MRI Prospective Survey on Cardiac and Hepatic Iron in Thalassemia Intermedia Patients Treated with Desferrioxamine, Deferiprone and Deferasirox

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4041-4041
Author(s):  
Antonella Meloni ◽  
Aurelio Maggio ◽  
Anna Pietrapertosa ◽  
Pier Paolo Bitti ◽  
Sabrina Armari ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Hepatic Iron ◽  
Thalassemia Intermedia ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Number Of Patients ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri

Abstract Background. Few studies have evaluated the efficacy of iron chelation therapy in thalassemia intermedia (TI) patients. Our study aimed to prospectively assess by quantitative Magnetic Resonance imaging (MRI) the efficacy of the three available chelators in monotherapy in transfusion dependent (TD) TI patients. Methods. Among the 325 TI patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we selected 103 TI patients TD with an MRI follow-up (FU) study at 18±3 months who had been received one chelator alone between the two MRI scans. Iron overload was assessed by the T2* multiecho technique. Hepatic T2* values were converted into liver iron concentration (LIC) values. Results. Three groups of patients were identified: 27 patients (13 females, mean age 40.12±10.31 years) treated with desferioxamine (DFO – mean dosage 37.52±8.69 mg/kg/die), 23 patients (14 females, mean age 34.73±10.67 years) treated with deferiprone (DFP– dosage 71.70±14.46mg/kg/die) and 14 patients (9 females, mean age 36.63±10.92 years) treated with deferasirox (DFX – mean dosage 27.75±5.04 mg/kg/die). Excellent/good levels of compliance were similar in the DFO (92.6%), DFP (100%) and DFX (100%) groups (P=0.345). The mean starting age of regular transfusion was 14.73±15.89 years. At baseline in DFO group two patients (7.4%) showed a global heart T2*<20 ms and one of them showed no cardiac iron at the FU. At baseline in DFP group two patients (8.7%) showed a global heart T2*<20 ms and one of them showed no cardiac iron at the FU. All the 5 patients (35.7%) under DFX therapy with pathological global heart T2* at the baseline remained at the same status at the FU. The percentage of patients who maintained a normal global heart T2* value was comparable for DFO (100%), DFP (100%) and DFX (88.9%) groups (P=0.164). Among the 46 patients with hepatic iron at baseline (MRI LIC ≥3 mg/g/dw), the reduction in the MRI LIC values was significant only in the DFO group (DFO: -3.39±6.38 mg/g/dw P=0.041; DFP: -2.25±6.01 mg/g/dw P=0.136 and DFX: -0.36±5.56 mg/g/dw P=0.875). The decrease in MRI LIC values was comparable among the groups (P=0.336). The number of patients with a MRI LIC<3 mg/g/dw went up from 10 (37%) to 11 (40.7%) in the DFO group, from 6 (26.1%) to 8 (34.8%) in the DFP group and from 2 (14.3%) to 8 (57.1%) in the DFX group. The percentage of patients who maintained a normal MRI LIC value was comparable for DFO (90%) vs DFP (50%) and DFX (100%) groups (P=0.191). Conclusion: Prospectively in transfusion-dependent TI patients at the dosages used in the clinical practice, DFO and DFP showed 100% efficacy in maintaining a normal global heart T2* value while DFX had 100% efficacy in maintaining a normal LIC value. Further prospective studies involving more patients with iron at the baseline are needed to establish which is the most effective drug in reducing iron levels. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.

scholarly journals A T2* MRI Prospective Survey on Cardiac and Hepatic Iron in Non-Trasfusion-Dependent Thalassemia Intermedia Patients Treated with Desferrioxamine

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4900-4900
Author(s):  
Antonella Meloni ◽  
Aurelio Maggio ◽  
Carlo Cosmi ◽  
Alfonso D'Ambrosio ◽  
Elena Facchini ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Real Life ◽  
Hepatic Iron ◽  
Thalassemia Intermedia ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Hepatic Iron Overload ◽  
Cardiac Iron Overload

