Correlation of Serum Ferritin Levels with Liver and Heart Mri T2 and Liver Iron Concentration in Beta Thalassemia Intermediate Patients: A Contemporary Issue

Abstract Background: B-Thalassemia intermediate (B-TI) is a genetic disease that is milder than beta thalassemia major. The accumulation of iron in different organs causes tissue damage. The T2* magnetic resonance imaging (MRI) technique is currently the gold standard for iron load detection. However, it is expensive and needs an expert radiologist to report findings. Therefore, we conducted this study to determine an optimal cut-off value of ferritin in proportion to T2 MRI for early detection of cardiac and hepatic iron overload in patients with beta thalassemia intermediate. Methods: This cross-sectional study was conducted on 108 patients with B-TI who referred to tertiary Hospital, Shiraz University of Medical Sciences, Shiraz, Iran. Serum ferritin, hepatic and cardiac T2 MRI were assessed. The ROC curve was used to determine the sensitivity and specificity of cut-off value. Results: Serum ferritin levels showed a statistically significant negative correlation with T2 hepatic MRI (r= -0.290, P value=0.003) and positive correlation with LIC (r= 0.426, P value ˂ 0.001) in the patients with BTI. However, T2 cardiac MRI was not significantly correlated with serum ferritin levels (P value= 0.073).According to the analysis of ROC curves, the best cut-off value for ferritin to show early diagnosis of liver iron overload was 412 ng/ml. calculated sensitivities and specificities were 0.78 and 0.82 for T2 liver MRI and 0.76 and 0.86 for liver iron concentration (LIC) respectively. Conclusion: Serum ferritin levels of 412 ng/ml might be considered as a cut-off point to evaluate hepatic iron overload before using expensive, not readily available T2 MRI. This level of serum ferritin (around 500 ng/ml) could be considered for starting iron chelation therapy in patients with B-TI in areas where T2 MRI is not available. Disclosures No relevant conflicts of interest to declare.

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Discrepancy between Serum Ferritin and Liver Iron Concentration in a Patient with Hereditary Hemochromatosis – The Value of T2* MRI

Case Reports in Oncology ◽

10.1159/000507756 ◽

2020 ◽

Vol 13 (2) ◽

pp. 712-715

Author(s):

Mustafa A. Al-Tikrity ◽

Mohamed A. Yassin

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Ferritin Level ◽

Hereditary Hemochromatosis ◽

Iron Concentration ◽

Hfe Gene ◽

Liver Iron Concentration ◽

C282y Mutation ◽

Liver Iron ◽

T2 Mri

Primary hemochromatosis is an inherited disorder, and the homeostatic iron regulator (HFE) gene C282Y mutation is a common cause of hemochromatosis in Europe. We are reporting a case of a 56-year-old female known to have hemochromatosis with the HFE gene C282Y mutation with a serum ferritin level of 482 μg/L who underwent heart and liver T2* MRI which showed no evidence of iron overload – neither in the heart nor in the liver. This indicates that there is a discrepancy between serum ferritin and liver iron concentration by MRI and the superiority of T2* MRI in diagnosis and follow-up of iron overload in patients with hereditary hemochromatosis.

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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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Transient Elastography of Liver in Hb E Beta Thalassemia: A Novel Tool to Determine Hepatic Iron Overload?

Blood ◽

10.1182/blood.v126.23.3368.3368 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3368-3368

Author(s):

