Improvement of Cardiac Function and Cardiac Volumes in Patients Treated with Deferasirox

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2159-2159
Author(s):  
Elena Cassinerio ◽  
Alberto Roghi ◽  
Patrizia Pedrotti ◽  
Laura Zanaboni ◽  
Francesca Brevi ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Iron Overload ◽  
Conflicts Of Interest ◽  
Iron Chelation ◽  
Myocardial Iron ◽  
Ventricular Volumes ◽  
Cardiac Morbidity ◽  
Cardiac Iron ◽  
Group A ◽  
Group B

Abstract Abstract 2159 INTRODUCTION. The iron chelation therapy in thalassemia major (TM) patients has been demonstrated to reduce cardiac morbidity and mortality. Deferoxamine (DFO) significantly improved survival but its use has several limitations due to reduced compliance. The once-daily oral chelator deferasirox (DFX) has been shown to remove iron from the liver and from the heart, with improved compliance. The efficacy of DFX in removing cardiac iron has been shown and significant improvements in myocardial T2* in patients with b-thalassemia with T2* levels < 20 ms have been demonstrated. The introduction in the clinical practice of the T2* Cardiac Magnetic Resonance (CMR) evaluation permitted a rapid, direct and highly reproducible method to assess myocardial and hepatic iron overload; moreover this technique allows to evaluate cardiac morphology and function. We evaluated the removal of cardiac iron and the cardiac function parameters in TM patients treated with DFX, undergoing CMR,followed at Hereditary Anemia Centre, Department of Internal Medicine in Milan. METHODS. Forthy-one TM patients (22 females, 19 males, mean age 32 ± 6 yrs), treated with DFX, followed in a single centre, underwent a CMR, performed at baseline (T0), after a variable period of exposure to DFX (median: 12 months, range 4–48 months) and then after at least 6 months of treatment (T1) (median 12 months, range 6–19 months). CMR was performed at Cardiology and CMR Department “A. De Gasperis” at Niguarda Ca' Granda Hospital in Milan, using a 1.5 Tesla MR scanner (Avanto Siemens, Erlangen). The signal intensity of this region was measured for each image with the use of commercial software (CMRtools, Cardiovascular Imaging Solutions, London, UK). All T2* analyses were performed blinded to patient details. Ventricular volumes were analyzed with the same software and stroke volume and ejection fraction calculated from end diastolic and end systolic ventricular volumes. Patients were divided in two groups: group A (28 patients) with baseline T2* values > 20 ms and group B (12 patients) with baseline T2* between 10 and 20 ms. RESULTS. In the overall population, the mean deferasirox dose was 26±7 mg/kg/day; dose adjustment was based on iron intake and on liver and cardiac iron overload at CMR. Despite different durations of deferasirox exposure and different levels of myocardial iron overload, an average improvement of myocardial T2* from 27.4 ms to 29.8 ms was observed at T1 (P=0.004). A significant improvement in LVEF from 63.6 % to 66.5 % (P=0.013), indicative of improved cardiac function, was also observed. Similarly, both end-systolic and end-diastolic ventricular volume assessments (EDV, EDVI, ESV, ESVI) showed significant improvement at T1. No difference in median serum ferritin levels were found between group A and B. Myocardial T2* increased in both groups with DFX treatment, with a significant improvement observed in Group B patients (T2* at T0 was 15.7 ± 2.7 ms and at T1 19.6 ± 3.8 ms, P=0.003) (Table 1). LVEF significantly increased in both groups, from 65.7% to 68.0 % in Group A (P=0.01) and from 59.7% to 64.3% in Group B (P=0.04) (Table 1). In Group A, improvements in EDV, ESV and ESVI were also significant with deferasirox treatment; in Group B significant improvements were observed in ESV and ESVI (Table 1). CONCLUSION. These data confirm the effects of iron chelation with deferasirox in removing cardiac iron in beta TM patients with mild-to-moderate myocardial iron overload and preventing accumulation of myocardial iron in patients with normal baseline cardiac iron levels. Interestingly, improvements in cardiac function were observed both in patients with and without myocardial iron overload at baseline, however it was more significant in patients with normal T2* at baseline. Disclosures: No relevant conflicts of interest to declare.