Abstract Background. In thalassemia intermedia (TI) patients no observational study prospectively evaluated in the real life the efficacy of the desferrioxamine (DFO) therapy in removing or preventing iron overload from the heart and the liver by T2* Magnetic Resonance Imaging (MRI). The efficacy endpoint of this study is represented by the changes in cardiac T2* and MRI LIC (liver iron concentration) values in non-transfusion dependent (NTD) TI patients after 18 months of desferrioxamine therapy. Methods. Among the 325 TI patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we selected 129 TI patients NTD. We considered 29 patients who had been received DFO alone between the two MRI scans. Cardiac iron overload was assessed by the T2* multiecho technique. Hepatic T2* values were converted into liver iron concentration (LIC) values. Results. Mean age was 39.69 ± 8.12 years and 14 (48.3%) patients were females. Patients started regular chelation therapy at a mean age of 21.92 ± 15.89 years. The mean administered dosage of DFO via subcutaneous route was 38.46 ± 10.27 mg/kg body weight on 3.32 ± 1.54 days/week. The percentage of patients with excellent/good levels of compliance to the chelation treatment was 82.1%. At baseline only one patient showed cardiac iron overload (global heart T2*=15.23 ms) but he recovered at the FU (global heart T2*=26.93 ms). All patients without cardiac iron maintained the same status at the follow-up (FU). Eighteen patients (62.1%) had hepatic iron overload (MRI LIC ≥3 mg/g/dw) at the baseline. For this subgroup, the baseline and the FU LIC values were, respectively, 9.15 ± 7.97 mg/g/dw and 7.41 ± 6.28 mg/g/dw. The reduction in MRI LIC values was not significant (P=0.102). Out of the 11 patients with a baseline MRI LIC <3 mg/g/dw, only one (9.1%) showed hepatic iron at the FU. The Figure shows the evolution of different hepatic iron overload risk classes between the baseline and the FU. Conclusions. In this small population of sporadically or non transfused TI patients, DFO showed 100% efficacy in maintaining a normal global heart T2* value. As regards as the hepatic iron overload, the DFO therapy did not prevent the transition to a worst class in 2 patients. Figure 1 Figure 1. Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.

scholarly journals Hepatocellular Carcinoma in β-Thalassemia Patients: Review of the Literature with Molecular Insight into Liver Carcinogenesis

2018 ◽  
Vol 19 (12) ◽  
pp. 4070 ◽  
Author(s):  
Antoine Finianos ◽  
Charbel Matar ◽  
Ali Taher
Keyword(s):  
Hepatocellular Carcinoma ◽  
Iron Overload ◽  
Treatment Success ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Multicenter Studies ◽  
Major Life ◽  
Liver Iron ◽  
Magnetic Resonance Imaging Mri ◽  
Personalized Approach

With the continuing progress in managing patients with thalassemia, especially in the setting of iron overload and iron chelation, the life span of these patients is increasing, while concomitantly increasing incidences of many diseases that were less likely to show when survival was rather limited. Hepatocellular carcinoma (HCC) is a major life-threatening cancer that is becoming more frequently identified in this population of patients. The two established risk factors for the development of HCC in thalassemia include iron overload and viral hepatitis with or without cirrhosis. Increased iron burden is becoming a major HCC risk factor in this patient population, especially in those in the older age group. As such, screening thalassemia patients using liver iron concentration (LIC) measurement by means of magnetic resonance imaging (MRI) and liver ultrasound is strongly recommended for the early detection of iron overload and for implementation of early iron chelation in an attempt to prevent organ-damaging iron overload and possibly HCC. There remain lacking data on HCC treatment outcomes in patients who have thalassemia. However, a personalized approach tailored to each patient’s comorbidities is essential to treatment success. Multicenter studies investigating the long-term outcomes of currently available therapeutic options in the thalassemia realm, in addition to novel HCC therapeutic targets, are needed to further improve the prognosis of these patients.

Myocardial and Hepatic Iron Overload and Cardiac Function In Sickle/Thalassemia Patients Of Italian Origin

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2252-2252
Author(s):  
Antonella Meloni ◽  
Giovan Battista Ruffo ◽  
Daniele De Marchi ◽  
Antonio Cardinale ◽  
Anna Pietrapertosa ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Iron Overload ◽  
Conflicts Of Interest ◽  
Iron Concentration ◽  
Hepatic Iron ◽  
Liver Iron ◽  
Hepatic Iron Overload ◽  
The Mean ◽  
Magnetic Resonance Imaging Mri ◽  
Italian Origin

