R* Magnetic Resonance Imaging (MRI) of the Liver for Patients with Iron Overload.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2670-2670
Author(s):  
Jane S. Hankins ◽  
M. Beth McCarville ◽  
Ralph Loeffler ◽  
Ruitian Song ◽  
Russell E. Ware ◽  
...  
Keyword(s):  
Liver Biopsy ◽  
Iron Overload ◽  
Correlation Coefficient ◽  
Serum Ferritin ◽  
Iron Content ◽  
Bone Marrow Failure ◽  
Correlation Coefficients ◽  
Beta Thalassemia ◽  
Liver Iron ◽  
Hematological Diseases

Abstract Iron overload is an inevitable consequence of multiple transfusions and occurs in many hematological diseases including sickle cell anemia (SCA) and beta thalassemia (β-thal). Liver biopsy provides quantification of iron content in the liver, but is not without risks such as bleeding, pain, and infection. MRI R2* has the advantage of quantifying liver iron without the risks of invasive procedures, however, this technique has not been fully investigated or validated. Furthermore, the variability introduced by multiple MRI readers has not been investigated to date. Patients with hematological diseases were selected to participate in this prospective IRB-approved study if they received ≥ 18 transfusions or had a serum ferritin ≥ 1000 ng/mL. All study participants completed 1.5 Tesla MRI R2* testing (Siemens Symphony), serum ferritin, and liver biopsy with quantification of liver iron content (LIC) within 30 days. Regions of interest (ROI) were drawn on R2* maps in a homogeneous area of the right hepatic lobe, avoiding blood vessels and obvious bile ducts. Three independent reviewers, blinded to the patients’ clinical status and the other 2 reviewers’ results, performed the ROI analysis. The correlation between LIC and liver R2* was calculated using the Spearman’s Rank-Order Correlation Coefficient. Due to possible outliers in the data, robust simple linear regression methods were used to fit a regression line to scatter plots. All liver biopsy samples were sent to Mayo Laboratories for LIC quantification. The agreement among the 3 raters was assessed using the interclass correlation coefficient (ICC). Forty-seven patients, median age 14 years (range 7 – 37) participated; 24 were female. Thirty-five of them had SCA, 8 had β-thal (major or intermedia), and 4 had bone marrow failure syndromes. Total table time for R2* MRI testing was between 20 to 30 minutes. All patients tolerated the liver biopsy without complications. The mean (±1SD) ferritin was 2917ng/mL (±2239), mean LIC was 12.139 mg/ 100g of dry weight liver (±8.269), and mean liver R2* ranged from 425 to 432 Hz (±257 to 249 Hz). All 3 raters produced R2* values strongly associated with LIC, with correlation coefficients from 0.93 to 0.95 (p<0.00005). There was a significant positive association between serum ferritin and R2* liver values (correlation among the 3 reviewers ranged from 0.39 to 0.50 with all p<0.009). The agreement among the 3 raters was 0.98. To summarize: 1) 1.5 T MRI R2* liver values are highly associated with LIC in patients with iron overload. This is the largest sample of MRI R2* liver measurements correlated with LIC obtained by liver biopsy; 2) The three raters had excellent agreement which suggests that, in our study, R2* liver values do not differ greatly among qualified readers; 3) R2* measurements of the liver were significantly associated with serum ferritin, however, the correlation coefficients were relatively low (0.39 to 0.50), documenting a weak relationship; and 4) MRI R2* of the liver is a feasible and valid technique to assess LIC non-invasively, and appears to be reproducible when performed by qualified reviewers. We conclude that liver MRI R2* can be incorporated into clinical research protocols for safe, painless, and accurate liver iron quantitation.

