Liver Iron Concentration In Patients Research Articles

Influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome: A retrospective study

目的分析骨髓增生异常综合征（MDS）患者铁代谢评估的影响因素。方法181例MDS患者接受磁共振成像（MRI）和（或）能谱CT（DECT）对肝脏和心脏铁浓度的检测，其中41例患者在2次检查期间接受了规律铁螯合治疗（ICT）。同步检测调整铁蛋白（ASF）、红细胞生成素（EPO）、心功能、肝转氨酶、肝炎抗体、外周血T细胞极化等指标，并收集患者是否合并骨髓纤维化、脾大、环孢素A使用等信息进行比较分析。结果MRI组、DECT组肝铁浓度均与ASF呈正相关（r分别为0.512、0.606，P值均<0.001），MRI组心铁浓度与ASF仅呈弱相关（r＝0.303，P<0.001），而DECT组心铁浓度与ASF无明显相关性（r＝0.231，P＝0.053）。输血依赖显著影响患者肝和心铁浓度［MRI组：LIC：（28.370±10.706）mg/g对（7.593±3.508）mg/g，t＝24.30，P<0.001；MIC：1.81对0.95，z＝2.625，P<0.05，DECT组：肝VIC：（4.269±1.258）g/L对（1.078±0.383）g/L，t＝23.14，P<0.001：心VIC：1.69对0.68，z＝3.142，P<0.05］。重度以上铁过载组患者EPO浓度明显高于轻中度铁过载组及正常组（P值均<0.001）；MDS伴环状铁粒幼红细胞（MDS-RS）患者与和其他MDS低危组患者相比，肝铁浓度明显增高［DECT组：3.80（1.97,5.51）g/L对1.66（0.67,2.94）g/L，P＝0.004；MRI组：13.7（8.1,29.1）mg/g对11.6（7.1,21.1）mg/g，P＝0.032］。而年龄、骨髓纤维化、脾大、T细胞极化、环孢素A的使用、肝转氨酶、肝炎抗体阳性等因素对铁代谢无明显影响。结论MDS患者肝铁浓度与ASF呈正相关，心铁浓度与ASF无明显相关性。输血依赖、EPO浓度、合并RS是铁代谢的影响因素。

The serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia: is there a good correlation?

ABSTRACT Introduction Liver iron overload is common in patients with thalassemia. In patients with beta-thalassemia, the correlation between serum ferritin and liver iron concentration is well established. The correlation between serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia remains limited. Methods This is a cross-sectional study in patients with alpha-thalassemia aged ≥ 18 years old at Srinagarind Hospital, Khon Kaen University, Thailand. Liver iron concentration (LIC) was evaluated by the MRI-T2* technique. Linear logistic regression analysis was used to determine the correlation between serum ferritin levels and liver iron concentrations. Results One hundred and thirty-one of the MRI-T2* measurements from 65 patients with alpha-thalassemia were evaluated. Patients with non-deletional alpha-thalassemia had higher LIC compared to patients with deletional alpha-thalassemia. The serum ferritin levels were relatively low at the same levels of LIC in patients with non-deletional alpha-thalassemia compared to deletional alpha-thalassemia. Conclusions The correlation of serum ferritin levels and LIC was modest and different among alpha-thalassemia genotypes. A different serum ferritin threshold is needed to guide iron chelation therapy in patients with alpha-thalassemia. Evaluation of liver iron concentration is necessary for patients with alpha-thalassemia, especially in patients with non-deletional alpha-thalassemia.

Long-Term Efficacy and Safety of Betibeglogene Autotemcel Gene Therapy for the Treatment of Transfusion-Dependent β-Thalassemia: Results in Patients with up to 6 Years of Follow-up

Long-Term Efficacy and Safety of Betibeglogene Autotemcel Gene Therapy for the Treatment of Transfusion-Dependent β-Thalassemia: Results in Patients with up to 6 Years of Follow-up

Liver iron concentration in dysmetabolic hyperferritinemia: Results from a prospective cohort of 276 patients

