scholarly journals SEVERE LIVER IRON CONCENTRATIONS (LIC) IN 24 PATIENTS WITH Β-THALASSEMIA MAJOR: CORRELATIONS WITH SERUM FERRITIN, LIVER ENZYMES AND ENDOCRINE COMPLICATIONS

2018 ◽  
Vol 10 ◽  
pp. e2018062 ◽  
Author(s):  
Vincenzo De Sanctis
Keyword(s):  
Iron Overload ◽  
Adrenal Insufficiency ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Dry Weight ◽  
Thalassemia Major ◽  
Liver Iron

Abstract. Introduction: Chronic blood transfusion is the mainstay of care for individuals with β-thalassemia major (BTM). However, it causes iron-overload that requires monitoring and management by long-term iron chelation therapy in order to prevent endocrinopathies and cardiomyopathies, that can be fatal. Hepatic R2 MRI method (FerriScan®) has been validated as the gold standard for evaluation and monitoring liver iron concentration (LIC) that reflects the total body iron-overload. Although adequate oral iron chelation therapy (OIC) is promising for the treatment of transfusional iron-overload, some patients are less compliant with it and others suffer from long-term effects of iron overload. Objective: The aim of our study was to evaluate the prevalence of endocrinopathies and liver dysfunction, in relation to LIC and serum ferritin level, in a selected group of adolescents and young adult BTM patients with severe hepatic iron overload (LIC from 15 to 43 mg Fe/g dry weight). Patients and Methods: Twenty-four selected BTM patients with severe LIC, due to transfusion-related iron-overload, followed at the Hematology Section, National Center for Cancer Care and Research, Hamad Medical Corporation of Doha (Qatar), from April 2015 to July 2017, were retrospectively evaluated. The prevalence of short stature, hypogonadism, hypothyroidism, hypoparathyroidism, impaired fasting glucose (IFG), diabetes, and adrenal insufficiency was defined and assessed according to the International Network of Clinicians for Endocrinopathies in Thalassemia (ICET) and American Diabetes Association criteria. Results: Patients have been transfused over the past 19.75 ± 8.05 years (ranging from 7 to 33 years). The most common transfusion frequency was every 3 weeks (70.8%).  At the time of LIC measurements, the mean age of patients was 21.75 ± 8.05 years, mean LIC was 32.05 ± 10.53 mg Fe/g dry weight (range: 15 to 43 mg Fe/g dry weight). Their mean serum ferritin level was 4,488.6 ± 2,779 µg/L. The overall prevalence of growth failure was 26.1% (6/23), IFG was 16.7% (4/24), sub-clinical hypothyroidism was 14.3% (3/21), hypogonadism was 14.3% (2/14), diabetes mellitus was 12.5% (3/24), and biochemical adrenal insufficiency was 6.7% (1/15). The prevalence of hepatitis C positivity was 20.8% (5/24). No case of clinical hypothyroidism, adrenal insufficiency or hypoparathyroidism was detected in this cohort of patients. The prevalence of IFG impaired fasting glucose was significantly higher in BTM patients with very high LIC (>30 mg Fe/g dry liver) versus those with lower LIC (p = 0.044). LIC was correlated significantly with serum ferritin levels (r = 0.512; p = 0.011), lactate dehydrogenase (r = 0.744; p = 0.022) and total bilirubin (r = 0.432; p = 0.035). Conclusions: A significant number of BTM patients, with high LIC and endocrine disorders, still exist despite the recent developments of new oral iron chelating agents. Therefore, physicians’ strategies shall optimize early identification of those patients in order to optimise their chelation therapy and to avoid iron-induced organ damage. We believe that further studies are needed to evaluate if serial measurements of quantitative LIC may predict the risk for endocrine complications. Until these data are available, we recommend a close monitoring of endocrine and other complications, according to the international guidelines.  