Does Gene Therapy in Beta Thalassemia Normalize Novel Markers of Ineffective Erythropoiesis and Iron Homeostasis?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 816-816 ◽  
Author(s):  
Alexis A. Thompson ◽  
Tomas Ganz ◽  
Mary Therese Forsyth ◽  
Elizabeta Nemeth ◽  
Sherif M. Badawy
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Research Funding ◽  
Iron Homeostasis ◽  
Beta Thalassemia ◽  
Ineffective Erythropoiesis ◽  
Liver Iron ◽  
Equity Ownership

BACKGROUND: Ineffective erythropoiesis in thalassemia alters iron homeostasis, predisposing to systemic iron overload. Successful allogeneic hematopoietic stem cell transplantation (HSCT) in thalassemia major corrects anemia, should eliminate ineffective erythropoiesis (IE) and normalize iron homeostasis (IH). Whether gene therapy (GT) will fully correct IE and IH is not known. This cross-sectional observational study evaluated the iron status of patients with beta thalassemia following HSCT or GT, and compared them with cohorts of patients with thalassemia intermedia (TI) or transfusion-dependent thalassemia (TDT) using recently introduced biomarkers along with imaging studies and other clinical assessments to better understand and characterize IE and IH across groups. METHODS: We evaluated a convenience sample of 29 participants with beta thalassemia (median age 25 years, IQR 21-35; females 55%; Asian 52%). Participants in the HSCT (n=6) and GT (n=10) groups were evaluated on average 116.5 and 46.9 months following cell infusion, respectively. TDT patients (n= 9) were evaluated pre-transfusion and off iron chelation for at least 7 days, and TI (n=4) were un-transfused or not transfused in >3 years. Clinical lab assessments and MRI R2*/ T2* to assess heart and liver iron burden including post-processing, were performed using local clinical protocols. ELISAs for hepcidin, erythroferrone (Erfe) and GDF-15 were performed in a blinded manner. RESULTS: Median values for all IE and IH parameters tested were normal in the HSCT group, and were significantly lower than in all other groups. There were significant differences among all groups for hemoglobin (p=0.003), erythropoietin (Epo) (p=0.03), serum ferritin (SF) (p=0.01), transferrin (p=0.006), soluble transferrin receptor (sTfR) (p=0.02), serum hepcidin: serum ferritin (H:F) ratio (p=0.006), Erfe (p=0.001), GDF15 (p=0.003), and liver iron content (LIC) by MRI R2* (p=0.02). H:F ratio, a surrogate for predisposition to systemic iron loading, inversely correlated with Erfe (rs= -0.85, p<0.0001), GDF15 (rs= -0.69, p=0.0001) and liver R2* (rs= -0.66, p=0.0004). In a multivariate analysis, adjusted for gender and race, H:F ratio and Epo levels predicted Erfe and GDF15 (p=0.05 and p=0.06; p=0.01 and p=0.05), respectively. Even after excluding GT patients that are not transfusion independent (N=2), SF, Epo, sTfR and hepcidin remain abnormal in the GT group, and there were no significant differences in these parameters between GT and TDT. However, novel biomarkers of IH and IE suggested lower ineffective erythropoiesis in GT compared to TDT (median (IQR) Erfe, 12 (11.6-25.2) vs. 39.6 (24.5-54.7), p=0.03; GDF15, 1909.9 (1389-4431) vs. 8906 (4421-12331), p=0.02), respectively. Erfe and GDF15 were also lower in GT compared to TI, however these differences did not reach statistical significance. There were no differences in hepcidin, ferritin, or H:F by race, however Erfe and GDF15 were significantly lower in Asians compared to non-Asians (p=0.006 and p=0.02, respectively). CONCLUSION: Nearly 4 years post infusion, most subjects with TDT treated with GT are transfusion independent with near normal hemoglobin, however, studies in this limited cohort using conventional measures suggest IE and IH improve, particularly when transfusion support is no longer needed, however they remain abnormal compared to HSCT recipients, who using these parameters appear to be cured. STfR did not detect differences, however GDF15 and Erfe were more sensitive assays that could demonstrate significant improvement in IE and IH with GT compared to TDT. Contribution to IE by uncorrected stem cell populations post GT cannot be determined. Transduction enhancement and other recent improvements to GT may yield different results. Longitudinal studies are needed to determine if thalassemia patients treated with GT will have ongoing IE predisposing to systemic iron overload. Disclosures Thompson: bluebird bio, Inc.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Baxalta: Research Funding. Ganz:Intrinsic LifeSciences: Consultancy, Equity Ownership. Nemeth:Intrinsic LifeSciences: Consultancy, Equity Ownership; Silarus Therapeutics: Consultancy, Equity Ownership; Keryx: Consultancy; Ionis Pharmaceuticals: Consultancy; La Jolla Pharma: Consultancy; Protagonist: Consultancy.