Onset of Cardiac Iron Loading in a Large and Homogeneous Cohort of Thalassemia Major Paediatric Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2157-2157
Author(s):  
Alessia Pepe ◽  
Antonella Meloni ◽  
Brunella Favilli ◽  
Marcello Capra ◽  
Domenico Giuseppe D'Ascola ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Conflicts Of Interest ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Myocardial Iron ◽  
Cardiac Iron ◽  
Paediatric Patients ◽  
Biventricular Function ◽  
Significant Difference

Abstract Abstract 2157 Introduction: Magnetic Resonance Imaging (MRI) by the T2* technique allows highly reproducible and non invasive quantifications of myocardial iron burden and it is the gold standard for quantifying biventricular function parameters. It is important to determine the appropriate age to start MRI screening, because its high cost. Few data are available in the literature and they are contrasting. So the aim of this study was to address this issue in our paediatric patients with thalassemia major (TM). Methods: We studied retrospectively 72 patients (47 males, 4.2–17.9 years old, mean age 13.03 ± 3.70 years), enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network. Myocardial iron overload was measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results: The global heart T2* value was 29.7 ± 11.2 ms (range 6.2 – 48.0 ms). No significant correlation was found between global heart T2* value and age (see figure). The global heart T2* value did not show significant differences according to the sex (male 30.2 ± 11.0 ms versus female 28.7 ± 11.8 ms, P=0.568). Sixteen patients (22%) showed an abnormal global heart T2* value (<20 ms) and none of them was under 8 years of age. Global heart T2* value was negatively correlated with mean serum ferritin levels. Odds Ratio for high serum ferritin levels (≥ 1500 ng/ml) was 8.4 (1.01–69.37, OR 95%CI) for abnormal global heart T2* values (< 20 ms). The global heart T2* value did not show a significant difference with respect to the chelation therapy (P=0.322). No significant correlations were found between the global heart T2* values and the bi-atrial areas or the LV and RV morphological and functional parameters. Eight patients showed a left ventricular (LV) ejection fraction (EF) < 57% and none of them was under 7 years of age. Two patients showed a right ventricular (RV) EF < 52% and none of them was under 14 years of age. Conclusion: The MRI screening for both cardiac iron overload and function assessment can be started for TM patients at the age of 7 years. At this age not sedation is generally needed. If the availability of cardiac MRI is low, the serum ferritin levels could be used as a discriminating factor. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽  
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.

Regional Myocardial Contractility In Thalassemia Major By Magnetic Resonance Tagging

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4708-4708
Author(s):  
Antonella Meloni ◽  
Chiara Tudisca ◽  
Emanuele Grassedonio ◽  
Giancarlo Izzi ◽  
Maddalena Lendini ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Iron Overload ◽  
Myocardial Contractility ◽  
Healthy Subjects ◽  
Conflicts Of Interest ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Myocardial Iron ◽  
Cardiac Iron ◽  
Biventricular Function

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<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>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.

Multidisciplinary Evaluation Improves Efficacy and Safety of Iron Chelation Therapy with Deferasirox in MDS Elderly Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4558-4558
Author(s):  
Lisette Del Corso ◽  
Elisa Molinari ◽  
Andrea Bellodi ◽  
Riccardo Ghio ◽  
Andrea Bacigalupo ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Group A ◽  
Group B