Abstract Introduction Sickle-thalassemia results from the combined heterozygosity for sickle-cell and β-thalassemia genes. This study evaluates myocardial and hepatic iron overload and cardiac function in Italian patients and explores their correlation with transfusions, age and sex. Methods Fifty-nine sickle-thalassemia patients (29 males, mean age 35.6±14.1 years), enrolled in the MIOT network underwent magnetic resonance imaging (MRI). T2* value for all 16 myocardial segments and global heart T2* value were calculated. Hepatic T2* value was converted into liver iron concentration (LIC). Cine images were acquired to quantify biventricular volumes and ejection fraction (EF). Results 55 (93%) patients had all segmental T2* values normal (>20 ms). Of the 4 patients with abnormal segmental T2* values, all showed an heterogeneous myocardial iron overload (some segments with T2*>20 ms and other with T2*<20 ms) and only one had a global T2*<20 ms. The mean global heart T2* value was 34.4±6.2 ms. The mean LIC was 5.9±6.5 mg/g/dw and 30 patients (50.8%) had a pathological value (≥ 3 mg/g dw). There was a statistically significant positive correlation between global heart T2* and age but with poor linearity (R=0.368; P=0.004) and there was not a significant correlation between age and LIC. Males and females had comparable global heart T2* values and LIC values. Twenty patients were regularly transfused, 32 received sporadic transfusions while 7 were not transfused. The comparison among the three groups is shown in Table 1. We did not find significant differences in the global heart T2* value while patients regularly transfused had significantly higher LIC than sporadically transfused patients. Biventricular volumes indexed by body surface area and ejection fractions were comparable among the groups. Conclusions In respect of MIO, the sickle/thalassemia patients are similar to patients with homozygous SCD for which iron overloading is relatively rare. Hepatic iron overload may develop also in no regularly-transfused patients, maybe due to increased absorption of iron from the digestive tract, characteristic of both SCD and thalassemia intermedia patients. This finding underlines the importance to monitor by MRI also no regularly transfused sickle/thalassemia patients. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3818-3818
Author(s):  
Ali Taher ◽  
F. El Rassi ◽  
H. Ismaeel ◽  
S. Koussa ◽  
A. Inati
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Care Center ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Thalassemia Intermedia ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Cross Sectional ◽  
Transfusion Therapy

Abstract 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&lt;0.001), and in a subset of splenectomized patients (R=0.62; P&lt;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. Figure Figure

The Effect of Supplemental Ascorbate on Defersirox Iron Chelation In the Iron-Loaded Gerbil

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2059-2059
Author(s):  
Maya Otto-Duessel ◽  
Casey Brewer ◽  
Aleya Hyderi ◽  
Jens Lykkesfeldt ◽  
Ignacio Gonzalez-Gomez ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Content ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Iron Dextran ◽  
Iron Loading ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Liver Iron Content ◽  
Wet Weight

Abstract Abstract 2059 Introduction: Iron dextran injections are often used to induce iron overload in rodents, for the purposes of assessing iron chelation therapy. In gerbils, we have previously described that deferasirox therapy preferentially clears hepatocellular iron when compared with reticuloendothelial stores. Ascorbate deficiency, which is common in humans with iron overload, produces similar profound disparities between reticuloendothelial and parenchymal iron stores. We postulated that iron-induced ascorbate deficiency might be exaggerating reticuloendothelial iron retention in gerbils receiving deferasirox therapy. This study examined the effect of supplemental ascorbate on spontaneous iron loss and deferasirox chelation efficiency in the iron-dextran loaded gerbil. Methods: 48 female gerbils underwent iron dextran loading at 200 mg/kg/week for 10 weeks. Sixteen animals were sacrificed at 11 weeks to characterize iron loading; eight were on standard rodent chow and eight had chow supplemented with 2250 ppm of ascorbate. 32 additional animals that were not ascorbate supplemented during iron loading transitioned into the chelation phase. Half were subsequently placed on ascorbate supplemented chow and both groups were assigned to receive either deferasirox 100 mg/kg/day five days per week or sham chelation. Animals received iron chelation for twelve weeks. Liver histology was assessed using H & E and Prussian blue stains. Iron loading was ranked and graded on a five-point scale by an experienced pathologist screened to the treatment arm. Iron quantitation in liver and heart was performed by atomic absorption. Results: Table 1 one summarizes the findings. During iron dextran loading, ascorbate supplementation lowered wet weight liver iron concentration but not liver iron content suggesting primarily changes in tissue water content. Spontaneous iron losses were insignificant, regardless of ascorbate therapy. Deferasirox lowered liver iron content 56% (4.7% per week) in animals without ascorbate supplementation and 48.3% (4.0% per week) with ascorbate supplementation (p=NS). Cardiac iron loading, unloading and redistribution were completely unaffected by ascorbate supplementation. Spontaneous iron redistribution was large (1.9% – 2.3% per week). Deferasirox chelation did not lower cardiac iron to a greater degree than spontaneous cardiac iron redistribution. Histologic grading paralleled tissue wet weight iron concentrations. Ascorbate treatment lowered the rank and absolute iron score in liver during iron loading (p=0.003) and there was a trend toward lower iron scoring in sham treated animals (p=0.13). Ascorbate had no effect on histological score or relative compartment distributions of iron in deferasirox chelated animals (p=0.5). Ascorbate supplementation was sufficient to increase total plasma ascorbate levels from 25 ± 12.2 uM to 38.4 ± 11 uM at 10 weeks (p=0.03). In the liver, ascorbate increased from 1203 ± 212 nmol/g of tissue to 1515 ± 194 nmol/g of tissue (p=0.01) with supplementation. No significant change in total ascorbate was observed in the heart. Discussion: We hypothesized that ascorbate supplementation might improve reticuloendothelial iron accessibility to deferasirox by facilitating redox cycling. Although gerbils synthesize their own ascorbate, supplementation was able to raise both serum and hepatic total ascorbate levels. However, increasing ascorbate did not change either the amount or distribution of tissue iron in deferasirox-treated animals. Disclosures: Nick: Novartis: Employment. Wood:Novartis: Research Funding; Ferrokin Biosciences: Consultancy.