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 ◽  
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.

Serum Ferritin Predicts Liver but Not Cardiac Iron Burden by Noninvasive MRI in Sickle Cell Disease (SCD.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1421-1421 ◽  
Author(s):  
Robert I. Liem ◽  
Cynthia Rigsby ◽  
Richard J. Labotka ◽  
Andrew DeFreitas ◽  
Alexis A. Thompson
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Content ◽  
Iron Loading ◽  
Cell Disease ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Liver Iron Content ◽  
The Mean

Abstract BACKGROUND: Assumptions about iron loading as well as the utility of ferritin to predict transfusional iron overload among individuals with sickle cell disease (SCD) are largely based on extrapolation from data generated in patients with thalassemia major (TM). Yet recent studies suggest the natural history of iron overload in patients with SCD differs significantly from chronically transfused patients with TM. We sought to evaluate the extent of myocardial and hepatic siderosis using noninvasive imaging in chronically transfused patients with SCD and examine its clinical associations, including relationship to long-term trends in serum ferritin, transfusion history, chelation status and markers of hemolysis and inflammation. METHODS: We evaluated 17 subjects (mean age 15±3.6 yrs, range 9 to 20). The mean transfusion duration was 7.3±3.6 yrs (range 2 to 15). Thirteen (76%) patients were on chelation with deferasirox at the time of screening; 4 were not on chelation Rx. MRI T2*/R2* of the heart and liver using a multiple gradient echo sequence was performed on a single 1.5T GE scanner. Hepatic iron concentration (HIC) values were predicted from liver R2* values. RESULTS: Mean HIC in subjects was 9.9±6.7 mg/gm liver dry weight (range 2.5 to 20.8) and was ≥15 mg/gm in 6/17 (35%) subjects. The mean long-term serum ferritin (past 5 yrs, or duration of transfusion if &lt; 5yrs) was 2318±1122 ng/mL (range 541 to 4225). Using Pearson’s correlation coefficient, we observed a significant relationship between HIC and ferritin (r=0.765, p=&lt;0.001). We generated a receiver operator characteristic (ROC) curve to assess the utility of ferritin as a predictor of elevated HIC, using a threshold HIC thought to predict serious iron-related complications. A ferritin cut-off value ≥2164 ng/mL correctly identified 80% of cases of HIC ≥15 mg/gm (AUC 0.96, p=0.003) in our subjects with 83% sensitivity and 73% specificity. Despite markedly elevated HIC and ferritin values in some subjects, none had myocardial siderosis. All 17 subjects had cardiac MRI T2* values in the normal range &gt; 25 ms. Cardiac iron load measured by T2* did not correlate with HIC or serum ferritin. We examined C-reactive protein (CRP) and B-type natriuretic peptide (BNP) as markers for inflammation and myocardial strain, respectively, in our subjects but neither demonstrated a significant relationship to ferritin or MRI findings. BNP, however, did correlate modestly with both age (r=−0.574, p=0.013) and left ventricular ejection fraction on cardiac MRI (r=0.510, p=0.036). A subset of subjects (n=8) had histologic iron measurements by percutaneous liver biopsy (LBx) within 6 months of MRI. While liver iron content by LBx correlated significantly with HIC by MRI (r=0.759, p=0.03), liver iron content by LBx did not correlate with ferritin (r=0.312, p=0.452). CONCLUSION: We found that serum ferritin is a good predictor of liver iron by MRI R2*, and that long term ferritin values ≥2164 ng/mL predict significant hepatic iron overload as assessed by this noninvasive method. We did not observe appreciable cardiac iron loading in our subjects with SCD, which otherwise might have been predicted by elevated HIC alone, as in individuals with TM. These data suggest that reliable, long term surveillance of transfusion-induced iron overload in SCD may be achieved using serum ferritin and HIC by MRI R2* as surrogate markers of hepatic siderosis rather than relying on liver iron content measured invasively by LBx. Also, previously determined thresholds for significant cardiac iron loading in TM, based on degree of hepatic siderosis, may not be applicable in SCD. Further investigation into alternative mechanisms of iron loading or distribution in these related but distinct disorders is warranted.

