scholarly journals Mobilization of Auto-Stem Cells in the Thalassemia Major and Relationship with Iron Overload

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-7
Author(s):  
Xiaoqin Feng ◽  
Yuelin He ◽  
Bindanda Mvuama Van Timothee ◽  
Jing Du ◽  
Chunfu Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Iron Overload ◽  
Thalassemia Major ◽  
Severe Liver ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Significant Difference ◽  
Cardiac Iron Overload ◽  
Liver Iron Overload

Objectives: The hematopoietic stem cells transplantation (HSCT) is the only curable treatment in current for thalassemia major (TM).The quantity of auto stem cell of TM patients are very important for rescue the patients in case of failure of HSCT, and auto stem cells of TM will be used as target cells for gene therapy (GT) in the near future. Iron overload (IOL) can damage the hematopoiesis of TM. How to collect the auto stem cells in TM patients? How about the affects of iron overload in the mobilization and collection of auto stem cell? The aim of this study was to analyze quantity of auto stem cells in the TM and the affects of iron overload (IOL). Methods: We retrospectively analyzed a total of 134 patients and 25 normal donors undergoing PBSCs collection between January 2012 and December 2019. Patients with serum ferritin levels over 1,000 ng/mL and with a history of red blood cell transfusions prior to stem cell collection were defined as a group having transfusion-associated iron overload (IOL). In total one hundred and thirty-four patients and twenty-five donors were subcutaneous administrated G-CSF (Granulocyte Colony Stimulating Factor) 10 mg/kg/d Injection for 5 days, PBSCs was collected using a large volume leukapheresis (LVL) procedure. The data of WBC, MNC and CD34+ in product were analyzed by SPSS 20 software. Results: In 134 patients, median age is 8.60 range: (1-17),and 25 Normal donors, median age is 7.5 range: (1-18). The results demonstrated that cells either in patients with thalassemia or normal donors were effectively mobilized by G-CSF (10 mg / kg/d),as these children showed a marked increase in white blood cells and MNC cells in peripheral blood, reaching a peak in 4 to 5 days after the injection of G- CSF alone. Comparison of the MNC [(6.7±3.5) ×10⁸/kg vs (7.2±4.77) ×10⁸/kg] and CD34+cells [(10.29±4.5)×10⁶/kg vs (10.9±6.8)×10⁶/kg] in collected product in TM patients and normal donors groups revealed no significant difference. There was no significant difference between different Ferritin level (Mild, Intermediate and Severe) on WBC, MNC, and CD34+ in each group at the time point studied. But there was significant difference on MNC number (Normal liver iron (7.73±2.69)×10⁸/kg, Mild liver iron overload (7.66±4.64)×10⁸/kg, Intermediate (6.18± 2.84) ×10⁸/kg compared to Severe liver iron (4.45±3.34)×10⁸/kg, P=0.039. Significant difference was also can be seen in number of MNC of product in patients with intermediate cardiac iron overload compared to normal cardiac iron overload and mild cardiac iron overload (2.76±0.97) ×10⁶/kg vs(6.86±3.39) ×10⁶/kg and (6.88±3.72)×10⁶/kg, P=0.030. There was a statistically significant difference positive correlation between median age (P=0.011) and MNC/Kg (P=0.030). Conclusion:The quantity of mobilization of PBSC in TM patients had no significant difference compare to normal donor. The MNC in product was statistically decreased in intermediate cardiac iron overload and severe liver iron overload (IOL) subgroup. It indicated that iron overload (IOL) in organs may negatively relate to proliferation and mobilization of stem cells in TM. Further quality study of PBSC such as stem cell culture and ability of proliferation should be more evaluated. The sufficient quantity and high quality auto stem cell from TM patient can be more used in the future. Disclosures No relevant conflicts of interest to declare.