scholarly journals Hepatic iron load differs strikingly between peritoneal dialysis and hemodialysis patients

2019 ◽  
Vol 2 (4) ◽  
pp. 181-191
Author(s):  
Guy Rostoker ◽  
Mireille Griuncelli ◽  
Nasredine Ghali ◽  
Séverine Beaudreuil ◽  
Yves Cohen ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Iron Overload ◽  
Iron Concentration ◽  
Dry Weight ◽  
Hemodialysis Patients ◽  
Hepatic Iron ◽  
Dialysis Patients ◽  
Liver Iron ◽  
Iron Load ◽  
Magnetic Resonance Imaging Mri

Introduction Iron overload is one of the most controversial topics in the management of anemic dialysis patients. Parenteral iron supplementation is commonly prescribed to hemodialysis (HD) patients but less frequently to peritoneal dialysis (PD) patients. Moreover, ferritin targets are far lower and more physiological in PD than in HD.  Methods We compared the liver iron concentration (LIC) measured by means of Signal-Intensity ratio (SIR) magnetic resonance imaging (MRI) according to Rennes University method in a cohort of 32 PD patients living in the Paris region published in 2017, with two cohorts of French HD patients studied in the same way (119 patients reported in 2012 and 80 further patients reported in 2014). Results Normal hepatic iron load (LIC ≤ 50 µmol/g of dry weight) was observed in 81.3% of the 32 PD patients (CI: 64.3-91.5%), as compared to only 16% (CI: 10.4-23.7%) in the first HD cohort and 35% (CI: 25.4-45.9%) in the second HD cohort (p<0.0001 for both comparisons; X2 test). Mild iron overload (50 < LIC ≤ 100 µmol/g) was found in 5 PD patients and severe overload (LIC > 200 µmol/g) in only one PD patient (who had received IV iron) (3.1%; CI: 0-17.1%). Conversely, severe iron overload was found in 30.3% of patients in the first HD cohort (CI: 22.7-39%) and 11.3% of those in the second HD cohort (CI: 5.8-20.2%) (p= 0.0033 versus the first HD cohort, X2 test). Conclusion Contrary to hemodialysis patients, iron overload is rare and mostly mild in peritoneal dialysis patients.

scholarly journals Stratification for Age in Transfusion-Dependent Thalassemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3638-3638
Author(s):  
Alessia Pepe ◽  
Laura Pistoia ◽  
Mario Rocca ◽  
Giovanni Palazzi ◽  
Francesco Sorrentino ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Cardiac Complications ◽  
Liver Iron ◽  
Number Of Patients ◽  
Cardiac Iron Overload ◽  
Group 2 ◽  
Magnetic Resonance Imaging Mri ◽  
Group 1

