Correlation between Changes in Cardiac Iron and Hepatic Iron in Pediatric Patients with Thalassemia Major

Introduction. A prospective magnetic resonance imaging (MRI) study demonstrated a good control of myocardial iron overload (MIO) in terms of prevention and treatment in children with thalassemia major (TM). The aim of the present study was to evaluate if changes in MIO were related to baseline hepatic iron or changes in hepatic iron overload (HIO). Methods. We considered 68 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) project with less than 18 years at the first MRI scan and who performed a follow-up (FU) study at 18±3 months. Myocardial and hepatic iron burdens were quantified by the T2* technique. The value of 20 ms was used as conservative normal value for the global T2* value. Liver T2* values were converted into liver iron concentration (LIC) values. A LIC<3 mg/g/dw indicated significant no HIO, between 3 and 7 mg/g/dw mild HIO, between 7 and 15 mg/g/dw moderate HIO, and ≥15 mg/g/dw severe HIO. Results. Thirty-six patients were females and mean age at the time of the baseline MRI was 13.74±3.09 years. Baseline global heart T2* values were 29.72±11.21 ms and 16 (23.5%) patients showed significant baseline MIO. The percentage changes in global heart T2* values per month in the whole patient population were 0.66±1.70 and they resulted significantly higher in the 16 patients with significant baseline MIO versus the patients with no baseline MIO (1.99±2.53% vs 0.25±1.09% ms; P=0.002). Percentage changes in global heart T2* values per month were not influenced by initial MRI LIC values (R=0.048; P=0.695) (Figure 1A) and were comparable among the 4 groups of patients identified on the basis of baseline MRI LIC values (14 no HIO: 0.29±1.12% vs 21 mild HIO: 0.75±1.56% vs 15 moderate HIO: 0.82±2.03% vs 18 severe HIO: 0.71±2.00%; P=0.876). Percentage changes in global heart T2* values per month were not associated to final MRI LIC values (R=-0.134; P=0.277) (Figure 1B). The correlation between % changes in global heart T2* and MRI LIC values did not reach the statistical significance (R=-0.244; P=0.067) (Figure 1C). In patients with baseline MIO no correlation was found between % changes in global heart T2* values per month and initial MRI LIC values (R=-0.325; P=0.219) or % changes in MRI LIC values per month (R=-0.353; P=0.180). Conclusion. In pediatric TM patients changes in cardiac iron are not correlated to baseline MRI LIC values and changes in hepatic iron. So, our data seem not supporting the hypothesis for which it is necessary to clean the liver before removing iron from the heart. Figure 1 Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

Download Full-text

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

Blood ◽

10.1182/blood.v118.21.1087.1087 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1087-1087

Author(s):

Alessia Pepe ◽

Antonella Meloni ◽

Giuseppe Rossi ◽

Domenico Giuseppe D'Ascola ◽

Marcello Capra ◽

...

Keyword(s):

Cardiac Function ◽

Iron Overload ◽

Right Ventricular ◽

Systolic Function ◽

Thalassemia Major ◽

Ventricular Ejection ◽

Hepatic Iron ◽

Myocardial Iron ◽

Liver Iron ◽

Cardiac Iron

Abstract 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). 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). 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.

Download Full-text

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..

Download Full-text

Reduction of Hepatic Iron in Patients with Thalassemia Major According to Iron Chelation Regime Assessed by MRI T2*

Blood ◽

10.1182/blood.v112.11.5410.5410 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5410-5410

Author(s):

Vassilios Ladis ◽

Giorgos Chouliaras ◽

Kirikos Zannikos ◽

Panagiotis Moraitis ◽

Eleni Berdoussi ◽

...