A Multi-Center, Open Label Study Evaluating the Efficacy of Iron Chelation Therapy with Deferasirox in Transfusional Iron Overload Patients with Myelodysplastic Syndromes or Aplastic Anemia Using Quantitative R2 MRI

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3649-3649 ◽  
Author(s):  
Yoo-Hong Min ◽  
Hyeoung Joon Kim ◽  
Kyoo Hyung Lee ◽  
Sung-Soo Yoon ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Chelation Therapy ◽  
Transfusion Requirement ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Dry Weight ◽  
Mean Value ◽  
One Year

Abstract Transfusion-related iron overload and its consequences are emerging challenges in chronically transfused patients with myelodysplastic syndromes (MDS) or aplastic anemia (AA). Measurement of liver iron concentration (LIC) is used as a surrogate for total iron burden to guide chelation therapy in transfusion-dependent patients. Although deferasirox (Exjade®, ICL670) is an oral iron chelation agent that is now widely available for the treatment of transfusional hemosiderosis, the clinical data on its specific benefits of iron chelation, including reduction of LIC, in transfusion-related iron overload patients with MDS or AA has been limited. We have prospectively investigated the efficacy of deferasirox for iron chelation by serial measurement of serum ferritin level and LIC, which is measured in vivo using quantitative tissue proton transverse relaxation rates (R2) magnetic resonance imaging (MRI), in transfusional iron overload patients with MDS or AA. Here we report the interim analysis data. A total of 79 patients with de novo MDS (n = 29) or idiopathic AA (n = 50) showing serum ferritin level over 1,000ng/ml were enrolled from 23 institutes. All patients were regularly transfused and received a median of 30 red blood cells (RBC) units in the year prior to the start of the study. Among MDS cases, 3 (10.3%), 20 (69.0%), and 4 cases (13.8%) were categorized as IPSS low-risk, intermediate-1-risk, and intermediate-2-risk group, respectively. In AA cases, 34 (64%) were severe form. Mean value of serum ferritin level in enrolled patients was 4,417 ± 3,378 (4,788 ± 3,996 in MDS, 4,185 ± 2,962 in AA) ng/ml at the time of deferasirox initiation. LIC value was measured using quantitative R2 MRI and FerriScan (Resonance Health, Australia) analysis. Mean value of LIC was 23.9 ± 13.8 (26.1 ± 15.0 in MDS, 22.8 ± 13.2 in AA) mg Fe/g dry weight. Linear regression analysis indicated a close correlation between serum ferritin level and LIC (r=0.55, p<0.001). Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients. If the serum ferritin falls below 500 ng/ml, treatment was withheld. A consistent decrease in the serum ferritin level was demonstrated during the first 6 months in vast majority of patients despite of continued transfusion (209.7 ± 159.9 ng/ml and 324.0 ± 289.4 ng/ml per month in MDS and AA, respectively). Over the study period, patients with MDS or AA received a mean of 3.7 and 2.7 units RBC per month, respectively. After 6 months of medication, a slower decrease in the serum ferritin level was observed in MDS patients. In 30 cases, one-year medication of deferasirox was completed. At the end of study (EOS), the serum ferritin levels were significantly decreased to 3,085 ± 2,150 ng/ml (64.4% of baseline level) and 2,913 ± 2,232 ng/ml (69.6% of baseline level, p<0.01) in MDS and AA, respectively. One-year follow-up R2 MRI could be evaluated in 24 cases, and LIC was significantly decreased to the level of 19.3 ± 13.6 mg Fe/g dry weight (67.4% of baseline value, p=0.01). Decrease in the level of LIC at EOS in MDS (64.3% of baseline) was comparable to that in AA cases (68.5% of baseline). The most common drug-related adverse events (AE) were gastrointestinal disturbances, non-progressive increase in serum creatinine, and skin rash. However, AE were transient and mild-to-moderate in severity. Deferasirox was discontinued in 28 (35.4%) cases because of death (7 in MDS and 6 in AA), patient refusal (11 cases), and decrease in the serum ferritin level below 500ng/ml (4 cases). All death was ascribed to disease-related causes including cytopenia in nine (11.4%) and disease progression in one (1.3%). This study clearly shows that deferasirox is effective in reducing LIC and serum ferritin level in transfusional iron overload patients with MDS or AA, even with ongoing transfusion requirement, and well tolerated. Careful assessment of patient’s transfusion requirement will be important in making dose adjustment according to purpose of iron chelation. Data from extension phase of this clinical trial may expand our knowledge about the beneficial effects of deferasirox on prolonging survival and improving quality of life in these patients.