Impact Of Liver Iron Overload On Myocardial T2* Response In Transfusion-Dependent Thalassemia Major Patients Treated With Deferasirox For Up To 3 Years

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1016-1016 ◽  
Author(s):  
John Porter ◽  
Ali T Taher ◽  
Yesim Aydinok ◽  
Maria D Cappellini ◽  
Antonis Kattamis ◽  
...  
Keyword(s):  
Iron Overload ◽  
Board Of Directors ◽  
Research Funding ◽  
Iron Removal ◽  
Advisory Committees ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Significant Difference ◽  
Liver Iron Overload ◽  
The Impact

Abstract Background Patients with myocardial iron overload require effective cardiac iron removal to minimize the risk of cardiac complications. The 3 year EPIC cardiac sub-study showed that the oral iron chelator, deferasirox (DFX), effectively reduced cardiac iron overload. Previous reports demonstrate that cardiac iron removal is slow and suggest that liver iron concentration (LIC) may affect cardiac iron removal rate by chelators (Pennell et al., 2012; Blood). The objective of these analyses was to evaluate the impact of the severity of the liver iron overload on the change in myocardial T2* (mT2*) for patients receiving up to 3 years of DFX treatment in the EPIC sub-study. Methods Inclusion and exclusion criteria have been described previously (Pennell et al., 2012; Haematologica). Patients were categorized into LIC ≤15 and >15 mg Fe/g dry weight (hereafter mg/g) at baseline (BL) and by LIC <7, 7–≤15 and >15 mg/g at 12, 24, and 36 months to assess the impact of BL LIC and changes in LIC overtime on mT2*, respectively. During study, LIC and mT2* were measured every 6 months. Efficacy was assessed in per-protocol population that entered third year extension. Here, mT2* is presented as the geometric mean (Gmean) ± coefficient of variation (CV) unless otherwise specified. Statistical significance was established at α-level of 0.05 using a 2-sided paired t-test for within group comparisons and ANOVA for multiple group comparisons. All p-values were of exploratory nature for this post-hoc analysis. Results Of the 71 patients, who continued into study year 3, 68 patients considered evaluable were included in this analysis (per protocol population); 59 patients had LIC values available at end of study (EOS). Mean age was 20.5 ±7.35 years and 61.8 % of patients were female. Mean actual dose of DFX (mg/kg/day) was 32.1 ±5.5 and 35.1 ±4.9 in patients with BL LIC ≤15 and >15 mg/g, respectively. At EOS, mean actual doses were 32.9 ±5.4 (LIC <7 mg/g), 38.0 ±3.4 (LIC 7–≤15 mg/g), and 37.6 ±3.1 (LIC >15 mg/g). Overall, patients had high BL LIC (Mean, 29.0 ±10.0 mg/g); 61 patients had LIC >15 (30.8 ±8.8) mg/g, only 7 patients had LIC ≤15 (12.7 ±1.1) mg/g, and no patients had LIC <7 mg/g. After 36 months, a significant mean decrease from BL in LIC of -7.6 ±4.6 mg/g (p = 0.0049) and -16.8 ±14.0 mg/g (p <0.001) was observed in patients with LIC ≤15 and >15 mg/g, respectively. Notably, 51.9% of patients with BL LIC >15 mg/g achieved EOS LIC <7 mg/g. Overall, mean mT2* was 12.8 ±4.6 ms. The impact of BL LIC on mT2* and LIC response was as follows: in patients with LIC ≤15 mg/g (Mean BL mT2*, 14.2 ±3.6 ms) and >15 mg/g (BL mT2*, 12.7 ±4.7 ms), mT2* increased by 52% (Mean abs. change, 7.5 ±4.1 ms, p=0.0016) and 46% (7.3 ±7.3 ms, p<0.001), respectively. Patients with BL LIC ≤15 normalized mT2* in 24 months (Mean, 20.0 ±6.0 ms) versus 36 months for patients with BL LIC >15 mg/g, (20.1 ±10.6 ms) displaying a lag of nearly 12 months. The relation between post-BL LIC on mT2* response at 12, 24 and 36 months is shown in the figure. At 12 months, there was no significant difference in mT2* that had occurred in patients with LIC <7 mg/g (24% increase; mean abs. change, 3.5 ±2.3 ms), LIC 7–≤15 mg/g (19% increase; 3.4 ±5.2 ms) and those with LIC >15 mg/g (13% increase; 1.9 ±3.2 ms). However, at 24 months, there was a statistically significant difference amongst the 3 subgroups in percent increase in the mT2* that had occurred; patients with LIC <7, LIC 7-≤15 and LIC >15 mg/g had 54% (Mean abs. change, 8.3 ±7.3 ms), 33% (5.2 ±5.2 ms) and 10% (2.1 ±4.3 ms) increase (p <0.001), respectively. Similarly, at 36 months, the mT2* had increased by 71% (Mean abs. change, 10.3 ±6.6 ms) in the LIC <7 mg/g group; a 31% increase (5.3 ±5.0 ms) had occurred in the LIC 7– ≤15 mg/g group; and an 18% (3.3 ±6.0 ms) increase (p <0.001) had occurred in the LIC >15mg/g group. At all-time points, in patients who achieved an LIC <7 mg/g, a statistically significant increase in T2* from BL had occurred. Discussion Overall, DFX treatment resulted in a significant decrease in LIC and improved mT2*. A greater difference in mT2* improvement was shown to have occurred in patients who achieved lower end-of-year LIC after treated with DFX. This divergence was progressive with time, being maximal at 36 months. Thus, a therapeutic response in LIC with DFX is associated with a greater likelihood of improving mT2*. This may assist in monitoring liver and cardiac response to DFX. Prospective evaluation of this relationship is indicated. Disclosures: Porter: Novartis Pharma: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria; Celgene: Consultancy. Taher:Novartis Pharma: Honoraria, Research Funding. Aydinok:Novartis Oncology: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Cappellini:Novartis Pharma: Honoraria, Speakers Bureau; Genzyme: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Kattamis:Novartis: Research Funding, Speakers Bureau; ApoPharma: Speakers Bureau. El-Ali:Novartis Pharma: Employment. Martin:Novartis Pharma: Employment. Pennell:Novartis: Consultancy, Honoraria, Research Funding; ApoPharma: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria.