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

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1287-1287
Author(s):  
Rong rong Liu ◽  
Yu mei Huang ◽  
Peng Peng ◽  
Xiao yun Wei ◽  
Yu Lei ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Genetic Disorder ◽  
Chinese Patients ◽  
Beta Thalassemia ◽  
Iron Level ◽  
Liver Iron ◽  
Liver Iron Overload ◽  
Medical University ◽  
Hbh Disease

Abstract 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. Disclosures No relevant conflicts of interest to declare.

Efficacy and Side Effects of Deferiprone in Children with Iron Overload.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3771-3771
Author(s):  
Rajeswari Thiagarajan ◽  
Phillip Darbyshire ◽  
Sarah Lawson
Keyword(s):  
Side Effects ◽  
Liver Biopsy ◽  
Iron Overload ◽  
Iron Content ◽  
The Other ◽  
Rank Test ◽  
Liver Iron ◽  
Liver Iron Content ◽  
One Year

Abstract Background: Complications due to tissue iron overload are the major cause of morbidity and mortality in patients on long-term transfusion. Desferrioxamine was the only available chelator for treatment until 1999, when Deferiprone (L1) was licensed for use. L1 is an orally active drug unlike desferrioxamine, which can only be used either intravenously or subcutaneously. Aim: The aim of this study was to assess the efficacy and safety of this drug for treatment of children with iron overload. Method: Retrospective analysis of case notes of children on L1 for at least one year duration. Children were on long-term transfusion for transfusion dependent anaemias including thalassaemia major, thalassaemia intermedia and sickle cell anaemia. The main indication for starting L1 was inefficient control of iron overload despite subcutaneous desferrioxamine. L1 was started at a dose of 75 mg/kg bodyweight. Liver biopsy was performed to assess histology and liver iron content prior to starting L1. All patients underwent echocardiogram to assess cardiac status prior to starting L1. The average ferritin levels were recorded for the year before and the year after starting L1. Results: 13 patients met the inclusion criteria. The median age for commencing transfusion was 1.96 years (range 0.16 – 10.83). Desferrioxamine was started a median of 1.25 years after starting transfusion and patients were on desferrioxamine for a median duration of 9 years (range 1.16 – 14.58) before starting L1. 11 patients had liver biopsy prior to starting L1 and 3 had liver biopsy post L1. Wilcoxon Signed Rank Test was used for statistical analysis. The results are tabulated as follows: Pre L1 Post L1 p value Mean Ferritin (microgm/lt) 2359 (1275–4157) 1801 (644–3103) 0.002 Mean Desferal dose/week 10.2 gm 6.78 gm 0.009 Mean Desferal duration/week 61.3 hours 44 hours 0.009 Liver Biopsy: The mean liver iron content in the three patients who underwent liver biopsy one year post L1 dropped from 1469 microgm/100mg dry liver to 325.3microgm/100mg dry liver. Histologically one patient showed an improvement in siderosis, the other in fibrosis and the third patient had no change in histology. Side effects: Three patients developed side effects. One patient had arthralgia and zinc deficiency. One had only arthralgia and the other developed neutropenia 8 months post L1 and hence L1 was discontinued. The patient recovered with GCSF and subsequently had no neutropenia. Arthralgia in these two patients improved with analgesics and they continued on L1. Summary: In this group of paediatric patients L1 has been shown to be effective in reducing iron overload as evidenced by a reduction in mean serum ferritin levels and desferrioxamine requirements. L1 also resulted in a fall in liver iron content and improvement in histology in patients who have undergone liver biopsy a year after being on L1. L1 was well tolerated in all patients with only one patient developing neutropenia which was reversible. In conclusion, deferiprone appears to be a safe and effective drug for treating iron overload in children, and it may allow reduction in the dose and frequency of desferrioxamine use.