Debmalya Bhattacharyya ◽

Maitreyee Bhattacharyya ◽

Saswata Chatterjee ◽

Abhijit Chowdhury ◽

Pramit Ghosh

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Liver Stiffness ◽

Beta Thalassemia ◽

Hepatic Iron ◽

Hepatic Iron Overload ◽

Number Of Patients ◽

T2 Mri

Abstract Introduction: Transient Elastography (TE) of liver is a well established tool to measure liver stiffness, mainly used for assessment of hepatic fibrosis due to chronic hepatitis. Liver biopsy is the gold standard test for measurement of liver iron concentration (LIC) whereas T2* MRI is the best available non-invasive method for the same in thalassemia. We intended to use hepatic TE as an alternative cheaper tool to assess hepatic iron overload so that it can be applied to larger number of patients. Objective: To assess degree of liver stiffness by TE in patients with HbE beta thalassemia and correlate the findings with LIC calculation by T2* MRI of liver. Materials and Method: 53 patients with HbE beta thalassemia from the thalassemia clinic of Institute of Haematology and Transfusion Medicine, Medical College, Kolkata were enrolled for the study. Patients with known liver disease were excluded. Baseline data like HbE%, mutations, transfusion requirement, growth status, serum ferritin level etc were collected. All of them underwent TE of liver in the School of Digestive and Liver Diseases, IPGMER using the FibroScan Touch 502 machine (Di Marco et al, British Journal of Haematology, Volume 148,3, 476-479, February 2010). 20 randomly selected patients were also assessed by T2*MRI of liver for hepatic iron assessment at the same time. LIC calculation was done from T2* value (J S Hankins et al, Blood, 14 May 2009, Volume 113:20). Data were analyzed by SPSS software-19, IBM. Results: The patients with HbE beta thalassemia had a mean HbE level of 53.66 (±18.45) %. Common beta mutations [mostly IVS-1-5(G-C)] usually found in this part of India, were detected. Mean and median age of the study population was 24.11±13.11 years and 20 years, respectively. Median age of 1st transfusion was 11 years. 35.84% patients were non-transfusion dependent. 39/53 patients had facial deformity and growth retardation. Mean baseline hemoglobin was 7.10±0.76 gm/ dl. Mean serum ferritin level was 3183.66±338.45 ng/ml. TE showed 30.18 % patients had severe liver stiffness (Liver stiffness measurement, LSM >15 kPa) whereas 43.34% had minimum stiffness (LSM≤7 kPa). No significant statistical correlation was found between serum ferritin and LSM. 12/20 patients showed very high calculated LIC (>15 mg/g) and lower T2* value (<1.8 ms) whereas only 10% of them showed mildly elevated calculated LIC. Rest had intermediate LIC. Discussion: There is lack of data regarding hepatic iron overload in HbE beta thalassemia and so also from this part of India. There was a trend that higher the age, higher was the LSM irrespective of the serum ferritin level though not found statistically significant (Figure 1). Serum ferritin level was also not significantly correlated with the calculated LIC in those 20 patients assessed with T2* MRI. 2 patients with mildly elevated LIC had a high ferritin level. Preliminary report indicates that with increase in LSM there was increase in calculated LIC also. Statistical analysis revealed patients with LSM≥7.2 kPa had moderate or severe hepatic iron overload and thus undermine the need for routine T2*MRI. The cut off value signifies that patients with LSM<7.2 kPa might or might not have significantly high liver iron overload, so obviously to be assessed by T2*MRI (Table 1). Therefore use of TE may be an alternative preliminary diagnostic method to gauge hepatic iron overload in HbE beta thalassemia patients. It would be of more value in countries like India where T2* MRI facility is not yet feasible in many centers catering to huge number of HbE-beta thalassemia patients. However, further exploration with larger number of patients is necessary to establish association of LIC and LSM in a more robust way. Conclusion: In resource-poor countries like India, TE may be a relatively cheap tool to be used as a marker of hepatic iron overload in future. Table 1. Finding Cut off: ROC (TE-value and LIC categories), n=20 Positive if Greater Than or Equal Toa Sensitivity 1 - Specificity 2.3 1.00 1.00 3.4 1.00 .50 4.4 .94 .50 5.7 .88 .50 6.2 .83 .50 6.5 .77 .50 7.2 .77 .00 8.2 .72 .00 8.85 .66 .00 9.45 .61 .00 10.2 .55 .00 11.85 .50 .00 13.85 .44 .00 15.75 .38 .00 18.3 .33 .00 22.9 .27 .00 27.9 .22 .00 35.9 .16 .00 44.7 .11 .00 48.0 .05 .00 49.8 .00 .00 Table 2. The smallest cutoff value is the minimum observed test value minus 1, and the largest cutoff value is the maximum observed test value plus 1. LSM more than 7.2 had a sensitivity of 77.2 % and specificity of 100%. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

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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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Monitoring Cardiac Siderosis in Patients with Beta-Thalassemia Major on Various Chelation Regimens,

Blood ◽

10.1182/blood.v118.21.3177.3177 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3177-3177

Author(s):