Introduction and objectivesWe aimed to study the liver iron concentration in patients referred for hyperferritinemia to six hospitals in the Basque Country and to determine if there were differences between patients with or without metabolic syndrome. Patients and methodsMetabolic syndrome was defined by accepted criteria. Liver iron concentration was determined by magnetic resonance imaging. ResultsWe obtained the data needed to diagnose metabolic syndrome in 276 patients; a total of 135 patients (49%), 115/240 men (48%), and 20/36 women (55.6%) presented metabolic syndrome. In all 276 patients, an MRI for the determination of liver iron concentration (mean±SD) was performed. The mean liver iron concentration was 30.83±19.38 for women with metabolic syndrome, 38.84±25.50 for men with metabolic syndrome, and 37.66±24.79 (CI 95%; 33.44–41.88) for the whole metabolic syndrome group. In 141 patients (51%), metabolic syndrome was not diagnosed: 125/240 were men (52%) and 16/36 were women (44.4%). The mean liver iron concentration was 34.88±16.18 for women without metabolic syndrome, 44.48±38.16 for men without metabolic syndrome, and 43.39±36.43 (CI 95%, 37.32–49.46) for the whole non-metabolic syndrome group. Comparison of the mean liver iron concentration from both groups (metabolic syndrome vs non-metabolic syndrome) revealed no significant differences (p=0.12). ConclusionsPatients with hyperferritinemia and metabolic syndrome presented a mildly increased mean liver iron concentration that was not significantly different to that of patients with hyperferritinemia and non-metabolic syndrome.

Liver iron concentration is not raised in patients with dysmetabolic hyperferritinemia

Background & aims. Hyperferritinemia (HF) is frequently present in patients with metabolic syndrome (MS). MS associated with HF is named dysmetabolic hyperferritinemia (DH). There are some publications that propose that DH is associated with a raised liver iron concentration (LIC). We studied the LIC in patients referred for HF to a secondary hospital to determine if there are differences between patients with or without MS.Material and methods. We conducted a prospective study of 132 consecutive patients with HF from January to December 2010. The MS was defined by the International Diabetes Federation criteria (2005). LIC was determined by Magnetic resonance imaging (MRI).Results. The number of patients for which there was enough data to determine MS was 97, out of which 54 had MS and 43 had no MS (NMS). In 54/97 patients, MRI for LIC determination was performed. From the MS group, 44 were men (27 underwent MRI) and 10 women (9 MRI). The mean LIC was 27.83 ± 20.90 μmol/g for the MS group. In the NMS group, 36 were men (13 MRI), and 7 women (5 MRI). In 18 patients from the NMS group, LIC was determined by MRI. The mean LIC was 33.16 ± 19.61 μmol/g in the NMS group. We compared the mean values of LIC from both groups (MS vs. NMS) and no significant differences were found (p = 0.067).Conclusion. Patients with DH present a mean LIC within normal values and their values do not differ from those of patients with HF but without MS.

Measurement of the liver iron concentration in transfusional iron overload by MRI R2* and by high-transition-temperature superconducting magnetic susceptometry

PurposeTo compare measurement of the liver iron concentration in patients with transfusional iron overload by magnetic resonance imaging (MRI), using R2*, and by magnetic susceptometry, using a new high-transitiontemperature (high-Tc; operating at 77 K, cooled by liquid nitrogen) superconducting magnetic susceptometer. MethodsIn 28 patients with transfusional iron overload, 43 measurements of the liver iron concentration were made by both R2* and high-Tc magnetic susceptometry. ResultsMeasurements of the liver iron concentration by R2* and high-Tc magnetic susceptometry were significantly correlated when comparing all patients (Pearson's r = 0.91, p < 0.0001) and those with results by susceptometry >7 mg Fe/g liver, dry weight (r = 0.93, p = 0.006). In lower ranges of liver iron, no significant correlations between the two methods were found (0 to <3.2 mg Fe/g liver, dry weight: r = 0.2, p = 0.37; 3.2 to 7 mg Fe/g liver, dry weight: r = 0.41; p = 0.14). ConclusionThe lack of linear correlation between R2* and magnetic susceptibility measurements of the liver iron concentration with minimal or modest iron overload may be due to the effects of fibrosis and other cellular pathology that interfere with R2* but do not appreciably alter magnetic susceptibility.