Abstract BACKGROUND: Iron overload from chronic transfusion therapy can be extremely toxic and most patients (pts) do not receive adequate iron chelation therapy (ICT) despite evidence of transfusional iron overload (IOL). Deferasirox (DFX) is the principal option currently available for ICT in the management of IOL due to transfusion dependent anemia, such as in MDS pts. The most common adverse events (AEs) are gastrointestinal disorders, skin rash, elevations in liver enzymes levels and non-progressive transient increases in serum creatinine also in MDS pts, most of whom are elderly with significant comorbidities and side effects of other concomitant therapies. In order to achieve effective ICT with minimal toxicity in individual pts, regular monitoring to assess IOL and adverse effects of DFX treatment is essential. METHODS: The safety and efficacy of DFX were examined in a retrospective multicenter observational study of transfusion-dependent (TD) MDS pts with International Prognostic Scoring System (IPSS) low-or Int-1-risk. We included all pts treated with DFX up to 12 months, divided into two groups; the first one (group A) not under a multidisciplinary assessment, including pts not adequately treated, in terms of dosing and discontinuation of ICT and the second one (group B) with pts under multidisciplinary control. The DFX starting dosing was 10 mg/kg/die in all pts. The aim of our retrospective analysis was to assess the effectiveness of ICT in relation of dosing and right management of AEs. RESULT: We evaluated 45 MDS pts (12F/33M); 27 belonging to the group A and 18 to group B. The age was 74.2±8.8 and 77.3±4.8 respectively. The ECOG 0-1 was 85,1% in group A and 88,9% in group B. The transfusion episodes prior starting DFX were22.1±12.1 and 24.5±35.4 in the first and in the second group, respectively. The serum ferritin level at baseline was respectively 1285.1±489.6 ng/mL and 1452.6±748.1 ng/mL. The mean serum ferritin level increased from 1285.1+489.6 ng/mL to 1412.1+842.8 ng/mL in group A while decreased from 1452.6+748.1 ng/mL to 1166.1+ 723.4 ng/mL in group B. The rate of inadequate therapy, in terms of dosing and/or discontinuation ICT, was 85% in group A compared to 60% in group B (p= 0.086).The rate of severe SAE observed in all pts was 10%.The most common AEs were diarrhea, nausea, upper abdominal pain, serum creatinine increase. The positive hematological response rate was observed in 15% of all pts. CONCLUSIONS: The study showed that group B obtained advantage in terms of efficacy and toxicity. The difference between the two groups derived from the ability to manage comorbidities, concomitant therapies and AEs, in particular the rise in serum creatinine, the most common cause DFX discontinuation or dosing reduction. In this setting, the most important specialist was the nephrologist. In our multidisciplinary group experts in management of ICT were hematologist, internist, immune-hematologist and nephrologist. We shared how we monitored kidney function and managed a possible nephrotoxicity (table.2), in order to ensure DFX efficacy. Positive hematological responses were observed, and a subset of pts achieved transfusion independence. The timing of future multidisciplinary evaluation is set on 24 and 36 months, time in which we expect the best response to DFX therapy. Table 1. Ferritin trend group A (n27) group B (n18) Ferritin N mean±SD Median (range) N mean±SD Median (range) Baseline 27 1285.1±489.6 1134 (388-2099) 18 1452.6±748.1 1515 (160-3018) 3 months 22 1451.5±720.5 1247.5 (529-2791) 13 1312.7±909.8 1064 (521-3859) 6 months 23 1850.5±1079.1 1419 (374-4185) 11 1168.4±648.4 1300 (160-2409) 12 months 17 1412.1±842.8 1372 (111-3127) 9 1166.1±723.4 930 (277-2536) Table 2. Management of renal changes during therapy with DFX Creatinine and urine examination:1) in two successive determinations prior to initiation of therapy, then every month 2) in pts with other risk factors for kidney disease, every week for 1 month after start of DFX or dose increase and, subsequently, every month Changes in creatinine:1) increased by 33% in two successive determinations: reduce DFX dose of 5 mg/kg 2) progressive increase of creatinine: interrupt DFX and then re-challenge it at a lower dose with gradual increase if the clinical benefits outweigh the risks Disclosures No relevant conflicts of interest to declare.

Deferasirox Improves Liver Pathology In β-Thalassemia Patients with Transfusional Iron Overload

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4274-4274 ◽  
Author(s):  
Yves Deugnier ◽  
Bruno Turlin ◽  
Victor Dong ◽  
Vanessa Giannone ◽  
Yiyun Zhang ◽  
...  
Keyword(s):  
Iron Overload ◽  
Success Rate ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Total Iron ◽  
Iron Chelation Therapy ◽  
Liver Pathology ◽  
Liver Iron ◽  
Group A ◽  
Group B