Srikanth R. Ambati ◽

Rachel Randolph ◽

Kevin Mennitt ◽

Dorothy A Kleinert ◽

Patricia Giardina

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Iron Concentration ◽

Iron Chelation ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Liver Iron ◽

Beta Thalassemia Major ◽

Cardiac Siderosis ◽

Hepatic Iron Overload

Abstract Abstract 3177 Background: Patients with Beta-thalassemia major develop progressive iron overload in various organs. Cardiac siderosis is a major cause of mortality and morbidity in these patients, and also poses a significant treatment challenge. Methods: We have reviewed 101 beta-thalassemia major patients 39 Male (M) 62 Female (F) with a mean age of 27.9 (range: 2 to 60 years). All received regular transfusions to maintain pre transfusion Hb levels of 9 to10 gm/dl and all received iron chelation initially with deferoxamine (DFO) and subsequently treated with deferasirox (DFX) or deferiprone (DFP) in combination with DFO. Each patient was monitored yearly for iron excess by hepatic and cardiac magnetic resonance imaging (MRI) T2*. They were also assessed with monthly evaluations for liver and renal function (Bili, AST, ALT, BUN, Creatinine), serum ferritin, CBC (or weekly if on DFP), and urinalysis. Annual EKG, ECHO, hearing and vision testing and endocrine evaluations were also performed. The patients were grouped according to the severity of cardiac siderosis. Mild to moderate cardiac siderosis was defined as a T2* 12–20 msec and severe cardiac siderosis T2*≤ 11 msec. Annual studies were compared using paired student T test and repeated measures Analysis Of Variance (ANOVA) when necessary. Patient population: Twenty one of the 101 patients (7M and 14F) with a mean age of 30.6 yr, age range 15 to 56 yr, had abnormal cardiac T2* of <20 msec and three or more subsequent annual cardiac T2* measurements. Thirteen patients, 3 M 10 F with a mean age of 33 (range: 19 to 60), had severe cardiac siderosis and 8 patients, 3 M 5 F with mean age of 38 (range: 25 to 49), had mild-moderate cardiac siderosis. During the course of the observation their iron chelation therapy was optimized to reduce serum ferritin levels < 1500 μg/dl and to reduce or maintain liver iron concentration (LIC) ≤ 7 mg/gm dw. Data analysis: At the time of their first annual MRI study (baseline), 8 patients were on DFO of which 6 were switched to DFX, 13 patients were on DFX, 11 patients were dose escalated on DFX, and 4 patients were switched to combination chelation with DFO and DFP. At baseline, patients with severe cardiac siderosis had a mean cardiac T2* level = 7.4 ± 0.47 SEM (range: 4.6 to 11msec). Over the treatment course of 6 years annual cardiac T2* levels consistently improved and by 6 years cardiac T2* reached a mean level =14.3 ±1.5 SEM (range: 12 to 17 ms) (Fig 1). Those patients who at baseline had a mild to moderate cardiac siderosis with mean cardiac T2* of 14.6 ± 1.02 SEM (range: 12 to 19 msec) improved by 3 years of treatment when they achieved a mean cardiac T2* of 26.3 ± 3.4 SEM (range of 16 to 42 msec) (Fig 2). Liver iron concentration (LIC) was measured annually by MRI. Initially the majority, 16 out of 21 of patients, had hepatic iron overload LIC ≤ 10 mg/ gm dw of whom 56% (9 of the 16) had severe cardiac siderosis. 5 of 21 patients had a LIC > 15 mg/ gm dw of whom 80% (4 out of 5) patients had severe cardiac siderosis (Fig 3). Patients with LIC ≤10 mg/ gm dw had ferritin levels ranging from 166 to 3240 μg/ dl and patients with LIC >15 mg/ gm dw had elevated serum ferritin levels of 1180 to 17,000 μg/ dl. Patients with severe cardiac siderosis had mean MRI ejection fraction (EF)= 55.8% (range: 31 to 70%) while patients with mild to moderate cardiac siderosis had mean MRI EF= 60% (range: 53 to 66%). One patient with severe cardiac siderosis was recovering from symptomatic congestive heart failure. Conclusion: Cardiac siderosis can be noninvasively diagnosed utilizing MRI T2* techniques and subsequently to monitor treatment. The majority of patients improve cardiac T2* over time with optimal chelation therapy. Severe cardiac siderosis occurs even with mild to moderate hepatic iron overload. Left ventricular EF may not predict severe cardiac siderosis. Therefore it is important to annually monitor cardiac siderosis with MRI T2*. Disclosures: No relevant conflicts of interest to declare.