Update in Combined Chelation Therapy with Deferoxamine and Deferiprone in Brazilian Patients with Thalassemia Major: Assessment of Three Years

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5415-5415
Author(s):  
Sandra Regina Loggetto ◽  
Mônica Veríssimo ◽  
Antônio Fabron Júnior ◽  
Giorgio Roberto Baldanzi ◽  
Nelson Hamerschlak ◽  
...  
Keyword(s):  
Adverse Events ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Combined Therapy ◽  
Thalassemia Major ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Introduction: Cardiac failure is a main cause of morbidity and mortality in patients with thalassemia major (TM) who are receiving regular blood transfusion due to iron overload. So, effective and adequate iron chelation is extremely important. Deferoxamine (DFO), the most widely used iron chelator, has poor compliance. Combined therapy with Deferiprone (DFP) increases chelation efficacy, decreases iron-induced complications, improves compliance increasing survival in thalassemia. Objectives: Assessment of efficacy and safety in combined chelation with DFP and DFO in thalassemic patients with iron overload. Methods and results: We have 50 thalassemia major patients in 4 Brazilian Centers (Boldrini Hospital, Sao Paulo Hematology Center, HEMEPAR and FAMEMA) receiving combined chelation therapy with follow up to three years. DFP (75–100 mg/kg/daily) and DFO (30–60 mg/kg, 4–7 days/week) are being administered during one to three years. Median age of this group is 21,5 y/o (range 8–35), with 48% female. Median age to start regular transfusions was 12 months (range 2–140) and to begin chelation therapy was 57 months (range 17–216). All patients were screened for Hepatitis C and 26% had positive sorology and/or PCR. Statistical analysis were made with Spearman test and Fisher test. All patients, except two, did cardiac and liver MRI in the initial phase of the study, resulting in 60,5% with cardiac iron overload (T2*&lt;20ms), being severe in 31,2%. Assessment of liver iron concentration (LIC) showed 95,7% with liver iron overload (&gt;3ug/g dry weight), being severe in 17,4%. During follow up, only 43 patients (86%) was screened with MRI. From these, 67,4% had cardiac iron overload (severe in 32,5%) and 78,6% had liver iron overload (severe in 11,9%). Mean serum ferritin before and after three years were 3095,7 ±1934,5 ng/ml and 2373,9±1987,6 ng/ml, respectively. Our data showed positive correlation between serum ferritin, LIC and ALT, even in initial data and after combined chelation therapy (p&lt;0,001), but there is no correlation between cardiac T2* and LIC and between cardiac T2* and ferritin. DFP adverse events included 8% agranulocytosis, 22% neutropenia, 20% arthralgia and 38% gastric intolerance. DFO adverse events were 2,6% deafness, 2,0% cataract and 12% growth deficit. Hepatic toxicity was found in 6%, but without necessity to stop treatment. Compliance in this group was excellent in 48%, good in 22% and poor in 30%. Conclusions: This is the first multicenter study to evaluate combined chelation therapy in Brazil based on cardiac MRI and LIC. Most patients had cardiac and hepatic iron overload probably because they began iron chelation lately, due to difficult access to iron chelators in the past. Cardiac iron overload didn’t have correlation with ferritin and LIC and these data need more understanding. Age of initial regular blood transfusion, increased transfusional requirement, inadequate chelation or delayed chelation may play a role in this question. Combined therapy with DFO and DFP is effective to decrease serum ferritin and LIC. Follow up and improving compliance may decrease cardiac iron overload. Adverse events are similar to literature. Combined therapy is safety in TM patients with transfusional iron overload.

