iron concentration (LIC). Cine images were acquired to quantify biventricular volumes and ejection fraction (EF). Results 55 (93%) patients had all segmental T2* values normal (>20 ms). Of the 4 patients with abnormal segmental T2* values, all showed an heterogeneous myocardial iron overload (some segments with T2*>20 ms and other with T2*<20 ms) and only one had a global T2*<20 ms. The mean global heart T2* value was 34.4±6.2 ms. The mean LIC was 5.9±6.5 mg/g/dw and 30 patients (50.8%) had a pathological value (≥ 3 mg/g dw). There was a statistically significant positive correlation between global heart T2* and age but with poor linearity (R=0.368; P=0.004) and there was not a significant correlation between age and LIC. Males and females had comparable global heart T2* values and LIC values. Twenty patients were regularly transfused, 32 received sporadic transfusions while 7 were not transfused. The comparison among the three groups is shown in Table 1. We did not find significant differences in the global heart T2* value while patients regularly transfused had significantly higher LIC than sporadically transfused patients. Biventricular volumes indexed by body surface area and ejection fractions were comparable among the groups. Conclusions In respect of MIO, the sickle/thalassemia patients are similar to patients with homozygous SCD for which iron overloading is relatively rare. Hepatic iron overload may develop also in no regularly-transfused patients, maybe due to increased absorption of iron from the digestive tract, characteristic of both SCD and thalassemia intermedia patients. This finding underlines the importance to monitor by MRI also no regularly transfused sickle/thalassemia patients. Disclosures: No relevant conflicts of interest to declare.

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Hepatic iron load differs strikingly between peritoneal dialysis and hemodialysis patients

Bulletin de la Dialyse à Domicile ◽

10.25796/bdd.v2i4.23613 ◽

2019 ◽

Vol 2 (4) ◽

pp. 181-191

Author(s):

Guy Rostoker ◽

Mireille Griuncelli ◽

Nasredine Ghali ◽

Séverine Beaudreuil ◽

Yves Cohen ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Iron Overload ◽

Iron Concentration ◽

Dry Weight ◽

Hemodialysis Patients ◽

Hepatic Iron ◽

Dialysis Patients ◽

Liver Iron ◽

Iron Load ◽

Magnetic Resonance Imaging Mri

Introduction Iron overload is one of the most controversial topics in the management of anemic dialysis patients. Parenteral iron supplementation is commonly prescribed to hemodialysis (HD) patients but less frequently to peritoneal dialysis (PD) patients. Moreover, ferritin targets are far lower and more physiological in PD than in HD. Methods We compared the liver iron concentration (LIC) measured by means of Signal-Intensity ratio (SIR) magnetic resonance imaging (MRI) according to Rennes University method in a cohort of 32 PD patients living in the Paris region published in 2017, with two cohorts of French HD patients studied in the same way (119 patients reported in 2012 and 80 further patients reported in 2014). Results Normal hepatic iron load (LIC ≤ 50 µmol/g of dry weight) was observed in 81.3% of the 32 PD patients (CI: 64.3-91.5%), as compared to only 16% (CI: 10.4-23.7%) in the first HD cohort and 35% (CI: 25.4-45.9%) in the second HD cohort (p<0.0001 for both comparisons; X2 test). Mild iron overload (50 < LIC ≤ 100 µmol/g) was found in 5 PD patients and severe overload (LIC > 200 µmol/g) in only one PD patient (who had received IV iron) (3.1%; CI: 0-17.1%). Conversely, severe iron overload was found in 30.3% of patients in the first HD cohort (CI: 22.7-39%) and 11.3% of those in the second HD cohort (CI: 5.8-20.2%) (p= 0.0033 versus the first HD cohort, X2 test). Conclusion Contrary to hemodialysis patients, iron overload is rare and mostly mild in peritoneal dialysis patients.