Liver Iron Concentration in Patients Referred to a Secondary Hospital for Hyperferritinemia: Analysis of the Different Groups According to HFE Mutations and the Transferrin Saturation Index

Background: Olynyk et al. studied the liver iron concentration (LIC) by MRI of 52 consecutive patients of northern European origin who were referred to a tertiary hospital for hyperferritinemia (HF). They described three groups according to HFE mutations and the transferrin saturation index (TSI) (group A: no predisposing mutations (PM) for hereditary hemochromatosis (HH) and TSI > 45 %, group B: PM for HH and TSI > 45 %; group C: no PM for HH and normal TSI). In the Basque country, HH predisposing mutations differ, with prevalence of the H63D/H63D mutation. Objectives: To study the importance of HFE mutations and the TSI in determining LIC of HF patients attending the outpatient clinic at a secondary hospital. Methods: Prospective study of 132 consecutive patients with HF. In 120 HFE study was available. In 79 LIC was obtained by MRI. In 71 patients values of HFE mutations, TSI, and LIC by MRI were available. Results: Mean age: 55.68 ± 14.26 (23 - 83), 55 men and 16 women. The mean LIC in men was 35.66 ± 36.85; women 38.81 ± 29.75. The mean LIC in group A: 38.80 ± 45.18 (5 - 210), group B: 48.96 ± 37.51 (15 - 160), group C: 28.12 ± 18.85 (5 - 75). We compared the LIC mean values of the 3 groups with no significant differences. Conclusions: LIC values are similar in different groups of patients referred to a secondary hospital for HF, despite variable predisposition to HH.

THU-393 - Liver iron concentration in patients referred for hyperferritinemia: multicenter analysis of the different groups according to HFE mutations and transferrin saturation index, prediction of liver iron overload in Southern Europe

THU-393 - Liver iron concentration in patients referred for hyperferritinemia: multicenter analysis of the different groups according to HFE mutations and transferrin saturation index, prediction of liver iron overload in Southern Europe

Iron Overload Status in Patients with Non-Transfusion-Dependent Thalassemia in China

▪Background: Non-transfusion-dependent thalassemia (NTDT) is a genetic disorder most commonly including beta-thalassemia intermedia (Beta-TI), HbE/Beta thalassemia (HbE/Beta thalassemia), and hemoglobin H disease (HbH disease). NTDT patients can be at risk of iron overload due to increased intestinal iron absorption triggered by chronic anemia, ineffective erythropoiesis and, possibly, decreased serum hepcidin. Despite NTDT is popular in southern China, there is little data evaluating iron overload in Chinese patients. This study aimed at investigating the occurrence, prevalence and severity of iron overload in Chinese population with NTDT.Methods: We evaluated the serum ferritin (SF), liver iron concentration (LIC) and cardiac T2* in 158 NTDT patients (83 with HbH disease, 45 with Beta-TI and 30 with HbE/Beta thalassemia) in China. The median age was 22 years old. The main characteristics of these patients along with the main results of the study were summarized in Table 1. Blood samples were obtained for the assessment of hemoglobin (Hb) and serum ferritin (SF) levels. LIC was assessed by using validated R2 magnetic resonance imaging [MRI] (FerriScan®). Cardiac iron level was measured by MRI T2*. Patients were scanned with MRI 1.5 T (Siemens Avanto, Germany). The study was performed at the First Affiliated Hospital of Guangxi Medical University. LIC < 3mg Fe/g dw and cardiac T2* > 20ms was considered normal. Abnormal LIC can be divided into mild: 3-7mg Fe/g dw, moderate: 7-15mg Fe/g dw, severe: >15mg Fe/g dw. All patients or parents/guardians provided their written informed consent to participate in this study. The study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University.Results: The median SF level of 158 NTDT patients was 1,037(27.0-19,704) ng/ ml. LIC was detected in 155 patients (98.1%) and the median LIC value was 8.9(0.6-43) mg Fe/g dw. There were 15 patients (60%) (8 with HbH disease, 5 with Beta-TI and 2 with HbE/Beta thalassemia)<10 years old found liver iron overload. The youngest patient with liver iron overload was 5 years old with 5.6mg Fe/g dw in LIC. Cardiac T2*was assessed in 111 patients (70.2%) and the median cardiac T2* was 32.8(7.5-75.1)ms. The 7 patients (4.4%) (4 with HbH disease and 3 with Beta-TI) had cardiac T2*=<20ms. There was a significant correlation between LIC and SF (r=0.809, p<0.001). No correlation between LIC and Hb, cardiac T2* values can be verified.There was a significant correlation between LIC and age (r=0.497, p<0.001)(Fig 1). The levels of LIC in patients > 30-year old group are significantly higher than those in other groups (Fig 2).The patients with Beta-TI and HbE/Beta thalassemia showed a statistically significant lower Hb and higher values of SF and LIC than those of HbH disease patients.Conclusions: Chinese NTDT patients have a high prevalence of iron overload. The iron overload in patients with Beta-TI and HbE/Beta thalassemia are more serious than those in HbH disease patients. The age of patient is a risk factor of iron overload in NTDT patient. Patients > 30 years old have a high burden of iron overload. Our data shows that the first assessment of MRI LIC should be performed as early as 5 years old. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Serum Ferritin Levels Correlation With Heart and Liver MRI and LIC in Patients With Transfusion-Dependent Thalassemia.