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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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Safety and Efficacy of High Dose Intravenous Desferoxamine for Reduction of Iron Overload Due to Chronic Transfusion in Sickle Cell Patients.

Blood ◽

10.1182/blood.v112.11.1430.1430 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1430-1430

Author(s):

Ram Kalpatthi ◽

Brittany Peters ◽

David Holloman ◽

Elizabeth Rackoffe ◽

Deborah Disco ◽

...

Keyword(s):

Serum Creatinine ◽

Iron Overload ◽

Sickle Cell ◽

Serum Ferritin ◽

Liver Tissue ◽

Iron Concentration ◽

P Value ◽

High Dose ◽

Liver Iron ◽

Iron Storage

Abstract Background: Patients with sickle cell disease (SCD) receiving chronic blood transfusions are at risk of developing iron overload and organ toxicity. Chelation therapy with either subcutaneous (SQ) desferoxamine (DFO) or oral deferasirox is effective in preventing and reducing iron overload but poses significant challenges with patient compliance. Intravenous (IV) infusions of high dose DFO (HDD) have been utilized in non compliant patients with heavy iron overload in small case series. We review our experience of high dose IV DFO in a large cohort of SCD patients with significant iron overload who are non compliant with SQ DFO. Methods: The medical records of SCD patients who received HDD in our center between 1993 and 2004 were reviewed. All of them were on chronic transfusion, had significant iron overload defined by serum ferritin > 1500 and/or liver iron concentration (LIC) more than 10 μg/g of liver tissue and were non-compliant with SQ DFO. All patients underwent annual ophthalmologic, hearing, pulmonary and cardiac evaluation. Demographic data, treatment details, serum ferritin levels, liver iron concentration (LIC), liver enzymes, renal function tests, audiogram and other relevant clinical data were collected. Results: There were 27 patients (19 males, 8 females), 19 patients were on transfusion for history of cerebrovascular accident, 5 for abnormal transcranial Doppler flow velocity, 2 for transient ischemic attack and one for recurrent pain crises. All continued to receive packed red blood cell transfusions aimed to keep HbS levels below 30 or 50% during this time. They were treated in-hospital with DFO 15 mg/kg/hr IV for 48 hrs every 2 weeks (20 patients), 3 weeks (4 patients) and 4 weeks (3 patients). The mean age at start of high dose regimen was 14.6 years (range 9–27 years). The mean duration of HDD treatment was 8.9 months (range 3–49 months). Fourteen patients had LIC determined by liver biopsy. Significant reductions in LIC were observed after HD (table I). This was more pronounced in patients who had higher LIC and received at least 6 months of HDD. Histological examination of liver biopsies revealed a decrease in the grade of liver iron storage. Four patients had portal triaditis initially which resolved after starting HDD therapy. Also there was significant improvement in liver enzymes (ALT, AST) after HDD. There was a trend in decreasing ferritin levels after HDD but this did not achieve statistical significance. All patients tolerated HDD without any major reactions. No audiologic or ophthalmologic toxicity or acute or chronic pulmonary complications were observed. Blood urea nitrogen remained normal in all patients after HDD but there was mild increase in serum creatinine. One patient had high serum creatinine (1.2 mg/dL) after two doses HDD. This patient had focal segmental glomeurosclerosis which was most probably the cause for the rise in creatinine. There was no significant increase in serum creatinine in our series when this patient was excluded. Conclusions: In our cohort of SCD patients we observed a significant decrease in liver iron burden with high dose IV DFO. Our patients tolerated the therapy well without any major toxicity. This regimen is safe and may be an option for poorly compliant patients with significant iron overload. In addition, combination of this regimen with oral iron chelators may be of benefit to patients with significant iron overload and organ dysfunction. Table 1: Laboratory characteristics of sickle cell patients before and after high dose IV DFO Parameter No. of Patients Mean (SD) prior to HDD Mean (SD)after HDD p Value* * Changes in mean levels analyzed using two-tailed Paired T Test with significant p value ≤ 0.05. SD – Standard deviation + See text Liver iron (μg/g of liver tissue ) 14 16864 (10903) 12681 (8298) 0.04 Liver iron min of 6 months of HDD (μg/g of liver tissue ) 8 18677 (8319) 9362 (4521) 0.01 Liver iron >10 mg & minimum 6 months of HDD (μg/g of liver tissue) 7 21181 (7054) 10092 (4443) 0.01 Grade of liver iron storage 14 3.57 (0.9) 3.07 (1) 0.05 Serum Ferritin (ng/mL) 27 3842 (2619) 3238 (1780) 0.06 Serum AST (IU/L) 27 54.1 (27.2) 44.6 (17.6) 0.04 Serum ALT (IU/L) 27 39.2 (36) 27.5 (14.2) 0.01 Blood urea nitrogen (mg/dL) 27 8.9 (2.9) 9.5 (4.3) 0.20 Serum Creatinine (mg/dL)+ 26 0.50 (0.1) 0.55 (0.2) 0.07