Keyword(s):

Statistical Significance ◽

Linear Regression Analysis ◽

Thalassemia Major ◽

Rate Of Change ◽

Hepatic Iron ◽

Iron Loading ◽

Liver Iron ◽

Cardiac Iron ◽

Iron Load ◽

Number Of Patients

Abstract In 212 thalassemia major patients, repeated assessments for cardiac and hepatic iron (LIC) assessed by Magnetic Resonance Imaging (MRI – T2*) have been performed. The chelation regimes were either desferrioxamine (DFO), deferiprone (DFP), combination of DFO and DFP (Comb) or deferasirox (DFX). In general over the last few years, tailoring of chelation therapy has been principally guided by the cardiac iron loading. As many patients had been found to have excess cardiac iron, the majority (48%) had been placed on Comb. Patients were grouped according to the degree of siderosis. A T2* of <1.6ms was regarded as heavy LIC, between 1.6–4.0 moderate, 4.1–9.0 mild and > 9.1 acceptable. Taking into account that the change in T2* is not necessarily linear with respect to time and as the overall time of exposure to DFO, DFP and Comb regimes was significantly greater than that with DFX it was unjustified to perform comparative analysis using the total time period of the patients who were on any of the non DFX regimes. Therefore, to compare the efficacy of the four regimes on LIC, we performed an analysis using student T test to assess the rate of change only between the first and second MRI in patients with comparable LIC according to each chelation regime with adjustment for overall time of exposure (Table 1). Using the same data and applying linear regression analysis (Table 2) we compared the effect of DFO to the other three regimes in the annual rate of increasing hepatic T2*. Only Comb is effective at all levels of hepatic iron loading in reducing the iron content. DFX is effective in the mildly iron loaded patients and for the moderately iron loaded patients, its efficacy approaches statistical significance. DFP does not seem to significantly decrease LIC at any level of hepatic iron load however the numbers of patients in that group are very small. Interestingly DFO seems the least effective at all levels of hepatic iron loading and particularly in the heavy loaded patients. This factor may be related to poor compliance to its use as the patients who have reached such levels of iron load are more often those who are not compliant. In the comparison analysis to DFO, only Comb is significantly better and DFP and DFX are equivalent to it. In addition Comb is more effective than DFX and DFP in that over 12 months it would increase the T2* by 3.8ms (p <0.001) and 3.9ms (p 0.012) respectively. DFX and DFP are similar in efficacy in that they maintain the liver iron at the same levels (DFP vDFX 0.009ms p=0.95). In patients with hepatic T2* >9ms, 4 of 11 on DFO, 5 of 6 on DFX, 7 of 11 on DFP and 3 of 22 on Comb fell below 9. It is of note that DFO only maintains LIC and that a number of patients in the normal range increased LIC. Taking this data into account the DFX and DFP results are compatible with those seen both in the clinic and in trials. It is apparent however that combination therapy is the most effective regime for reducing hepatic iron significantly. As with cardiac iron loading, by knowing the degree of hepatic iron loading by the non-invasive T2* measurement and being able to manipulate patients chelation regimes, it seems possible to be able to have patients free of excess hepatic iron and potentially reduce other iron related morbidities as well. Table 1 Annual estimated mean change in T2* according to severity of hepatic siderosis Regime Heavy Moderate Mild ΔT2* p ΔT2** p ΔT2* p *tm= mean time (in months) between MRI studies DFO n= 42 tm*= 24.6 0.05 0.5 0.57 0.37 0.1 0.7 DFP n= 11 tm= 23.8 0.56 0.25 0.88 0.31 3.5 0.19 Comb n= 101 tm=21.7 1.17 0.0064 3.6 <0.001 5.9 <0.001 DFX n=58 tm=15.2 3.1 0.11 1.25 0.06 3.8 0.014 Table 3 Mean estimated difference in T2* Standard Error p DFP v. DFO −0.7 1.6 0.7 Comb v DFO 3.1 1.05 0.03 DFX v DFO −0.7 1.2 0.5

Download Full-text

Prospective Survey on Heart and Liver Iron and Heart Function in Thalassemia Major Patients Treated with Sequential deferiprone–desferrioxamine Versus Deferiprone and Desferrioxamine in Monotherapy

Blood ◽

10.1182/blood.v118.21.5298.5298 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5298-5298

Author(s):

Alessia Pepe ◽

Antonella Meloni ◽

Giuseppe Rossi ◽

Anna Spasiano ◽

Domenico Giuseppe D'Ascola ◽

...