Background:Iron-loaded cardiac complication is the essential cause of mortality in patients with thalassemia. Early detection and treatment of cardiac over-load can reduce mortality.Objectives:The current study aimed to evaluate the relationship between serum ferritin levels and T2* magnetic resonance imaging (MRI) of heart and liver and liver iron concentration (LIC) to diagnose iron over load in countries with limited access.Patients and Methods:In the current cross-sectional study, 85 Iranian patients with thalassemia with the mean age of 22.7 ± 7 years were randomly selected. All patients were on regular blood transfusion. Echocardiography of heart and liver T2* MRI, determination of serum ferritin levels, and LIC were performed in all subjects at the same time. The correlation of serum ferritin levels with T2*MRI of heart and liver, and LIC was assessed. P value < 0.05 was considered statistically significant.Results:Abnormal myocardial iron load (T2* MRI < 20 ms) was detected in 58% of the patients and among whom, 36% had severe myocardial iron load (T2* MRI < 10 ms). Median and interquartile range of serum ferritin levels were 1434 and 2702 respectively in patients with thalassemia. Serum ferritin levels showed a statistically significant positive correlation with LIC (rs = 0.718, P < 0.001) and significant negative correlation with T2* Heart (rs = -0.329, P = 0.002), and T2* Liver (rs = -0.698, P < 0.001). However, Ejection fraction was not significantly correlated with serum ferritin levels in the patients (P = 0.399).Conclusions:Serum ferritin levels can be used to diagnose iron over-load in patients with thalassemiaas an alternative method in areas where T2* MRI is not available.

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

▪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 1Liver iron concentration determined by Ferriscan (R2) in patients with hemoglobinopathies treated by different chelation regimens.TMTIS/ b -TChelation TherapyLIC R2 (mean±sd)LIC R2 (mean±sd)LIC R2 (mean±sd)DFO5.3±5.78.5±7.720.9±19.9DFP12.9±12.312.5±8.112.7±20.2DFX7.6±9.26.1±7.13.7±3.2Combined DFO+DFP10.1±12.117.8 (n=1)---Sequential DFO-DFP4.3±3.1------Combined DFO+DFX---9.7 (n=1)--- [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

In-Accuracy Of Bone Density Measurements By DXA In Patients With Hemoglobinopathies and Iron Overload