Value of severe liver iron overload for assessing heart iron levels in thalassemia major patients

2016 ◽  
Vol 44 (4) ◽  
pp. 880-889 ◽  
Author(s):  
Xiaodong Chen ◽  
Hui Zhang ◽  
Qihua Yang ◽  
Zebin Luo ◽  
Zuoquan Zhang ◽  
...  
Keyword(s):  
Iron Overload ◽  
Thalassemia Major ◽  
Severe Liver ◽  
Liver Iron ◽  
Liver Iron Overload

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

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5738-5738
Author(s):  
Libai Chen ◽  
Yuelin He ◽  
Jianyun Wen ◽  
Wenjing Yang ◽  
Xuan Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Iron Overload ◽  
Hematopoietic Stem Cell ◽  
Serum Ferritin ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Liver Iron ◽  
Hematopoietic Stem ◽  
Cardiac Iron

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

scholarly journals Hemostatic abnormalities in children with thalassemia major and liver iron overload

2018 ◽  
Vol 58 (4) ◽  
pp. 175-9
Author(s):  
Pustika Amalia Wahidiyat ◽  
Stephen Diah Iskandar ◽  
Novie Amelia Chozie ◽  
Damayanti Sekarsari
Keyword(s):  
Iron Overload ◽  
Prothrombin Time ◽  
Thalassemia Major ◽  
Cross Sectional Study ◽  
Iron Deposition ◽  
Severe Liver ◽  
Liver Iron ◽  
Cross Sectional ◽  
Prolonged Aptt ◽  
Liver Iron Overload

Background Thalassemia major (TM) patients are susceptible to liver dysfunction due to iron deposition. Pediatric TM patients often present with bleeding. Blood loss necessitates transfusions, leading to increased iron absorption from the gut. Objective To study hemostatic abnormalities in children with TM and iron deposition in the liver. Methods This cross-sectional study involved 190 non-splenectomized children with TM. Liver iron deposition was evaluated using T2* MRI. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet counts were assessed from blood specimens. Results Most subjects were diagnosed with β-thalassemia and β-thalassemia/HbE. The majority of subjects were on deferiprone (DFP) treatment. Approximately 89.5% of subjects had liver iron overload. Prolongation of PT and aPTT, as well as thrombocytopenia were observed in 60%, 27.9%, and 19.5% of subjects, respectively. Prolonged aPTT and thrombocytopenia were observed three times more frequently in subjects with moderate - severe liver iron overload than in subjects with normal - mild liver iron overload (P=0.04 and 0.001, respectively). Conclusion Most TM subjects have liver iron overload ranging from mild to severe. Prothrombin time and prolongation, as well as aPTT prolongation, and thrombocytopenia are easily found in TM children. There were significantly more moderate - severe liver iron deposition patients with aPTT prolongation and thrombocytopenia than normal – mild patients with these conditions. Hence, we suggest that pediatric TM patients undergo liver iron deposition evaluations and use iron chelators in an optimal manner, in order to limit the risk of bleeding.

scholarly journals Longitudinal analysis of heart and liver iron in thalassemia major