Abstract Introduction. Transfusion-dependent β-thalassemia (TDT) is the most severe clinical form of β-thalassemia and requires regular long-term red cell transfusions for survival. This study aimed to examine the association of age with the presence of iron overload assessed by Magnetic Resonance Imaging (MRI) and cardiovascular and endocrine complications in TDT patients. Methods. We considered all TDT patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) project at the first MRI examination. Iron concentrations were measured by T2* multiecho technique. All complications were classified according to international guidelines. Results. Three groups of patients were identified: age<12 years (group 0, N=53), age between 12-17 years (group 1, N=100) and age≥18 years (group 2, N=1857). The number of transfusional units in the 12 months before the MRI scan resulted significantly lower in group 0 versus both group 1 (20.8±5.3 vs 34.8±10.6; P<0.0001) and group 2 (20.8±5.3 vs 39.2±10.9; P>0.0001) and in group 1 versus group 2 (P=0.021). The Table shows the comparison of clinical characteristics among the 3 groups. Serum ferritin levels were significantly higher in both groups 0 and 1 when compared to group 2. Liver aminotransferases were significantly lower in group 1 than in group 2. The number of patients with MRI LIC (liver iron concentration) >3 mg/g dw was significantly higher in group 1 than in group 2 and the number of patients with global heart T2*<20 ms was significantly lower in group 0 than in group 2. Among the endocrinopathies, hypogonadism, hypothyroidism and osteoporosis were significantly less frequent in groups 0 and 1 than in group 2 while diabetes was significantly less frequent only in group 1 when compared to group 2. Frequency of heart failure was comparable among the groups while the frequency of arrhythmias was significantly lower in group 1 than in group 2. The types of chelation regimens were significantly different among groups (<0.0001) (see Figure). Conclusions. Younger patients had more hepatic iron, despite the significant lower transfusional burden. Cardiac iron overload occurs early in TDT patients but it is more frequent in older patients. Endocrinopathies (excluding diabetes) and cardiac complications become clinically evident during the second decade and are time-dependent processes. Our data suggest the need for an effective strategy to prevent iron overload since early childhood, in order to reduce its toxic effect and prevent the development of long-term complications. Figure. Figure. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

Association Between Cardiac Iron Clereance and Hepatic Siderosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4833-4833
Author(s):  
Alessia Pepe ◽  
Laura Pistoia ◽  
Domenico D'Ascola ◽  
Maria Rita Gamberini ◽  
Francesco Gagliardotto ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Hepatic Iron ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Follow Up Study ◽  
Hepatic Iron Overload

Abstract Introduction. The aim of this multicenter study was to evaluate in thalassemia major (TM) if the cardiac efficacy of the three iron chelators in monotherapy was influenced by hepatic iron levels over a follow up of 18 months. Methods. Among the 2551 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we evaluated prospectively the 98 patients those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans and who showed evidence of significant cardiac iron (global heart T2*<20 ms) at the basal MRI. Iron overload (IO) was measured by T2* multiecho technique. We used cardiac R2* (equal to 1000/T2*) because cardiac R2* is linearly proportional to cardiac iron and hepatic T2* values were converted into liver iron concentration (LIC) values. Results. We identified 3 groups of patients: 47 treated with deferasirox (DFX), 11 treated with deferiprone (DFP) and 40 treated with desferrioxamine (DFO). Percentage changes in cardiac R2* values correlated with changes in LIC in both DFX (R=0.469; P=0.001) and DFP (R=0.775; P=0.007) groups. All patients in these 2 groups who lowered their LIC by more than 50% improved their cardiac iron (see Figure 1). Percentage changes in cardiac R2* were linearly associated to the log of final LIC values in both DFX (R=0.437; P=0.002) and DFP groups (R=0.909; P<0.0001). Percentage changes in cardiac R2* were not predicted by initial cardiac R2* and LIC values. In each chelation group patients were divided in subgroups according to the severity of baseline hepatic iron overload (no, mild, moderate, and severe IO). The changes in cardiac R2* were comparable among subgroups (P=NS) (Figure 2). Conclusion. In patients treated with DFX and DFP percentage changes in cardiac R2* over 18 months were associated with final LIC and percentage LIC changes. In each chelation group percentage changes in cardiac R2* were no influenced by initial LIC or initial cardiac R2*. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc..

scholarly journals Stratification for Age in Non-Transfusion-Dependent Thalassemia: Data from a National Italian Networking

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3639-3639
Author(s):  
Alessia Pepe ◽  
Laura Pistoia ◽  
Nicola Romano ◽  
Giuseppe Colaci ◽  
Aurelio Maggio ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Iron Overload ◽  
Pediatric Patients ◽  
Cardiac Complications ◽  
Hepatic Iron ◽  
Resonance Imaging ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Magnetic Resonance Imaging Mri