IntroductionWhen monitoring bone health in patients with hemoglobinapathies, it is unknown if iron in surrounding tissues can lead to inaccuracies in the 2-dimensional assessment by Dual Energy X-ray Absorptiometry (DXA). ObjectiveThe aims of this study were: 1) to determine if the accuracy of lumbar spine assessment by DXA is affected by high liver iron concentration in patients with Sickle Cell Disease (SCD) or Thalassemia (Thal), 2) to test the effect of high tissue iron on vertebral Z-scores using phantoms, 3) to explore the ability to account for potential high-iron content effects when performing DXA examinations. MethodsThis study consisted of a retrospective chart review of data collected by the Children's Hospital & Research Center Oakland, Bone Density Clinic and Iron Measurement Program. Data from both DXA and Super Conducting Quantum Interference Device (SQUID) examinations collected between 2002 and 2013 from were abstracted. Only those patients with a diagnosis of SCD or Thal, who had a DXA and SQUID measurement within the same year were divided into an iron overload group (liver iron concentration (LIC) >3,000 µg Fe/g wet) and low iron (LIC <500 µg Fe/g wet) group. These patients were compared with healthy controls of which only 13 had both DXA and SQUID tests, 34 had DXA only. The 34 healthy controls without a SQUID test were included because it was assumed, based on their health screen that their liver-iron content would not interfere with DXA. In order to explore aim 1, a lumbar spine scan, by DXA, of each subject was re-analyzed to compare the derived areal bone mineral density (aBMD) Z-scores of lumbar vertebrae that are covered by the liver (presumed L1 or L1/L2) with the Z-scores of the lumbar vertebrae not covered by the liver (L3/L4). To explore aim 2, phantoms were designed to mimic the geometry of iron loaded tissues in order to explore the contribution of iron in specific tissues on the accuracy of DXA assessments. Phantoms were constructed using KNOX® brand gelatin and iron(II) sulfate heptahydrate and had concentrations ranging from 3,000 to 7,000 ug Fe/g gelatin. The iron-loaded phantoms were positioned obtusely overlying L1/L2 of the DXA daily quality control phantom to mimic the position of the liver. All data were analyzed by STATA ver.9.2 and were considered significant with a p<0.05. ResultsData from 102 total visits abstracted from 88 subjects [19 SCD (13 F), 24 Thal (12 F), age: 30.1 ± 11.9 years, mean ± SD], and 45 healthy controls (24 F, age: 25.4 ± 11.0 yrs) were analyzed. The SCD and Thal group had an average LIC by SQUID of 4651 ± 2079 µg Fe/g wet tissue and serum ferritin of 5408±2706 ng/mL; while the healthy controls, with both a DXA and a SQUID (n=17), had an average LIC of 251±144. Average aBMD Z-score of the lumbar spine L1-L4 in the Thal group was -2.0 ± 1.1 , the SCD was -2.0 ± 1.6 and the healthy controls: -0.3 ± 0.9. However, when individual vertebrae are analyzed separately, a significant difference was observed between the lumbar spine L1 BMD Z-scores compared to the combined means of L3/L4 Z-scores in the iron loaded population (Table 1). The discrepancy was even greater in subjects with LIC >5000 ug/g wet tissue. These findings were reproduced using heavily iron loaded phantoms.Table1Summary of Vertebrae Analysis by DXA in Controls, Patients and PhantomsSubject groupL1 aBMD Z-ScoreAvgL3/L4 aBMD Z-scoreMean difference L1 vs AvgL3/L4Difference (L1 vs AvgL3/L4)p-valueControls (n=52)-0.29 ± 0.16-0.50 ± 0.170.21 ± 0.08-0.42 ± 0.12<0.001SCD & Thal (n=50)-1.60 ± 0.18-2.21 ± 0.180.63 ± 0.09Controls (n=52)-0.29 ± 0.16-0.50 ± 0.170.21 ± 0.080.70 ± 0.16<0.001LIC >5000 (n=18)-1.43 ± 0.28-2.35 ± 0.260.91 ± 0.15Control Phantom (n=10)0.76 ± 0.08-0.17 ± 0.070.93 ± 0.03-1.0 ± 0.16< 0.001Iron Phantom (n=10)1.70 ± 0.47-0.22 ± 0.101.92 ± 0.15 ConclusionsInitial results for this study show that there is a relationship between liver iron content and lumbar spine aBMD Z-scores when evaluated by DXA. The BMD Z-score for L1 appears to be more significantly affected by the liver iron content then L2, which was unanticipated. When evaluating patients with liver iron content >3,000 ug/g wet tissue, it is important to consider the effects of iron contribution from the liver on the DXA spine scans and delete L1 and/or L2 from the total Z-score prior to making an interpretation. Failing to do so may under diagnose low bone mass in this at risk patient population. Disclosures:No relevant conflicts of interest to declare.

Correlation study between MR quantitative cardiac iron accumulated and serum ferritin, liver iron concentration in patients with .BETA.-thalassemia major