Abstract Abstract 4274 Background: While iron overload is known to cause hepatic toxicity, the effect of iron chelation therapy on liver pathology is not well understood. Data evaluating liver fibrosis during iron chelation therapy are limited to small studies (eg, Wu SF et al. Hemoglobin 2006 [n=17], Berdoukas V et al. Hematol J 2005 [n=49], Wanless IR et al. Blood 2002 [n=56]). In order to address such effects in a more robust patient population, we assessed liver biopsy samples from β-thalassemia patients enrolled in two large clinical studies (Porter J et al. Blood 2005, Cappellini MD et al. Blood 2006) that evaluated the effects of deferasirox on iron burden for up to 5 years. Methods: Patients with β-thalassemia and transfusional hemosiderosis receiving ≥8 blood transfusions/year, with liver biopsy assessment (defined as having either liver iron concentration [LIC], Ishak grading or Ishak staging assessment), after at least 3 years of deferasirox treatment, were included. Deferasirox dose was 5–40 mg/kg/day based upon level of iron overload (Study 107, patients randomized to deferoxamine [DFO] or deferasirox for the first year; Study 108, patients received deferasirox only). Treatment response success was defined according to baseline (start of deferasirox dosing) and end-of-study (EOS) LIC measurements (Table). Histological total iron score (TIS) was derived from the iron load observed in hepatocytes (hepatocytic iron score [HIS] range, 0–12), sinusoidal cells (sinusoidal iron score [SIS] range, 0–4) and main structures of the portal tracts (portal iron score [PIS]). A heterogeneity factor (H = 1, 2 or 3) was then applied, based on the overall appearance of the tissue, to provide TIS, calculated as (HIS + SIS + PIS) × (H/3) [range 0–60]. Hepatocytic to total liver iron ratio was calculated as HIS/(HIS + SIS + PIS) (Deugnier Y et al. Gastroenterol 1992). Fibrosis staging was performed according to Ishak scale from 0 (no fibrosis) to 6 (cirrhosis, probable or definite). Liver inflammation was assessed according to the Ishak necroinflammatory grading system with an overall scoring range from 0–18 (Ishak K et al. J Hepatology 1995). Results: Of 770 patients enrolled in the deferasirox studies, 219 with histological biopsy data at baseline and at the end of at least 3 years of treatment with deferasirox were eligible for analyses. Mean LIC was 15.7 ± 9.9 mg Fe/g dw and median serum ferritin was 2069 ng/mL (range 273–11698) at the start of deferasirox treatment. After at least 3 years of treatment, overall LIC success response rate was 63.8% (n=134), and mean LIC decreased by 5.5 ± 10.6 to 10.1 ± 8.2 mg Fe/g dw. Mean absolute change in TIS and liver iron ratio were -8.2 ± 13.3 and -2.1 ± 27.3, respectively. The range of Ishak necroinflammatory scores at baseline was 0–8 with a mean of 2.0 (2.2 in patients who met success rate criteria [Group A], 1.6 in patients who did not meet the success rate criteria [Group B]). At EOS the necroinflammatory score improved to a mean of 0.8 overall, and in both subgroups, with a mean relative change of -66% (69% in Group A and -61% in Group B). Overall 83.3% (n=175) [85.8% (n=115) in Group A, 78.9% (n=60) in Group B] of patients experienced either stabilization or improvement in their Ishak fibrosis score. Ishak staging remained stable (change of -1, 0 or +1) in 55.7% (n=122) of patients. Fifty-nine patients (26.9%) had an improvement in Ishak grading by a score of ≥2. Similar improvements were observed between Group A (26.1%, n=35) and Group B (30.3%, n=23). Conclusions: This is the first study to assess the effect of iron chelation therapy on liver pathology in a large cohort of iron-overloaded patients with β-thalassemia. In addition to reducing total iron burden, deferasirox led to an improvement in pathological markers of iron overload-induced liver damage in the majority of patients; 83.3% showed stabilization or improvement in Ishak fibrosis staging as well as an overall improvement in necroinflammatory score. These effects were similar in both patients who met the LIC success rate criteria and those who did not, suggesting that the observed effects may be at least partly independent of the drug's chelation effect. These findings are important as stabilization or regression of hepatic fibrosis in the face of chronic insult may prevent progressive liver disease. Disclosures: Deugnier: Novartis: Honoraria. Dong:Novartis: Employment. Giannone:Novartis: Employment. Zhang:Novartis: Employment. Griffel:Novartis: Employment. Brissot:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Prospective Comparison on Cardiac Iron and Liver Iron by MR In Thalassemia Major Patients Treated with Combination Deferipron–Desferrioxamine Versus Deferipron and Desferrioxamine In Monoterapy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5164-5164
Author(s):  
Alessia Pepe ◽  
Giuseppe Rossi ◽  
Antonella Meloni ◽  
Dell'Amico Maria Chiara ◽  
Marcello Capra ◽  
...  
Keyword(s):  
Iron Overload ◽  
Clinical Setting ◽  
Conflicts Of Interest ◽  
Mean Difference ◽  
Controlled Study ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Multi Centre Study ◽  
Cardiac Iron ◽  
Prospective Comparison