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2973-2978 ◽  
Author(s):  
Leila J. Noetzli ◽  
Susan M. Carson ◽  
Anne S. Nord ◽  
Thomas D. Coates ◽  
John C. Wood
Keyword(s):  
Longitudinal Analysis ◽  
Time Lag ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Iron Accumulation ◽  
Liver Iron ◽  
Cross Sectional ◽  
Cardiac Iron ◽  
Cardiac Iron Overload ◽  
Magnetic Resonance Imaging Mri

Abstract High hepatic iron concentration (HIC) is associated with cardiac iron overload. However, simultaneous measurements of heart and liver iron often demonstrate no significant linear association. We postulated that slower rates of cardiac iron accumulation and clearance could reconcile these differences. To test this hypothesis, we examined the longitudinal evolution of cardiac and liver iron in 38 thalassemia major patients, using previously validated magnetic resonance imaging (MRI) techniques. On cross-sectional evaluation, cardiac iron was uncorrelated with liver iron, similar to previous studies. However, relative changes in heart and liver iron were compared with one another using a metric representing the temporal delay between them. Cardiac iron significantly lagged liver iron changes in almost half of the patients, implying a functional but delayed association. The degree of time lag correlated with initial HIC (r = 0.47, P < .003) and initial cardiac R2* (r = 0.57, P < .001), but not with patient age. Thus, longitudinal analysis confirms a lag in the loading and unloading of cardiac iron with respect to liver iron, and partially explains the weak cross-sectional association between these parameters. These data reconcile several prior studies and provide both mechanical and clinical insight into cardiac iron accumulation.

β-Thalassemia Mouse Model: Macrophages and the Induction of Iron Overload.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2699-2699
Author(s):  
Yelena Z. Ginzburg ◽  
Radma Mahmood ◽  
Steven Brunnert ◽  
Mary E. Fabry ◽  
Ronald L. Nagel
Keyword(s):  
Iron Overload ◽  
Prussian Blue ◽  
Kupffer Cells ◽  
Thalassemia Major ◽  
Blue Staining ◽  
Cardiac Iron ◽  
Iron Administration ◽  
Cardiac Iron Overload ◽  
Rbc Indices ◽  
Parenteral Iron

Abstract Despite the use of transfusion and iron chelation therapy, patients with β-thalassemia major have a shortened life expectancy. Many of those deaths are attributable to cardiac iron overload. Nevertheless, the process by which cardiac iron overload occurs is not well understood. We have used the homozygous βmajor deletion [Hbbth-1] (THL) mouse model to assess hepatic and cardiac iron load. RBC indices for 3 THL mice and 2 C57BL/6 wildtype control mice prior to and post therapy with parenteral iron were evaluated with Advia. Intraperitoneal iron dextran injection at 10mg/25gm body weight daily 5 days per week for 12 days was performed and then switched to 1.25mg/25gm body weight of iron injection for another 10 days for a total of 4 weeks. Histological samples of liver and heart were stained with Prussian blue in mice prior to and post administration of parenteral iron. Immunohistochemistry with antibody to F4/80, specific for macrophages, was performed and counterstained with Prussian blue in livers and hearts of THL and C57 mice. The RBC indices in THL mice reveal an anemia (HCT 29.5±2.3 vs 45±2.1%, P=0.005) and reticulocytosis (2218±501 vs 406±101 x 109 cells, P=0.018) prior to therapy relative to the C57 mice (values presented as mean ± standard deviation). In THL mice after parenteral iron, HCT (41.8±6.8 vs 29.5±2.3%, P=0.04) and reticulocyte counts (2218±501 vs 3760±633 x 109 cells, P=0.03) increased significantly from pre-treatment values while in C57 mice, the HCT (53.8±6 vs 45±2.1%, NS) and reticulocyte count (406±101 vs 210±49 x109 cells, NS) did not change appreciably from baseline. Prior to therapy, the liver of THL mice exhibit 20–25% Kupffer cells staining with Prussian blue, with no Prussian blue staining in hepatocytes. The hearts of THL mice have no macrophages and no iron deposition at baseline. Prior to therapy, the livers of C57 mice had similar numbers of Kupffer cells compared to THL mice though none stain with Prussian blue. After treatment with parenteral iron, the livers of THL and C57 mice became significantly iron loaded (75–80% of Kupffer cells are positive for Prussian blue), the number of Kupffer cells increased 4-fold, and the majority of the Prussian blue staining was limited to Kupffer cells (90–95%). After treatment with parenteral iron, the hearts of THL and C57 mice became significantly iron loaded as well, but unlike the liver, most (90%) of the Prussian blue positive cells were myocytes. Only a small fraction of the myocytes in the heart was involved (5%). THL mice appear to be iron deficient and show bone marrow reserve with reticulocytosis significantly above baseline when excess iron is administered. Iron overload secondary to intraperitoneal iron dextran administration affects THL mice as well as C57 mice. In the liver of THL mice, Kupffer cells normally resident in the liver become laden with iron; little iron is deposited in hepatocytes. In the heart, an organ without resident macrophages and few macrophages migrating into the tissue during parenteral iron administration, both THL and C57 mice reveal myocyte deposition of iron. In conclusion, parenteral iron administration leads to a noticeable increase in RBCs in THL mice. Furthermore, both the livers and hearts of THL mice accumulate iron. Finally, these findings correlate well with the natural history of cardiac iron overload in human β-thalassemia major, leading to the conclusion that THL mice are a suitable model for the study of cardiac iron overload in thalassemia.