scholarly journals Jadenu Substituting Exjade in Beta Thalassemia Major (BTM) Patients with Iron Overload: Effect on Serum Ferritin Concentration, Liver Iron Content and Biochemical Profiles

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4905-4905 ◽  
Author(s):  
Mohamed A Yassin ◽  
Abdulqadir Nashwan ◽  
Nancy Kassem ◽  
Ashraf Tawfiq Soliman ◽  
Vincenzo De Sanctis ◽  
...  
Keyword(s):  
Side Effects ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Liver Iron ◽  
Ferritin Concentration ◽  
Liver Iron Content ◽  
New Formulation

Abstract Thalassemia major (TM) requires chronic blood transfusions ultimately cause iron overload and subsequently end-organ damage unless corrected. Iron chelation has been proven to decrease organ dysfunction and improve survival in transfusion-dependent β-thalassemia. However, taking iron chelation therapy every day has sometimes been a challenge in patients. Deferasirox is a once-daily, oral iron chelator that developed out of a need for a long-acting chelator. The approved mode of administration requires taking deferasirox on an empty stomach with water, apple juice, or orange juice to limit variation in bioavailability. This required administration schedule might not be palatable for patients. Additionally, approximately one-quarter of patients experience mild to moderate gastrointestinal symptoms, which may pose additional challenges. Jadenu is a new oral formulation of Exjade tablets for oral suspension. While Exjade is a dispersible tablet that must be mixed in liquid and taken on an empty stomach ,Jadnu can be taken in a single step, with or without a light meal, simplifying administration of treatment and allows greater convenience and may be associated with fewer gastrointestinal side effects versus the original formulation. This may significantly improve compliance. In addition, the new formulation may be associated increased bioavailability. Jadenu is 36% more bioavailable than the original formulation, Exjade®. Therefore, to convert from Exjade to Jadenu the dose of Jadenu should be about 30% lower, rounded to the nearest whole tablet. To date, the new formulation of deferasirox has only been evaluated in pharmacokinetic studies in healthy volunteers. No clinical data are available yet in patients taking this formulation. The objective of this study was to compare the effect of Jadenu substituting Exjade on serum Ferritin concentration, liver iron content and biochemical profile in (BTM) patients with iron overload. Patients and Methods: Twelve adult patients with BTM were studied. All patients were on regular packed cell transfusion therapy monthly to keep their Hb not less than 9 g/dl before transfusion. They were on Exjade therapy (30 mg/kg per day) for 5 years or more before changing them to Jadenu therapy (14-28mg/kg/day). We evaluated Serum ferritin and the liver iron (LIC) measured by the Ferriscan method. Investigations included measuring hepatic functions (alanine transferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP) and albumin) , creatinine and fasting blood glucose (FBG) every clinic visit (q 3 months). In addition thyroid function (free T4 (FT4), thyrotropin (TSH), 25 OH vitamin D and PTH levels were measured before and one year after starting Jadenu therapy. Patients were monitored for gastrointestinal and other reported side-effects related to the drugs. All patients were on vitamin D 800 U/day and folic acid 5 mg / day. Paired t student test was used to compare lab results before versus after Jadenu treatment. Linear regression equation was used to investigate possible relation between variables. Results A year after treating patients with Jadenu serum ALT decreased (non-significant) but there was no significant change in circulating concentrations of creatinine, albumin, ALP or FBG. (Table 1) Apart from some gastrointestinal complaints reported in 3 patients that did not require discontinuation of therapy, patients did not have any other side effects. There was a non-significant decrease in LIC and ferritin levels after 1 year of using Jadenu. Thyroid and parathyroid hormone did not change during Jadenu therapy. (Table 2) A positive significant correlation was found between serum ferritin level and LIC measured by ferriscan method. LIC and serum ferritin level were correlated significantly with ALT level ( r = 0.31 and 0.45 respectively, p < 0.05) . No significant correlation was detected between LIC and other biochemical or hormonal levels. This study showed that the use of Jadenu after Exjade was associated with non-significant decrease in liver iron and ALT. There was no change in FBG, creatinine albumin or thyroid function. No side effects required discontinuation of the medicine. Conclusion: Jadenu is more palatable and improve quality of life for patients with BTM, however it was associated with minimal decrease in LIC and ALT level suggesting marginal improvement of iron chelation probably due to easier administration. Disclosures No relevant conflicts of interest to declare.