Objective Using MRI-T2 * method to quantify the cardiac iron overload in patients with β-thalassemia major and to evaluate the correlation between cardiac T2 * values and serum ferritin (SF),liver iron concentration(LIC).Methods Fifty-eight over 10 years old transfusion-dependent patients with β-thalassemia major were underwent MRI heart measurement to obtain T2 * values.Spearman rank correlation was used to analyze the relationship between cardiac T2*,SF,and LIC.Patients were divided into two groups based on standard setting (SF ＞2500 μg/L or LIC ＞ 15 mg/g of dry tissue).Differences of cardiac T2 * values between two groups were evaluated by Wilcoxon rank sum test with cardiac T2 * ＜ 20 ms as diagnosis standard.The sensibilities and specificities of prediction for cardiac iron deposition with the index of SF ＞ 2500 μg/L or LIC ＞ 15 mg/g dry tissue were calculated,and receiver operating characteristic (ROC) curve analysis was performed.Results The range (median) of cardiac T2 * values,SF and LIC in 58 patients were 4.7-51.1 ms (14.0 ms),1345-23 640 μg/L (5741 μg/L),9.0-＞43.0 mg/g dry tissue (41.4 mg/g),respectively.There was no linear correlation between cardiac T2 * values and SF (r =-0.240,P =0.070).Cardiac T2 * values and LIC was weakly correlated (r =-0.420,P =0.002).The range (median) of cardiac T2 * values was 6.1-47.6 ms (23.7 ms) in 7 patients of SF ≤ 2500 μg/L group.The range (median) of cardiac T2 * values was 4.7-51.1 ms(13.5 ms) in 51 patients of SF ＞2500 μg/L group.There was no statistically significant difference between two groups (Z =-0.489,P =0.625).The range (median) of cardiac T2 * values was 24.4-51.1 ms (44.8 ms) in 5 patients of the LIC ≤15 mg/g dry tissue group.The range (median) of cardiac T2 * values was 4.7-45.5 ms (13.2 ms) in 53 patients of HIC ＞ 15 mg/g dry tissue group.There was significant difference between T2 * values of the two groups(Z =-2.895,P =0.004).To predict cardiac iron deposition,the sensibilities and specificities were 90.9％ (30/33) and 16.0％ (4/25) for the index of SF ＞2500 μg/L,100.0％ (33/33) and 20.0％(5/25) for LIC ＞ 15 mg/g dry tissue respectively.The areas under the ROC curve were 0.652 with the index of SF and 0.775 with the index of LIC.Conclusions MRI-T2 * method can directly quantify the cardiac iron overload in patients with β-thalassemia major.There is no linear correlation between cardiac T2 * values and SF.Cardiac T2 * values and LIC is weakly correlated.Using SF or LIC as an indirect index to predict cardiac iron deposition is not reliable in clinical. Key words: Thalassemia; Iron metabolism disorders; Magnetic resonance imaging; Heart

Rates of Non-Transfusional Iron Accumulation (NTIA) In Hemoglobin E Thalassemia

Abstract 5147 In patients with Hemoglobin (Hb) E thalassemia, the most common form of severe thalassemia worldwide (Weatherall DJ. Blood 2010;4331-6), early reports suggest that this disorder is associated with variable iron loading in the absence of frequent transfusions (Olivieri NF et al. Int J Ped Hem Onc 2000; 22:593-7), possibly related to the phenotypic variability of the disorder. At the National Thalassaemia Centre, Kurunegala, Sri Lanka, we have studied two groups of patients with Hb E thalassemia using spin density projection assisted R2-MRI (R2-MRI; FerriScan) (St Pierre TG et al. Blood 2005; 105:855-61). Group 1 (n=23) had received ≤ 20 transfusions (median = 9) lifelong, despite a relatively advanced age (mean ± SD, 27.5 ± 16.2 [range 7.8–57.4] years). Group 2 (n=47) had received > 20 transfusions lifelong. In Group 1, liver iron concentration (LIC) was strikingly variable (geometric mean 5.6 [range 1.0–33.0] mg Fe/g dw). LIC exceeded 7 mg Fe/g dw in 11 patients and 15 mg Fe/g dw in 4 patients. Values of serum ferritin (SF) (mean ± SD, 827 ± 611 [range 254–2484] ug/L) and serum ALT (37.6 ± 19.7 [range 12–86] U/L) did not reliably reflect the degree of elevation in LIC (R2 = 0.38, P = 0.0017 for SF; R2 = 0.12, P = 0.10 for ALT). These elevations of body iron burden were associated with evidence of organ dysfunction, with abnormal ALT (observed in 11 patients), hypothyroidism (6 patients), final adult height Rates of change of LIC in patients receiving Disclosures: St. Pierre:Resonance Health Ltd: Consultancy, Equity Ownership, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis Pharmaceuticals Inc: Consultancy, Research Funding, Speakers Bureau.

Iron chelation therapy for patients with sickle cell disease and iron overload

A 21-year-old male with sickle cell disease (SCD) presented with severe pallor. He had received a total of 100 red blood cell (RBC) units in his lifetime, had a mean serum ferritin level of 3133 ng/ml, and liver iron concentration (LIC) of 12 mg Fe/g dry weight (dw). He was started on subcutaneous deferoxamine (DFO) infusions at a dose of 56 mg/kg/d, five days a week (equivalent to 40 mg/kg/d, seven days a week) and continued to receive 8–10 RBC units/year as treatment for pain. During the first six months of chelation therapy, his serum ferritin levels fell by around 50% of the pretreatment value, but then started to increase back up to the baseline values. The patient was noncompliant with DFO therapy. He experienced pain at the site of injection, could not sleep and was concerned about carrying a pump and not being accepted by his peers. He dropped out of college and abstained from all social activities. He was referred to a psychologist; however, this failed to improve compliance and he opted to stop DFO therapy altogether.