Abstract Background: Non-transfusion-dependent thalassemia (NTDT) is a term used to indicate patients who do not require lifelong regular transfusions for survival. Morbidity in NTDT patients is more common and serious than previously recognized. This study aimed to examine the association of age with the presence of iron overload assessed by Magnetic Resonance Imaging (MRI) and cardiovascular and endocrine complications in NTDT patients. Methods: We considered 170 patients with thalassemia intermedia never transfused o who received occasional transfusions consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) project. Iron overload was quantified by the T2* Magnetic Resonance Imaging (MRI) technique. All complications were classified according to international guidelines. Results: Six groups of patients were identified: age<18 years (N=7), age 18-30 years (N=36), age 30-40 years (N=48), age 40-50 (N=45), age 50-60 years (N=26), and age≥60 years (N=8). The Table shows the comparison among the groups. The youngest patient showing hepatic iron (MRI liver iron concentration-LIC>3 mg/g dw) had 9 years of age and the frequency of hepatic iron did not significantly increase with age. Only one patient showed cardiac iron (global heart T2*<20 ms). Diabetes appeared only in patients with more than 50 years and showed a trend toward increasing with increasing age. Hypothyroidism and osteoporosis were not present in pediatric patients and were not associated to age. Hypogonadism was not present in patients with less than 30 years and its frequency was comparable among the age groups. No patient showed hypoparathyroidism. Only patients older than 30 years showed a cardiac complication (heart failure or arrhythmias), but the rate did not significantly increase with increasing age. Conclusions: Our data in NTDT are indicative of high rate of liver iron overload at early age and extremely rare cardiac iron overload. Endocrine or cardiac complications were not present in pediatric patients but in adult patients the frequency did not increase with advancing age. Table. Table. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

Lack of Correlation between Serum Ferritin and Liver Iron Concentration in Beta-Zero Thalassemia Intermedia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3620-3620 ◽  
Author(s):  
Renzo Galanello ◽  
Nicolina Giagu ◽  
Susanna Barella ◽  
Liliana Maccioni ◽  
Raffaella Origa
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Regulatory Protein ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Dry Weight ◽  
Thalassemia Major ◽  
Thalassemia Intermedia ◽  
Liver Iron Concentration ◽  
Liver Iron

Abstract Serum ferritin and liver iron concentration (LIC) are the most commonly used methods for assessment of iron overload in thalassemia. While in patients with thalassemia major a significant correlation has been found between these two parameters, data are lacking in patients with thalassemia intermedia. In this study we measured the serum ferritin and LIC in 22 adult patients with beta-zero thalassemia intermedia never transfused (14 patients) or sporadically transfused, i.e. less than 10 units in total (8 patients), who maintained a mean hemoglobin of 8.8 ± 1.1 g/dl. Serum ferritin levels were measured by an automated chemiluminescence immunoassay analyzer, whereas LIC was determined by atomic absorption in liver biopsies. We compared the results obtained in those patients with those obtained in 22 regularly transfused (mean annual Hb = 11.3 ± 0.3 g/dl) and iron chelated thalassemia major patients, matched by sex, age and liver iron concentration. We also determined serum erythropoietin (s-epo) and serum transferrin receptor (s-TfR) in a cohort of the two patient groups (12 thalassemia intermedia; 15 thalassemia major). Mean LIC was 11.3 ± 6 mg/g dry weight tissue in thalassemia intermedia, and 11.8 ± 7 mg/g d.w. in thalassemia major group. Mean serum ferritin (at least 2 determinations from each patient within ± 2 months of liver biopsy) was 627 ± 309 ng/ml in thalassemia intermedia and 2748 ± 2510 ng/ml in thalassemia major. The difference was statistically significant (p = 0.0001). LIC was weakly correlated with serum ferritin in thalassemia major patients (r2=0.46; p=0.001) and uncorrelated in patients with thalassemia intermedia (r2=0.04; p=0.37) (Figure). S-epo and s-TfR were significantly higher in thalassemia intermedia than in thalassemia major [s-epo 467 ± 454 mU/ml versus 71 ± 44 mU/ml (p<0.001); s-TfR 43 ± 13 mU/ ml versus 13 ± 6 mU/ml (p<0.0001)]. The discrepancy between LIC and serum ferritin in thalassemia intermedia patients may be due to the higher levels of s-epo (secondary to anemia) in those patients, which through the iron regulatory protein 1 determine an up-regulation of s-TfR and a repression of ferritin translation (Weiss et al 1997). The mechanism of iron overload may also be mediated by hepcidin, whose synthesis could be suppressed as a consequence of anemia. The observation reported has important implications for iron chelation in patients with thalassemia intermedia. In such patients serum ferritin levels have little value for the monitoring of iron overload. Figure Figure

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