Keyword(s):

Cardiac Function ◽

Iron Overload ◽

Heart Function ◽

Thalassemia Major ◽

Left Ventricular ◽

The Other ◽

Hepatic Iron ◽

Myocardial Iron ◽

Liver Iron ◽

Biventricular Function

Abstract Abstract 5298 Introduction: Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluate quantitatively the changes in cardiac and hepatic iron and in cardiac function in thalassemia major (TM) patients under different chelation regimens. This study aimed to prospectively assess the efficacy of the sequential deferiprone–deferrioxamine (DFP-DFO) versus deferiprone (DFP) and deferrioxamine (DFO) in monotherapy 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. We evaluated prospectively the 35 patients treated with DFP-DFO versus the 39 patients treated with DFP and the 74 patients treated with DFO between the 2 MR scans. Iron concentrations were measured by T2* multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results: Excellent/good levels of compliance were similar in the DFP-DFO (97.1%) versus DFP (94.9%) and DFO (95.9%) groups. No significant differences were found in the frequency of side effects in DFP-DFO (15.6%) versus DFP group (9.4%). The percentage of patients who maintained a normal global heart T2* value (≥20 ms) was comparable between DFP-DFO (96%) versus DFP (100%) and DFO (98.1%) groups. Among the patients with myocardial iron overload (MIO) at baseline (global heart T2*<20 ms), in all three groups there was a significant improvement in the global heart T2* value (DFO-DFP: P=0.004, DFP: P=0.015 and DFO: ms P=0.007) and a significant reduction in the number of pathological segments (DFO-DFP: P=0.026, DFP: P=0.012 and DFO: P=0.002). In DFO-DFP and DFP groups there was a significant increment in the left ventricular (LV) ejection fraction (EF) (P=0.035 and P=0.045, respectively) as well as in the right ventricular (RV) EF (P=0.017 and P=0.001, respectively). The improvement in the global heart T2* and in biventricular function were not significantly different in DFO-DFP compared to the other groups (Table 1). Among the patients with hepatic iron at baseline (T2*<9.2 ms), only in DFO group there was a significant improvement in the liver T2* value (2.0±3.5 ms P=0.010). Liver T2*changes were not significantly different in DFO-DFP versus the other groups. Conclusions: Prospectively we did not find significant differences on cardiac and hepatic iron or in cardiac function in TM patients treated with sequential DFP–DFO therapy versus the TM patients treated with DFO or 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. Lai:Novartis: Honoraria, Research Funding.

Download Full-text

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,

Blood ◽

10.1182/blood.v118.21.3194.3194 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3194-3194

Author(s):

Alessia Pepe ◽

Antonella Meloni ◽

Pasquale Pepe ◽

Marcello Capra ◽

Domenico Giuseppe D'Ascola ◽

...

Keyword(s):

Iron Overload ◽

Left Ventricular ◽

Controlled Study ◽

Hepatic Iron ◽

Myocardial Iron ◽

Liver Iron ◽

Multi Centre Study ◽

Baseline Serum ◽

Cardiac Iron ◽

Biventricular Function

Abstract 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. 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.

Download Full-text

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

Blood ◽

10.1182/blood.v128.22.3631.3631 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3631-3631

Author(s):

Alessia Pepe ◽

Laura Pistoia ◽

Liana Cuccia ◽

Monica Fortini ◽

Vincenzo Caruso ◽

...

Keyword(s):

Iron Overload ◽

Iron Concentration ◽

Thalassemia Major ◽

Left Ventricular ◽

Ventricular Ejection ◽

Left Ventricular Ejection ◽

Myocardial Iron ◽

Liver Iron ◽

Biventricular Function

Abstract 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. 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..