T2* MRI Provides No Evidence for Myocardial and Pancreatic Iron Overload in Multitransfused Patients with Sickle/β-Thalassemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1422-1422 ◽  
Author(s):  
Hussam Ghoti ◽  
Orly Goitein ◽  
Elie Konen ◽  
Ariel Koren ◽  
Carina Levin ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Content ◽  
Transferrin Saturation ◽  
Left Ventricular ◽  
Iron Deposition ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Cardiac Iron Overload ◽  
T2 Mri

Abstract Introduction: Transfusion-dependent hemolytic anemias particularly thalassemia major (thal.m) and also sickle cell disease (SCD) result in iron deposition in the reticuloendothelial system in major organs, mainly in the liver and also in the heart and endocrine glands. However, liver iron levels in patients with thal.m measured by other techniques were found to have no predictive values for the extent of their cardiac iron deposition. T2* MRI sequences have been previously addressed as a reliable tool for non invasive evaluation of iron load in the liver, heart and pancreas. Patients with T2* value &gt; 20 ms have normal cardiac function while the prevalence of myocardial dysfunction and arrhythmias increases as a consequence of cardiac iron overload (T2* &lt; 20 ms). A previous study comparing cardiac iron overload in transfusion dependent thal.m and SCD patients matched for age and liver iron content, found abnormally low cardiac T2* values (&lt;20 ms) in nearly 40% of patients with thal.m, while the T2* values were normal in the patients with SCD (1) (Blood:103;1934, 2004). The purpose of the present study was to quantify iron content (T2* values) in the liver, heart and pancreas of multitransfused patients with sickle/β-thal. Patients and Methods: Eleven patients with sickle/β-thal., 3 males and 8 females, mean age 31 years ± 9.5 (SD) were analyzed, 6 of them were splenectomized. Their mean ± SD values for hemoglobin was 9.0 gr/dl, for serum ferritin - 3900 ng/ml ± 3944 and for transferrin saturation - 80% ± 23. All of them were transfused and received a mean of 97 packed cell units ± 88 (SD). Only one patient received iron chelation for 10 months until 6 months prior to entering the study. Seven patients received regularly Hydrea 1–1.5 gr/day for &gt; 10 years. MRI evaluation (1.5T, GE MRI system) included: Left ventricular (LV) function (ejection fraction)- steady-state free procession (SSFP) cine sequence as well as iron load quantification- breath-hold multi echo gradient echo T2*, sampled across regions of interest in the LV septum, liver parenchyma and pancreatic tissue. (Eur. Heart J22:2171, 2001) Results: All patients had normal T2* values in the heart (&gt;20ms) and in the pancreas (&gt;30ms). The left ventricular ejection fraction, left ventricular endsystolic and endiastolic volumes (evaluated both by echo-cardiography and by cine function MRI) were normal in all patients. There was no evidence for pleural or pericardial effusion. The diameter of the pulmonary artery and right ventricle were normal. Seven patients demonstrated evidence of mild to moderate iron deposition in the liver (T2* &lt;6.3 ms). In these patients mean serum ferritin (5656 ng/ml) and transferrin saturation (92.4%) were significantly higher (p=0.001) than in 4 patients with normal T2* levels in the liver (&gt;6.3ms) where mean serum ferritin was 872ng/ml and transferrin saturation 59.5%. Conclusion: The T2* MRI values of 11 patients with sickle/β-thal. showed that whereas 7 patients had a certain degree of iron deposition in the liver, none demonstrated cardiac or pancreatic iron deposition. Therefore, with respect to iron deposition, multitransfused patients with sickle/β-thal. are similar to patients with homozygous SCD and not to patients with thal.m and thal intermedia. The reasons for this observation are still unclear. This similarity could be related in part to the relativly low number of transfusions, starting later in life, of patients with homozygous SCD or sickle/β- thal. compared to patients with thal.m. (1) The liver is the dominant iron storage organ and iron liver concentration correlates closely with the total body iron content. While iron uptake by hepatocytes is predominately mediated via transferrin and correlates with serum ferritin levels, as confirmed in the present study, this is not the case in regulation of cardiac and endocrine iron uptake. These organs might acquire the excess metal differently. It is possible that additional and/or different forms of iron, which have been identified, such as non-transferrin bound iron and labile plasma iron, are involved in determining iron loading in the heart and endocrine glands and/or because regulation of iron entry into the plasma by hepcidin might differ. Additional studies are in progress to address these issues.