Cardiac Iron Loading Measured by Multislice Multiecho T2* MRI and Cardiac Disease In Male and Female Patients with Thalassemia Major

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4268-4268
Author(s):  
Alessia Pepe ◽  
Maria Marsella ◽  
Antonella Meloni ◽  
Valeria Caldarelli ◽  
Maria Chiara Dell'Amico ◽  
...  
Keyword(s):  
Iron Overload ◽  
Cardiac Disease ◽  
Chelation Therapy ◽  
Thalassemia Major ◽  
Myocardial Iron ◽  
Heart Dysfunction ◽  
Female Patients ◽  
Cardiac Iron ◽  
Significant Difference ◽  
Males And Females

Abstract Abstract 4268 Introduction. Heart disease remains the main cause of mortality in thalassemia major patients. Female patients with thalassemia major have a proved lower prevalence of cardiac complications than males and survive longer. It has been suggested that females have a better compliance than males, and therefore accumulate less iron in crucial organs like the heart (Borgna-Pignatti C et al, Haematologica 2004). The aim of our study was to verify if the decreased prevalence of cardiac disease in females could be attributed to lesser iron accumulation in their hearts as measured by multislice multiecho T2* Magnetic Resonance Imaging (MRI) technique. Methods. We performed a retrospective review of the MRI results and of clinical data about the thalassemia major patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) project. The MIOT is a network where MRI is performed using standardized and validated procedures and the MRI and thalassemia centers are linked by a web-based network, configured to collect patients' clinical and diagnostic data (Meloni A et al, Int J Med Inform 2009). Myocardial iron concentrations were measured by T2* multislice multiecho technique (Pepe A et al, JMRI 2006).Biventricular function parameters were quantitatively evaluated by cine images. Results. Seven hundred and seventy six thalassemia patients (370 males) were present in the MIOT database having undergone at least one MRI exam. The prevalence of cardiac disease (heart dysfunction and/or arrhythmias requiring medications) was significantly higher in males than in females (males 28% vs females 17%; P<0.0001). The analysis of different chelation treatments did not demonstrate a significant difference between patients with and without cardiac disease (P=0.59), nor between sexes (P=0.46). In addition, there was no difference in the reported compliance to chelation therapy between males and females (P=0.52). Global heart T2* values were significantly lower in both males and females with heart dysfunction (males: 20 ± 15 ms; females: 18 ± 12 ms), compared to those without dysfunction (males: 29 ± 11 ms; females: 27 ± 13 ms) (P<0.0001), but no difference was observed according to sex (Figure 1A). Global heart T2* values were not significantly lower in patients with arrhythmias compared to those without arrhythmias, nor was there a significant difference between sexes (Figure 1B). Conclusions. The confirmed higher prevalence of cardiac disease in males with thalassemia major was not correlated to a worse compliance to chelation therapy or to an higher cardiac iron burden. Increased survival of female thalassemia major patients seems to not be attributed to lower cardiac iron overload. It can be hypothesized that females tolerate iron toxicity better, possibly as an effect of reduced sensitivity to chronic oxidative stress. Disclosures: No relevant conflicts of interest to declare.

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