Download Full-text

MRI Evaluation of Liver and Cardiac Iron Overload Impact on Hematopoietic Stem Cell Transplantation with β-Thalassemia Major

Blood ◽

10.1182/blood-2019-128903 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5738-5738

Author(s):

Libai Chen ◽

Yuelin He ◽

Jianyun Wen ◽

Wenjing Yang ◽

Xuan Liu ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Iron Overload ◽

Hematopoietic Stem Cell ◽

Serum Ferritin ◽

Iron Concentration ◽

Thalassemia Major ◽

Liver Iron ◽

Hematopoietic Stem ◽

Cardiac Iron

OBJECTIVE: To assess the effects of liver and cardiac iron overload detected by magnetic resonance imaging (MRI) T2* on hematopoietic stem cell transplantation in children with β-thalassemia major. METHODS:Summary of 380 cases of β-thalassemia major patients more than 5 years old in Nanfang hospital, southern medical university from 2012 to 2019.Iron concentrations in the liver and heart were calculated based on MRI T2* test results of liver and heart. Age, serum ferritin, left ventricular ejection fraction (LVEF), and liver function were compared to evaluate the effect of iron overload on organ function in patients with β-thalassemia major before transplantation.168 patients underwent allogeneic hematopoietic stem cell transplantation, 48 were HLA-mismatched transplantation, and 120 were HLA-identical allogeneic hematopoietic stem cell transplantation.To analysis the influence between implantation rate, hematopoietic reconstruction time, mortality, and common complications after transplantation such as graft-versus-host disease, hepatic venous obstruction, infection, immune hemolysis, and pancytopenia and liver and cardiac iron overload detected by magnetic resonance imaging (MRI) T2*. RESULTS:Myocardial iron overload occurred in 73 cases (19.2%), including 29 cases of cardiac T2*15~20 ms (mild), 23 cases of 10~14 ms (moderate), and 21 cases of <10 ms (severe).There were 305 cases (80.2%) with liver iron overload, including 98 cases with 2.7~6.3 ms (mild), 166 cases with 1.4~2.7 ms (moderate), and 41 cases with <1.4 ms (severe).LVEF decreased in 5 cases (1.6%).Liver iron was positively correlated with serum ferritin (r=0.523, P=0.001), cardiac iron concentration was positively correlated with serum ferritin (r=0.33, P=0.1), age was positively correlated with cardiac iron concentration (r=0.4, P=0.14), and age was negatively correlated with left ventricular ejection fraction (r=-0.36, P=0.001).After transplantation, liver iron concentration was positively correlated with hemoglobin implantation time (r=0.49, P=0.043), heart iron concentration was positively correlated with mortality (r=0.39, P=0.012), serum ferritin was negatively correlated with implantation rate (r=-0.26, P=0.012), and serum ferritin was positively correlated with infection incidence correlation (r=0.441, P=0.034).There were no statistically significant differences in liver, heart MRI T2*, liver iron concentration and heart iron concentration between the two groups before and after transplantation. CONCLUSION:Magnetic resonance imaging (T2*) is an effective and non-invasive method to detect the iron overload in the heart and liver caused by blood transfusion in β-thalassemia patients. Iron overload can have adverse effects on hematopoietic stem cell transplantation,and effective iron removal before transplantation can improve the success rate of transplantation.Quantitative assessment of iron overload in the liver and heart by MRI can be used as a necessary examination before transplantation. Disclosures No relevant conflicts of interest to declare.

Download Full-text

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.

Download Full-text

A T2* MRI Prospective Survey on Heart and Liver Iron In Thalassemia Major Patients Treated with Deferasirox Versus Deferiprone and Desferrioxamine In Monotherapy

Blood ◽

10.1182/blood.v116.21.4267.4267 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4267-4267

Author(s):

Alessia Pepe ◽

Giuseppe Rossi ◽

Antonella Meloni ◽

Maria Chiara Dell'Amico ◽

Anna Spasiano ◽

...