Abstract Abstract 5164 Introduction: Using T2* MR a randomised 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-randomised 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 this 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 first 739 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, 253 patients performed a MR follow up study at 18±3 months according to the protocol. We evaluated prospectively the 43 patients treated with DFP+DFO versus the 30 patients treated with DFP and the 66 patients treated with DFO between the 2 MR scans. Myocardial and liver iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results: The doses of the combination treatment were DFP 66±23 mg/kg/d for 6±1 d/w and DFO 41±7 mg/kg/d for 4±1 d/w, the dose of DFP was 73±16 mg/kg/d, DFO was 41±7 mg/kg/d for 5.5 d/w. Excellent/good levels of compliance were similar in the 3 groups (DFP+DFO 91% versus DFP 97% versus DFO 92%; P =0.76). Among the patients with no significant myocardial iron overload at baseline (global heart T2*≥20 ms), there were no significant differences between groups to maintain the patients without myocardial iron overload (DFP+DFO 90% versus DFP 100% versus DFO 100%; P = 0.053). Among the patients with myocardial iron overload at baseline (global heart T2*<20 ms), in all groups there was a significant improvement in the global heart T2* value (DFP+DFO P=0.0001, DFP P=0.001 and DFO P=0.003), in the number of segment with a normal T2* value (DFP+DFO P=0.0001, DFP P=0.031, DFO P=0.0001) and in the right global systolic function (DFP+DFO P =0.002, DFP P=0.031, DFO P=0.045). The improvement in the global heart T2* was significantly different among groups (mean difference global heart T2* DFP+DFO 6.6±6.5 ms, DFP 10.7±7.2, DFO 3.6±5.4; P=0.009). The improvement in the global heart T2* was significantly higher in the DFP+DFO versus the DFO group (P=0.017), but it was not significantly different in the DFP+DFO versus the DFP group (P = 0.36) (see the figure). The changes 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 significantly different among groups (mean difference liver T2* DFP+DFO 2.9±4.7 ms, DFP 2.3±5.8, DFO 2.9±4.9; P=0.91). Conclusions: Prospectively in a large clinical setting over 15 months in TM patients combined therapy DFP+DFO confirmed superior reduction in myocardial iron in comparison to DFO, but no significant differences were found versus DFP monotherapy. Disclosures: No relevant conflicts of interest to declare.

Magnetic Resonance T2* Measurement of Myocardial Iron Deposition in Sickle Cell Disease: Risk Factors and Relationship with Cardiac Function.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4604-4604
Author(s):  
Alexander Ngwube ◽  
Andrew Hardie ◽  
Luis Ramos-Duran ◽  
Joseph Schoepf ◽  
Ibrahim Shatat ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Transfusion ◽  
Cardiac Function ◽  
Iron Overload ◽  
Left Ventricular ◽  
Iron Deposition ◽  
Myocardial Iron ◽  
Cardiac Iron ◽  
Paravertebral Muscles ◽  
Cardiac Iron Overload