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Central Role of LIC-R2 (Ferriscan®) Determination in Patients with Hemoglobinopathies: Licnet Experience

Blood ◽

10.1182/blood.v124.21.4034.4034 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4034-4034

Author(s):

Giuseppina Calvaruso ◽

Angela Vitrano ◽

Francesco Gioia ◽

Filippo Cassarà ◽

Saveria Campisi ◽

...

Keyword(s):

Iron Overload ◽

Iron Concentration ◽

Hepatic Iron ◽

Liver Iron Concentration ◽

Altman Plot ◽

Liver Iron ◽

Concentration Difference ◽

Hepatic Iron Overload ◽

Transfusion Requirements ◽

Secondary Endpoints

Abstract The main cause of mortality in the thalassemia population remains iron-induced cardiac failure (Borga-Pignatti et al Ann N Y Acad Sci 2005); in addition iron overload in the liver, pancreas and other organs causes progressive damage . Iron overload in human tissues can be treated by chelation therapy. Thus, early detection of iron overload is crucial. Nowdays liver iron overload in human tissues can be monitored noninvasively by magnetic resonance imaging (MRI) by two techniques, T2* and R2 MRI (Ferriscan®). There is not too much literature that compares the two methods in hemoglobinopathies. Our center instituted a network, LICNET (Liver Iron Cutino Network), promoted from Piera Cutino partnership and addressed to the diagnostics of iron overload in liver by R2 MRI in patients with hemoglobinopathies. Patients with thalassemia Major (TM), thalassemia intermedia (TI) and Sickle-Cell/b-thalassemia (S/b-T)), were retrospectively considered for this study. Primary endpoint was to evaluate agreement between T2* and R2 MRI measures of liver iron concentration (LIC) using a Bland-Altman (B-A) method that compares differences between observations on the same patient made with the two methods (Bland & Altman Lancet 1986). Secondary endpoints were to evaluate: 1) hepatic iron overload in our population; 2) difference in R2 LIC in patients with different chelation regimen; 3) relation between hepatic iron overload versus transfusion requirements. LIC was measured by calculating T2* and by measuring R2 using commercial Ferriscan® technique (St Pierre TG et al Blood 2005). To convert liver T2* to LIC a regression equation was used: LIC T2*=0.0254×R2*+0.202 (where R2*=1000/T2*) (Wood JC et al Blood 2005). LICNET involves 14 Italian thalassemia and radiology centers. Overall 301 adult patients with hemoglobinopathies (TM (177), TI (74) and S/b-T (50)) underwent to iron evaluation from 2012 to 2014. The mean age at R2 MRI evaluation was 33.2±10.7, 41.2±13.8 and 38.7±13.9, respectively in TM, TI and S/b-T. Iron overload was assessed in patients where most of the patients have been treated with deferasirox (DFX) therapy (TM (28.8%), TI (25.7%) and S/b-T (26.0%)), the remaining cohorts were treated with deferoxamine (DFO), deferiprone (DFP) chelation both alone and in combination or sequential administration. One hundred and twelve observations were measured both for T2* and R2. Concerning the primary endpoint, in the B-A plot it was observed that T2* method yielded a higher LIC than Ferriscan (differences>0), the estimated bias (estimated mean difference) was 2.6 (95% LoA – 17.8; 22.9), and this difference increased at high levels of iron content (Estim. Diff= -1.18+0.32Average mg/g/dw, p=0.0001) (Fig. 1). Secondary endpoints showed that hepatic iron overload determined by T2* was not statistically different among 3 cohorts of patients while it was border line by LIC-R2 (p=0.2608 and p=0.0672). Furthermore, DFX treated patients showed lower LIC-R2 determination in comparison with other treatment (Table 1). Finally, the increase of transfusion requirements was not associated with more severe iron overload in patients with TI and S/b-T. This may be in relation with compliance and type of chelation treatment. These findings show that LIC-R2 (Ferriscan®) is crucial to have accurate and reliable measures for iron body burden control in hemoglobinopathies. Table 1. Liver iron concentration determined by Ferriscan (R2) in patients with hemoglobinopathies treated by different chelation regimens. TM TI S/ b -T Chelation Therapy LIC R2 (mean±sd) LIC R2 (mean±sd) LIC R2 (mean±sd) DFO 5.3±5.7 8.5±7.7 20.9±19.9 DFP 12.9±12.3 12.5±8.1 12.7±20.2 DFX 7.6±9.2 6.1±7.1 3.7±3.2 Combined DFO+DFP 10.1±12.1 17.8 (n=1) --- Sequential DFO-DFP 4.3±3.1 --- --- Combined DFO+DFX --- 9.7 (n=1) --- Figure 1. Bland- Altman plot of Liver iron concentration: difference LIC T2* and LIC-R2 versus average of values measured by T2* and Ferriscan Figure 1. Bland- Altman plot of Liver iron concentration: difference LIC T2* and LIC-R2 versus average of values measured by T2* and Ferriscan Disclosures No relevant conflicts of interest to declare.