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Comparing the Value of Serum Ferritin, Transfusion History and Magnetic Resonance Imaging for the Prediction of Iron Overload In MDS and AML Patients Undergoing Allogeneic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v116.21.3493.3493 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3493-3493

Author(s):

Martin Wermke ◽

Jan Moritz Middeke ◽

Nona Shayegi ◽

Verena Plodeck ◽

Michael Laniado ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Iron Content ◽

Iron Concentration ◽

Transferrin Saturation ◽

Resonance Imaging ◽

Liver Iron Concentration ◽

Liver Iron ◽

Liver Iron Content ◽

Transfusion History

Abstract Abstract 3493 An increased risk for GvHD, infections and liver toxicity after transplant has been attributed to iron overload (defined by serum ferritin) of MDS and AML patients prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, the reason for this observation is not very well defined. Consequently, there is a debate whether to use iron chelators in these patients prior to allo-HSCT. In fact, serum ferritin levels and transfusion history are commonly used to guide iron depletion strategies. Both parameters may inadequately reflect body iron stores in MDS and AML patients prior to allo-HSCT. Recently, quantitative magnetic resonance imaging (MRI) was introduced as a tool for direct measurement of liver iron. We therefore aimed at evaluating the accurateness of different strategies for determining iron overload in MDS and AML patients prior to allo-HSCT. Serologic parameters of iron overload (ferritin, iron, transferrin, transferrin saturation, soluble transferrin receptor) and transfusion history were obtained prospectively in MDS or AML patients prior to allo-SCT. In parallel, liver iron content was measured by MRI according to the method described by Gandon (Lancet 2004) and Rose (Eur J Haematol 2006), respectively. A total of 20 AML and 9 MDS patients (median age 59 years, range: 23–74 years) undergoing allo-HSCT have been evaluated so far. The median ferritin concentration was 2237 μg/l (range 572–6594 μg/l) and patients had received a median of 20 transfusions (range 6–127) before transplantation. Serum ferritin was not significantly correlated with transfusion burden (t = 0.207, p = 0.119) but as expected with the concentration of C-reactive protein (t = 0.385, p = 0.003). Median liver iron concentration measured by MRI was 150 μmol/g (range 40–300 μmol/g, normal: < 36 μmol/g). A weak but significant correlation was found between liver iron concentration and ferritin (t = 0.354; p = 0.008). The strength of the correlation was diminished by the influence of 5 outliers with high ferritin concentrations but rather low liver iron content (Figure 1). The same applied to transfusion history which was also only weakly associated with liver iron content (t = 0.365; p = 0.007). Levels of transferrin, transferrin saturation, total iron and soluble transferrin receptor did not predict for liver iron concentration. Our data suggest that serum ferritin or transfusion history cannot be regarded as robust surrogates for the actual iron overload in MDS or AML patients. Therefore we advocate caution when using one of these parameters as the only trigger for chelation therapy or as a risk-factor to predict outcome after allo-HSCT. Figure 1. Correlation of Liver iron content with Ferritin. Figure 1. Correlation of Liver iron content with Ferritin. Disclosures: No relevant conflicts of interest to declare.

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