Abstract Abstract 4604 BACKGROUND Children with thalassemia major (TM) and sickle cell disease (SCD) receiving chronic blood transfusion are at risk of developing cardiac iron overload. Magnetic resonance imaging (MRI) has emerged as a non invasive tool for the direct measurement of myocardial iron deposition in these patients. Previous studies have shown that patients with TM develop significant myocardial iron deposition that correlates with transfusion burden and cardiac function. However, the prevalence of myocardial iron overload, the risk factors and its relationship with cardiac function in patients with SCD are not well known. OBJECTIVE To review the patterns of cardiac iron overload using cardiac MRI in our cohort of children with SCD. METHODS Cardiac MRI studies performed in children with SCD at a steady state from January 2009 to June 2009 at our institution were reviewed. We abstracted demographic and laboratory data and reviewed their transfusion history. These patients were receiving chronic blood transfusion every 3-4 weeks. All patients had been on chelation therapy desferrioxamine and/or deferasirox. In each patient, MR (1.5T Avanto™, Siemens) T2* measurements were performed in the interventricular septum, as well as in the paravertebral muscles as an internal control. Cardiac T2* value of 25-46 was considered normal as previously published. RESULTS A total of 20 patients with Hb SS (50 % male), with a mean age of 14 years were studied. The mean duration of blood transfusion was 9.5 ± 5.3 years. Seventeen patients (85%) were on chronic transfusion for stroke or abnormal TCD and three (15%) for other reasons such as recurrent pain crises and priapism. Overall, the mean cardiac T2* was 31.2 ± 6.6 ms in our patients. Mean T2* values in the myocardium were significantly lower than T2* values measured in the paravertebral muscles in the same patients (31.2 ± 6.6 versus 48.2 ± 5.1, p<0.05). Two patients (10%) had low cardiac T2* (17 and 22) indicating significant myocardial iron deposition. In addition, borderline low T2* values (26 each) were noted in two additional patients (10%) suggesting high myocardial iron deposition. There was a weak but not significant correlation between cardiac T2* and left ventricular end-diastolic volume (r=0.17), left ventricular ejection fraction (r=0.21) and right ventricular end-diastolic volume (r=0.37). Also, there was no statistically significant correlation between myocardial T2* and transfusional burden (r= -0.26), duration of transfusion (r= -0.35), serum ferritin (r= -0.4) and liver iron concentration by biopsy (r= -0.33) and liver T2* (r=0.04). CONCLUSION Our study shows that patients with SCD develop significant cardiac iron overload (low cardiac T2*) than previously reported. However, there was no significant correlation between cardiac T2* and parameters of ventricular function even in patients with high myocardial iron content. The lack of correlation between cardiac T2* and serum ferritin, liver iron content and transfusion burden in our cohort concurs with previous studies. Thus the risk factors for cardiac iron accumulation and its correlation with cardiac function in this patient population remain unclear. Further prospective studies are needed to understand the pathogenesis and the consequences of cardiac iron overload in patients with SCD. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽  
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.

Single ROI Versus Multislice T2* MRI Approach for the Quantification of Hepatic Iron Overload

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4263-4263
Author(s):  
Antonella Meloni ◽  
Antongiulio Luciani ◽  
Vincenzo Positano ◽  
Daniele De Marchi ◽  
Gianluca Valeri ◽  
...  
Keyword(s):  
Iron Overload ◽  
Healthy Subjects ◽  
Conflicts Of Interest ◽  
Ferritin Level ◽  
Hepatic Iron ◽  
Noninvasive Technique ◽  
Measurement Variability ◽  
Group A ◽  
The Mean ◽  
Group B

Abstract Abstract 4263 Introduction. Precise and effective measurements of iron overload in the liver, where iron deposition seems to be primarily noticeable (Noetzli LJ et al, Blood 2008), are important for the early diagnosis, treatment and follow-up of patients with hemochromatosis or hemosiderosi. T2* Magnetic resonance imaging (MRI) represents the most available noninvasive technique to assess hepatic iron content and shows a good correlation with biopsy results (Wood JC et al, Blood 2005). In the clinical practice, a single hepatic slice is acquired and T2* measurement is performed in a single region of interest (ROI) of the parenchyma (Pepe A et al, Eur J Haematol 2006). This approach may mask an heterogeneous iron distribution. Thus, the aims of this study were to set up a MRI acquisition technique for the detection of the iron burden in the whole liver and to evaluate the effectiveness of the single ROI technique. Methods. Five transverse hepatic slices were acquired by a T2* gradient-echo sequence in 101 thalassemia major (TM) patients (48 males, mean age 29 ± 8 years, mean serum ferritin level 1413 ± 1209 ng/mL, mean pre-transfusion hemoglobin 9 ± 1 g/dl.) and 20 healthy subjects. The T2* value was calculated in a single ROI defined in the medium-hepatic slice. Moreover, the T2* value was extracted on each of the eight ROIs defined in the functionally independent segments according to Couinaud classification. The mean hepatic T2* value was obtained by averaging all segmental values. Results. For patients the mean T2* values over segments VII and VIII were significantly lower than the other segments (P<0.0001) (figure 1). This pattern was substantially preserved in the two groups identified considering the T2* normal cut-off (Ramazzotti A. et al J Magn Reson Imaging 2009) (group A: single ROI T2* < 15.8 ms and group B: single ROI T2* ≥ 15.8 ms). All mean segmental T2* values as well as the mean hepatic T2* value were strongly correlated with the single ROI T2* value. After the application of a correction map based on T2* fluctuations in the healthy subjects, no significant differences were found in the segmental T2* values for the whole patient population (P=0.251), for both the previously defined groups (Group A: P = 0.073 and Group B: P=0.476) as well as for the Group A patients (N = 23) with chronic hepatitis (P=0.111). Conclusions. Hepatic T2* variations are low and due to artifacts and measurement variability. The single ROI approach can be adopted in the clinical arena, taking care to avoid the susceptibility artifacts, occurring mainly in segments VII and VIII. Disclosures: No relevant conflicts of interest to declare.