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Association Between Cardiac Iron Clereance and Hepatic Siderosis

Blood ◽

10.1182/blood.v128.22.4833.4833 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4833-4833

Author(s):

Alessia Pepe ◽

Laura Pistoia ◽

Domenico D'Ascola ◽

Maria Rita Gamberini ◽

Francesco Gagliardotto ◽

...

Keyword(s):

Iron Overload ◽

Iron Concentration ◽

Thalassemia Major ◽

Hepatic Iron ◽

Liver Iron Concentration ◽

Liver Iron ◽

Cardiac Iron ◽

Follow Up Study ◽

Hepatic Iron Overload

Abstract 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*. 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..

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Hepatic Steatosis, Rather Than Underlying Obesity, Increases the Risk of Infection and Hospitalization for COVID-19

Frontiers in Medicine ◽

10.3389/fmed.2021.636637 ◽

2021 ◽

Vol 8 ◽

Author(s):

Adriana Roca-Fernández ◽

Andrea Dennis ◽

Rowan Nicholls ◽

John McGonigle ◽

Matthew Kelly ◽

...

Keyword(s):

Fatty Liver ◽

Hepatic Steatosis ◽

Economic Status ◽

Liver Fat ◽

Secondary Outcome ◽

Proton Density ◽

Uk Biobank ◽

Risk Of Infection ◽

Liver Iron ◽

Increased Risk

Objective: Obesity is a risk factor for SARS-COV2 infection and is often associated with hepatic steatosis. The aim of this study was to determine if pre-existing hepatic steatosis affects the risk of infection and severity for COVID-19.Design: Prospective cohort study (UK Biobank). Univariate and stepwise multivariate logistic regression analyses were performed on liver phenotypic biomarkers to determine if these variables increased risk of testing positive and being hospitalized for COVID-19; then compared to previously described risk factors associated with COVID-19, including age, ethnicity, gender, obesity, socio-economic status.Setting: UK biobank study.Participants: 502,506 participants (healthy at baseline) in the UK Biobank, of whom 41,791 underwent MRI (aged 50–83) for assessment of liver fat, liver fibro-inflammatory disease, and liver iron. Positive COVID-19 test was determined from UK testing data, starting in March 2020 and censored in January 2021.Primary and Secondary Outcome Measures: Liver fat measured as proton density fat fraction (PDFF%) MRI and body mass index (BMI, Kg/m2) to assess prior to February 2020 using MRI of the liver to assess hepatic steatosis.Results: Within the imaged cohort (n = 41, 791), 4,458 had been tested and 1,043 (2.49% of the imaged population) tested positive for COVID-19. Individuals with fatty liver (≥10%) were at increased risk of testing positive (OR: 1.35, p = 0.007) and those participants with obesity and fatty liver, were at increased risk of hospitalization with a positive test result by 5.14 times (p = 0.0006).Conclusions: UK Biobank data revealed obese individuals with fatty liver disease were at increased risk of infection and hospitalization for COVID-19. Public policy measures and personalized medicine should be considered in order to protect these high-risk individuals.