Keyword(s):

Iron Overload ◽

Conflicts Of Interest ◽

Thalassemia Major ◽

Mean Difference ◽

Cardiac Complications ◽

Myocardial Iron ◽

Liver Iron ◽

Multi Centre Study ◽

Cardiac Iron ◽

And Function

Abstract Abstract 4267 Introduction: Most deaths in thalassemia major (TM) result from cardiac complications due to iron overload. In thalassaemia available three iron chelation regimes in monotherapy may achieve different changes in cardiac iron and function and liver iron. No data are available in literature about prospective comparisons on cardiac iron and function and liver iron in TM patients treated with deferasirox (DFX) versus deferiprone (DFP) and desferrioxamine (DFO) in monotherapy. Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluated quantitatively this issue. The aim of this multi-centre study was to assess prospectively in the clinical practice the efficacy of the DFX versus DFP and DFO in monoterapy 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 the 193 TM patients who had been received one chelator alone between the 2 MR scans. We identified 3 groups of patients: 80 treated with DFX, 39 treated with DFP and 74 treated with DFO. Myocardial and liver iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results: 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). Among the patients with no significant myocardial iron overload at baseline (global heart T2* ≥ 20 ms) (DFX 54 pts, DFP 30 pts, DFO 53 pts), there were no significant differences in all 3 groups to maintain the patients without significant myocardial iron overload (DFX 98%; DFP 100%; DFO 98%; P=1.0) Among the patients with myocardial iron overload at baseline (global heart T2* < 20 ms) in all 3 groups there was a significant improvement in the global heart T2* value (DFX P=0.001, DFP P=0.015 and DFO P =0.007) and in the number of segment with a normal T2* value (DFX + 2.4 P=0.003, DFP +6.0 P=0.031 and DFO + 2.9 P=0.001); only in the DFP group there was a significant improvement in the right global systolic function (+ 6.8% P = 0.016). The improvement in the global heart T2* was significantly lower in the DFX versus the DFP group (P=0.0026), but it was not significantly different in the DFX versus the DFO group (mean difference global heart T2* 3.5 ± 4.7 ms versus 8.8 ± 8.6 ms and versus 3.7 ± 5.5 ms, respectively; P = 0.90) (see the figure). The changes in the mean serum ferritin level and in the global systolic bi-ventricular function were not significantly different among groups. In patients with liver iron overload at baseline (liver T2* < 5.1 ms), the change in the liver T2* was not significant among groups (mean difference liver T2*DFX 2.1 ± 4.2 ms vs DFO 1.9 ± 3.8 ms vs DFP 1.3 ± 3.3 ms; P = 0.9). Conclusions: Prospectively over 15 months in a large clinical setting of TM patients DFP monotherapy was significantly more effective than DFX in improving myocardial siderosis, no significant differences were found between DFX and DFO monotherapy. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

MRI-Guided Iron Assessment and Oral Chelator Use Improve Iron Status In Thalassemia Major Patients: a Six-Year Single Center Retrospective Cohort Study

Blood ◽

10.1182/blood.v122.21.563.563 ◽

2013 ◽

Vol 122 (21) ◽

pp. 563-563 ◽

Cited By ~ 1

Author(s):

Diana X Nichols-Vinueza ◽

Matthew T White ◽

Andrew J Powell ◽

Puja Banka ◽

Ellis J. Neufeld

Keyword(s):