Correlation of Serum Ferritin Levels and Liver Iron Concentration Determined by R2* MRI in Patients with Thalassemia Intermedia.

Background: Unlike patients with thalassemia major (TM), those with thalassemia intermedia (TI) do not require regular blood transfusion therapy but remain susceptible to iron overload due to increased intestinal iron uptake triggered by ineffective erythropoiesis. TI patients can accumulate 1–3.5 g of excess iron per year, and effective monitoring of iron burden is an important element of patient management. Assessment of serum ferritin (SF) levels is a convenient and widely used method, and a correlation between SF and liver iron concentration (LIC) has been demonstrated in patients with TM. SF levels may, however, be a poor indicator of LIC in patients with TI and the limited data available on the SF:LIC correlation prove equivocal; in fact, reports suggest a discrepancy between LIC and SF in patients with TI. This is the largest study to use R2* MRI to evaluate the SF:LIC correlation in patients with TI.Methods: This was a cross-sectional study of randomly selected, infrequently/non-transfused TI patients treated at a chronic care center in Hazmieh, Lebanon. Patient charts were reviewed and a medical history was compiled. Blood samples were taken for SF assessment, and LIC was determined by R2* MRI.Results: Data from 74 TI patients were included in this analysis (33 male, 41 female; mean age 26.5 ± 11.5 years). Of this group, 59 (79.7%) patients were splenectomized, 20 were transfusion-naive, 45 had received several transfusions in their lifetime but none in the past year, and 9 patients were regularly transfused 2–4 times per year. Overall mean SF values were 1023 ± 780 ng/mL (range 15–4140); mean LIC levels were 9.0 ± 7.4 mg Fe/g dry weight [dw] (range 0.5–32.1). In contrast to previous findings, a significant positive correlation between mean LIC and SF values was seen in the whole group (R=0.64; P<0.001), and in a subset of splenectomized patients (R=0.62; P<0.001). In comparison with data obtained from a randomly selected group of patients with TM treated at the center, SF levels in TI were seen to be significantly lower, while the mean LIC values were similar in both groups of TI and TM. For a given LIC, SF values were lower in patients with TI than those with TM (Figure).Conclusions: Evaluation of iron levels shows that many patients with TI have SF and LIC levels above the recommended threshold levels, indicating a risk of significant morbidity/mortality. Similar to TM, a significant correlation between SF and LIC was observed in patients with TI; however, the relationship between SF and LIC was different between TI and TM (for the same LIC, the SF values in TI were lower than those in TM). Therefore, use of the current threshold for iron overload based on SF values in TM will lead to significant underestimation of the severity of iron overload in patients with TI. This may result in delayed chelation therapy, and expose patients to morbidity and mortality risks associated with iron overload. Disease-specific management approaches are therefore required in patients with TI. This includes either regular assessments of LIC, ideally by non-invasive R2* MRI, or lowering the SF threshold for initiating iron chelation in patients with TI. [Display omitted]

Serum Ferritin and Liver Iron Concentration in Patients with Iron Overload.

Despite its limitations, serum ferritin (SF) is commonly used to monitor chelation therapy in primary and secondary hemochromatosis. To better predict liver iron concentration (LIC), we prospectively investigated the relationship between SF and LIC in a total of 421 patients with primary (HFE-1 associated, n=241) or secondary hemochromatosis (n=180), consisting of chronically transfused thalassemia (Tx-Thal: n=89) or sickle cell disease patients (Tx-SCD: n=45) and transfusion independent thalassemia patients (nTx-Thal: n=26). In all patients, LIC was measured by SQUID biosusceptometry. SF correlated with LIC (RS = 0.51–0.83, p < 0.001) but was a poor predictor for LIC. SF was significantly lower (p < 0.001) in nTx-Thal and HFE-1 patients despite similar LIC (421 – 5524 μg/g-liver) and it was higher in Tx-SCD compared to Tx-Thal (p = 0.03). In order to improve the value of SF, we calculated the SF/LIC ratio for each group. SF/LIC remained stable over time in patients whose therapy did not change. In iron loaded patients without blood transfusion therapy (nTx-Thal and HFE-1), the median SF/LIC ratio was significant lower (0.32 and 0.43) as compared to transfused patients (Tx-Thal: 0.87, HCV-Thal: 0.99, Tx-SCD: 1.2), probably, indicating differences in the secretion of ferritin into plasma. We conclude that SF alone can mislead the iron unloading therapy as it underestimates LIC in nTx-Thal patients and overestimates LIC in Tx-SCD patients. Once the initial LIC value is obtained and the individual SF/LIC ratio is determined in a patient, the ratio together with SF may be more useful than SF alone to monitor iron overload and predict LIC.