Osteopenia Is Commonly Present in Prepubertal Children with Severe Hb E/βthalassemia Despite Adequate Transfusion and Iron Chelation Therapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3830-3830 ◽  
Author(s):  
Vip Viprakasit ◽  
Pairunya Sawathiparnich ◽  
Tuangrat Sangpraypanm ◽  
Linda Weerakulwattana ◽  
Pornpimol Kiattisakthavee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Free T4 ◽  
Hb E ◽  
Severe Group ◽  
Group A ◽  
Group B ◽  
Marrow Expansion

Abstract Objectives: Previous studies showed that low bone mineral density (BMD) is highly prevalent in Hb E/βthalassemia, who received occasional transfusion. Concerning the clinical heterogeneity of this syndrome, we determine whether adequate transfusion and chelation therapy in severe cases with Hb E/β0 thalassemia could ameliorate this complication. Methods: 50 pre-pubertal patients, age from 8–13, were recruited after informed consent. 26 were classified as severe group using Thalassemia International Federation (TIF) criteria, while 24 were mild. In severe patients, each received transfusion every 3 weeks (12–15 ml/kg) to keep their pre-transfusion Hb at 10 g/dL and they received iron chelation either by deferioxamine (20–40 mg/kg/d) or deferaxirox (25–30 mg/kg/d). Demographic data and history of chelation therapy were recorded. Serum free T4, TSH, PTH, cortisol, 25-OH Vit D, osteocalcin, alkaline phosphatase, serum ferritin (SF), Ca and P were determined. We measured the BMD of lumbar spines (L2-L4) and total body using DEXA (Lunar, Prodigy) and adjusted for height-age (HA) and bone age (BA). WHO criteria for BMD was Z-score −1 to −2.5 = osteopenia and &lt; −2.5 = osteoporosis. Results: They were compound heterozygotes of Hb E with either codon 41/41 (50.6%), codon 17 (19%), IVS2#654 (14%), IVS1#1 (4%), IVS1#5 (3%) and codon 71/72 (2%) mutations. In severe group, 15 cases had poor compliance for chelation therapy (group A) (average SF; 6027 ± 2564 ng/ml) while 11 cases had good compliance (group B) (average SF; 2374.3 ± 189 ng/ml) and the ferritin level in mild group (group C) were 197 ± 89.4 ng/ml. There were no statistical significances among these three groups regarding baseline Hb, age and sex-distribution, weight, height and their corrected Z-scores for the standard of Thai children. Only the onset of anemia was significant lower in group C (5.4 ±1.8 yrs) compared to 2.12 ± 1.35 and 2.24 ± 2 yrs in group A and B respectively. All had normal free T4, TSH, PTH, Ca and P. As expected, 7 cases (78%) of group A with marked iron overload had osteopenia while one (7%) had osteoporosis. A strong invert correlation between BMD and serum ferritin in this group was observed. To our surprise, 6 out of 11 (54%) in group B and 14 out of 24 (58%) in group C also had osteopenia. However, there was no correlation between BMD and baseline Hb, ferritin and other clinical parameters in the group B and C. Conclusion: Low BMD in thalassemia might be resulted from ineffective erythropoiesis, bone marrow expansion and iron deposition in the bone marrow. In severe Hb E/βthalassemia, despite adequate transfusion, osteopenia and osteoporosis remain highly prevalent especially when iron overload is a co-factor. However, detecting this complication in a “so-call’ milder group was surprising since this group of patients was less anemia and rarely required blood transfusion. These suggest that several factors beside anemia and bone marrow expansion might play roles on developing this complication. Moreover, the current standard transfusion and chelation protocol might not be preventable our patients from bone complications and they were at a greater risk of fracture in adulthood. It will be of interest to investigate whether calcium and Vit D supplement with or without osteoclast inhibitors could prevent osteopenia in this highly common hereditary anemia.

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