Side Effects ◽

Iron Overload ◽

Research Funding ◽

Iron Status ◽

Iron Concentration ◽

Thalassemia Major ◽

Target Range ◽

Single Center ◽

Liver Iron ◽

Cardiac Iron

Abstract Background Patients (pts) with thalassemia major (TM) require regular red blood cell transfusions. Adequate iron chelation prevents morbidity and mortality due to transfusional iron overload, and must be guided by accurate assessment of tissue iron levels. Magnetic resonance imaging (MRI) can non-invasively measure liver iron content (LIC) and cardiac iron, and has almost entirely supplanted liver biopsy for LIC at our center. The therapeutic goal is to either (a) maintain iron status within a consensus target range, or (b) decrease the iron burden in pts above the target. Three chelators are FDA approved in the US: deferoxamine (DFO), deferasirox (DFX), and deferiprone (DFP), (approval years 1968, 2005 and 2011 respectively). The aim of this study was to evaluate our ability to improve iron status over time in the MRI and oral chelator era. Methods This IRB-approved, single-center, retrospective observational study covered the period from Jan 2005, when MRI iron assessments became standard at our center, to Dec 2012. The study population included all TM pts followed for chelation at our center who had >2 MRI studies during the study period. LIC was measured by calculating T2* and, starting April 2006, also by measuring T2 using the commercial Ferriscan® technique. Liver T2* was converted to LIC using a regression equation (Wood et al. Blood, 2005; 106:1460). Cardiac iron concentration was measured by calculating cT2*; in this abstract both T2* in msec and its reciprocal R2* (1000/cT2* in Hz, which varies proportionally to iron) are reported. The target for LIC was <7 mg/g dry wt (dw), (mean of T2* and Ferriscan LIC) and for cardiac iron, cR2*<50 Hz (i.e. cT2* >20 msec). Statistical analyses were performed in SAS. Results 42 pts (55% male) met the inclusion criteria and had a median age at first MRI of 17.5y (range 1.9-43). Over a mean follow-up period of 5.2±1.9 y, 190 MRIs were performed with median of 4.5 MRIs per pt, interquartile range 3-6. In 2005, DFO was the predominant chelator (70% vs 26% on research use of chelators, DFX; n=27); DFX predominated after its commercial launch. 29/40 (73%) were on DFX by 2009, but this proportion dropped to 23/36 (64%) by 2012. 13/42 pts (31%) remained within the target ranges for cardiac T2* and LIC throughout the study period. 29/42 pts (69%) had at least one cardiac T2* or LIC out of the target range in a total of 97 MRIs. 38/97 (40%) of these out-of-range MRIs prompted a change in chelation strategy: 61% dose change only, 34% change of monotherapy agent, and 5% change from monotherapy to combination. Two pts died of heart failure due to iron overload during the study period; both had taken DFP before their deaths, but for divergent duration (3 days vs 5 y). The median number of chelation changes was 1.4 per pt/y (IQR 0.9-1.9). 175/229 (76%) dosing changes were for iron status as assessed by MRI or ferritin; 7/229 (3%) were dose decreases for side effects, and 2% were due to weight change only. Change in chelators occurred 82 times during the study. 34% of chelator changes were due to low or high iron status by MRI or Ferritin. 11% of changes were for side effects to a prior chelator and 54% were for other reasons (commercial launch of DFX or clinical trials). From initial to final MRI, both LIC and T2* status of our pts improved significantly (figure). At the initial MRI, 16/41 (40%) of pts were in target range for both LIC and cR2*, 4/41 (10%) were in the highest (undesirable) range of LIC>15 mg/g dw, and/or cardiac T2* <10 msec. From first to last cardiac T2* assessment (n=38), 63% of pts started and ended within the target range, 13% improved from abnormal to target range, 24% remained out of the target range. The two pts who died were among the persistent abnormal cardiac T2* group. For LIC (n=42), 45% remained in the target range throughout, 33% started out of target range and ended within, 12% improved but not to the target, 7% worsened, and one outlier remained severe. Conclusions The introduction of routine MRI assessments of LIC and cardiac R2* (T2*), together with the introduction of oral chelators, has improved the fraction of TM pts with liver and cardiac iron within the target range at our center. Annual MRIs facilitate chelation changes when necessary. Legend: A: Cardiac iron status from first to last MRI for each subject. Reciprocal cR2* and cT2* are on left and right Y-axes. B: Liver iron status. P-values are by Wilcoxon signed-rank test. Disclosures: Neufeld: Shire: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Apopharma: Consultancy.

Download Full-text