Semi-Quantitative Assessment of Hemosiderin Distribution Accurately Reflects Reductions in Liver Iron Concentration Following Therapy with Deferasirox (Exjade®, ICL670) or Deferoxamine in Patients with Transfusion-Dependent Anemia.

Introduction: Direct biochemical measurement of liver iron from biopsy is the reference standard for determining liver iron concentration (LIC) and therefore the efficacy of chelation therapy. Semi-quantitative assessment of liver iron using Prussian blue stained tissue sections has, however, also been shown to correlate with LIC in patients with non-transfusional hemosiderosis.Aim: To determine the value of semi-quantitative liver iron measurement as an indicator of LIC in patients with transfusion-dependent anemia treated with reference standard therapy deferoxamine (DFO) or the investigational once-daily, oral iron chelator deferasirox. The differential involvement of hepatocytes and macrophages in the storage of excess iron was also assessed.Methods: During the deferasirox registration studies, semi-quantitative determination of liver tissue iron score (TIS) was performed in all patients who underwent liver biopsy; these data were compared with other markers of iron overload such as LIC and serum ferritin. In Studies 0107 and 0108, 454 patients with β-thalassemia and 101 patients with β-thalassemia or rare anemias (MDS, DBA and others) underwent liver biopsy at the start of the study and again after 1 year of chelation therapy with deferasirox (Study 0107, n=224 and all patients of 0108) or DFO (Study 0107 only, n=230). Patients analyzed in Study 0108 had β-thalassemia (n=61) or rare anemias (n=40).Results: There was a good correlation between semi-quantitative and quantitative liver iron measurements in all patient populations (R≥0.80, Pearson correlation coefficient). Baseline and change from baseline TIS and LIC are given in Table 1. These changes were dose-dependent, with the greatest decrease observed in patients treated with the highest deferasirox dose (30 mg/kg: TIS decreased from 34.3 ± 7.7 to 25.9 ± 11.2, n=107, in Study 0107; and from 35.3 ± 7.6 to 29.2 ± 10.3, n=78, in Study 0108). Further analyses demonstrated that both deferasirox and DFO were active in removing iron from different functional areas of liver tissue (hepatocytic, sinusoidal and portal areas).Table 1Overall TIS and LIC changes after 1 year of treatmentStudy 0107Study 0108DFODeferasiroxβ-thalassemiaRare anemias(n=230)(n=224)(n=61)(n=40)TIS*- Baseline24.0 ± 10.325.3 ± 11.229.9 ± 10.934.1 ± 9.2- Change from baseline−2.4 ± 11.2−3.5 ± 7.1−4.8 ± 11.2−6.2 ± 10.1LIC, mg Fe/g dw*- Baseline14.5 ± 9.615.7 ± 10.121.2 ± 10.922.8 ± 9.4- Change from baseline−3.0 ± 8.8−3.2 ± 5.7−5.8 ± 9.1−5.5 ± 7.5*Mean ± SDConclusions: Semi-quantitative iron assessment clearly correlates with quantitative iron measurement. The impact of iron chelation therapy on iron deposits was seen in all functional areas of the liver, with the highest decrease observed in patients treated with deferasirox.

Deferasirox a strong contender for iron overload in all ages

Deferasirox [Exjade, ICL 670], an oral once-daily iron chelator, was shown to be effective in the treatment of iron overload in both adults and children in studies presented at the 46th Annual Meeting of the American Society of Hematology (ASH) [San Diego, US; December 2004]. In a phase III study involving almost 600 patients with thalassaemia, deferasirox produced dose-dependent reductions in liver iron concentration (LIC), to levels comparable to those observed with the current standard therapy, deferoxamine. A phase II study showed that deferasirox reduced LIC in patients with myelodysplastic syndromes and Diamond-Blackfan syndrome, and in patients with thalassaemia who had inadequate chelation with deferoxamine.