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

Blood ◽  
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.

scholarly journals Does Iron Overload Really Matter in Stem Cell Transplantation?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3029-3029
Author(s):  
Philippe Armand ◽  
Marie-Michele Sainvil ◽  
Haesook T Kim ◽  
Joanna Rhodes ◽  
Corey Cutler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Content ◽  
Research Funding ◽  
Acute Gvhd ◽  
Liver Iron ◽  
Liver Iron Content

Abstract Abstract 3029 Background: In patients with hematologic malignancies undergoing myeloablative hematopoietic stem cell transplantation (HSCT), an elevated serum ferritin prior to HSCT has been consistently associated with increased mortality. While serum ferritin is strongly correlated with liver iron content (LIC), to date no study has directly examined the effect of elevated LIC on HSCT outcomes. Furthermore, there are no studies of pre-transplantation chelation in this population. We conducted 2 prospective studies in patients with AML, ALL, or MDS undergoing HSCT. In the first, 45 patients were followed for >1 year with serial measurements of serum iron parameters and liver and cardiac iron (by MRI). In the second, we treated patients with severe iron overload (ferritin ≥ 1000 ng/ml and liver iron content (LIC) ≥ 5 mg/gdw) with deferoxamine 50 mg/kg/d starting in the weeks prior to transplantation and continuing until day -1, with the goal of controlling labile plasma iron (LPI) and especially the expected conditioning-induced rise in LPI. Results: The baseline characteristics of the patients on the observational study have been described in a prior publication (Armand et al., BBMT 2011). 5 patients (2 with AML in CR, 2 with AML and active disease, 1 with MDS) were enrolled on the chelation study; the median serum ferritin was 3, 746 ng/ml, and LIC 11.7 mg/gdw. They received deferoxamine for a median of 19 days before stem cell infusion. No significant drug-related toxicity occurred except for one episode of transient hypotension. There was no significant change in LIC after this short course of chelation. None of the 5 patients had a positive LPI assay before chelation or at the onset of conditioning; however, despite deferoxamine treatment, 2/5 had elevated LPI post-conditioning. Among those 5 patients, there was no disease relapse or death at a median follow-up of 20 months; only 1 patient developed grade II acute GVHD, and no patient developed VOD. Among the 50 patients in both studies combined, there was no significant change in serum ferritin, LIC or cardiac T2* in the first year after HSCT. After a median follow-up of 24 months, the estimated 2y overall survival (OS) and progression-free survival were 54% and 46%, respectively. When patients on the chelation study were excluded, there was a significant difference in OS for patients with pre-HSCT ferritin > 2, 500 ng/ml (2y OS 21% versus 62%, p =0.03) (Figure, panel A), similar to prior studies. However, there was no difference in OS, PFS, relapse or NRM for patients stratified by pre-HSCT LIC, regardless of the cutoff used and whether or not chelated patients were included (Figure, panel B). There was also no discernible impact of LIC on acute GVHD or VOD incidence. The difference in OS based on ferritin was apparent even among the patients with LIC<5 mg/gdw. Those results were confirmed in multivariable analyses. Conclusion: We confirmed prospectively that pre-HSCT ferritin is an important prognostic marker in patients with AML, ALL or MDS undergoing HSCT. However, despite the strong correlation between ferritin and LIC, elevated LIC does not itself appear to be associated with survival. Thus, the prognostic value of ferritin may reflect other factors, such as inflammatory state, rather than iron burden. This calls into question the negative adverse impact attributed to iron overload in this population. Pre-transplantation chelation is challenging and does not reliably prevent the rise in LPI with conditioning. Despite this, our results in a very small number of patients raise the question of a possible beneficial effect of deferoxamine administered before HSCT that may be independent of parenchymal or labile iron chelation. Disclosures: Armand: Novartis Oncology: Research Funding. Neufeld:Novartis: Research Funding; Ferrokin BioSciences: Research Funding.

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

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4829-4829 ◽  
Author(s):  
Mehran Karimi ◽  
Fatemeh Amirmoezi ◽  
Sezaneh Haghpanah ◽  
Seyed pouria Ostad ◽  
Mehrzad Lotfi ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Concentration ◽  
Beta Thalassemia ◽  
P Value ◽  
Hepatic Iron ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Hepatic Iron Overload ◽  
T2 Mri

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.

Sign in / Sign up

Export Citation Format

Share Document