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

Blood ◽

10.1182/blood.v124.21.4900.4900 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4900-4900

Author(s):

Antonella Meloni ◽

Aurelio Maggio ◽

Carlo Cosmi ◽

Alfonso D'Ambrosio ◽

Elena Facchini ◽

...

Keyword(s):

Iron Overload ◽

Iron Concentration ◽

Real Life ◽

Hepatic Iron ◽

Thalassemia Intermedia ◽

Liver Iron Concentration ◽

Liver Iron ◽

Cardiac Iron ◽

Hepatic Iron Overload ◽

Cardiac Iron Overload

Abstract 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. Figure 1 Figure 1. Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.

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Mild hepatic iron overload in dysmetabolic hyperferritinemia: MRI may overestimate the liver iron concentration values

Annals of Hematology ◽

10.1007/s00277-011-1346-5 ◽

2011 ◽

Vol 91 (6) ◽

pp. 961-961 ◽

Cited By ~ 2

Author(s):

Agustin Castiella ◽

Jose M. Alustiza ◽

Eva Zapata ◽

Jose I. Emparanza ◽

Pedro Otazua ◽

...

Keyword(s):

Iron Overload ◽

Iron Concentration ◽

Hepatic Iron ◽

Liver Iron Concentration ◽

Liver Iron ◽

Hepatic Iron Overload

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Deferiprone Has a Dose-Dependent Effect on Liver Iron Concentration

Blood ◽

10.1182/blood.v126.23.2159.2159 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2159-2159 ◽

Cited By ~ 1

Author(s):

Alessia Pepe ◽

Tommaso Casini ◽

Liana Cuccia ◽

Francesco Sorrentino ◽

Rosamaria Rosso ◽

...

Keyword(s):

Iron Overload ◽

Iron Concentration ◽

Hepatic Iron ◽

Liver Iron Concentration ◽

Liver Iron ◽

Hepatic Iron Overload ◽

Group 2 ◽

Dose Dependent ◽

Dose Dependent Effect ◽

Group 1

Abstract 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 1. Evolution 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 dw 3-7 mg/g dw 7-15 mg/g dw ≥15 mg/g dw Baseline LIC <3 mg/g dw (N=31) 21 7 3 0 3-7 mg/g dw (N=22) 10 4 6 2 7-15 mg/g dw (N=14) 0 6 5 3 ≥15 mg/g dw (N=12) 1 0 5 6 Total at the FU 32 17 19 11 DFP dose > 75 mg/kg/d (N=39) FU LIC <3 mg/g dw 3-7 mg/g dw 7-15 mg/g dw ≥15 mg/g dw Baseline LIC <3 mg/g dw (N=9) 6 2 1 0 3-7 mg/g dw (N=14) 3 11 0 0 7-15 mg/g dw (N=8) 0 4 4 0 ≥15 mg/g dw (N=8) 1 0 2 5 Total at the FU 10 17 7 5 Figure 1. Changes of MRI LIC values in patients with basal MRI LIC > 3 mg/g/dw. Figure 1. Changes of MRI LIC values in patients with basal MRI LIC > 3 mg/g/dw. Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc: Speakers Bureau; Novartis: Speakers Bureau.

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

Blood ◽

10.1182/blood.v124.21.4041.4041 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4041-4041

Author(s):

Antonella Meloni ◽

Aurelio Maggio ◽

Anna Pietrapertosa ◽

Pier Paolo Bitti ◽

Sabrina Armari ◽

...

Keyword(s):

Iron Overload ◽

Iron Concentration ◽

Iron Chelation ◽

Hepatic Iron ◽

Thalassemia Intermedia ◽

Liver Iron ◽

Cardiac Iron ◽

Number Of Patients ◽

Mri Scans ◽

Magnetic Resonance Imaging Mri

Abstract 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. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.

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