A Multi-Center, Open Label Study Evaluating the Efficacy of Iron Chelation Therapy with Deferasirox In Transfusional Iron Overload Patients with Myelodysplastic Syndromes or Aplastic Anemia Using Quantitative R2 mri.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1125-1125
Author(s):  
Yoo-Hong Min ◽  
Hyeoung Joon Kim ◽  
Kyoo-Hyung Lee ◽  
Jae Hoon Lee ◽  
Hee-Sook Park ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Myelodysplastic Syndromes ◽  
Serum Ferritin Level ◽  
Chelation Therapy ◽  
Transfusion Requirement ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Dry Weight ◽  
Mean Value

Abstract Abstract 1125 Transfusion-related iron overload and its consequences are emerging challenges in chronically transfused patients with myelodysplastic syndromes (MDS) or aplastic anemia (AA). Measurement of liver iron concentration (LIC) is used as a surrogate for total iron burden to guide chelation therapy in transfusion-dependent patients. Although deferasirox (Exjade®, ICL670) is an oral iron chelation agent that is now widely available for the treatment of transfusional hemosiderosis, the clinical data on its specific benefits of iron chelation, including reduction of LIC, in transfusion-related iron overload patients with MDS or AA has been limited. We have prospectively investigated the efficacy of deferasirox for iron chelation by serial measurement of serum ferritin level and LIC, which is measured in vivo using quantitative tissue proton transverse relaxation rates (R2) magnetic resonance imaging (MRI), in transfusional iron overload patients with MDS or AA. Here we report the interim analysis data. A total of 97 patients with de novo MDS (n = 44) or idiopathic AA (n = 53) showing serum ferritin level over 1,000ng/ml were enrolled from 23 institutes. All patients were regularly transfused and received a mean of 28.6 red blood cells (RBC) units in the year prior to the start of the study. Among MDS cases, 3 (8.3%), 25 (69.4%), and 4 cases (11.1%) were categorized as IPSS low-risk, intermediate-1-risk, and intermediate-2-risk group, respectively. In AA cases, 34 (64.2%) were severe form. Mean value of serum ferritin level in enrolled patients was 3,482.6±436.7 ng/ml in MDS, and 3,904.4±399.2 ng/ml in AA at the time of deferasirox initiation. LIC value was measured using quantitative R2 MRI and FerriScan (Resonance Health, Australia) analysis. Mean value of LIC was 20.8 ± 3.5 mg Fe/g dry weight in MDS and 22.6 ± 2.2 mg Fe/g dry weight in AA. Linear regression analysis indicated a close correlation between serum ferritin level and LIC (r=0.55, p<0.001). Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients. If the serum ferritin falls below 500 ng/ml, treatment was withheld. Over the study period, patients with MDS and AA received a mean of 24.2 and 22.0 units RBC per year, respectively. At the end of study (EOS), the serum ferritin levels were significantly decreased to 3,045.1±446.5 ng/ml and 2,614.7±311.9 ng/ml (p=0.005) in MDS and AA, respectively. One-year follow-up R2 MRI could be evaluated in 55 cases, and at the end of study (EOS), the LIC were significantly decreased to 14.3±2.9 mg Fe/g dry weight (p=0.05) and 15.3±2.3 mg Fe/g dry weight (p=0.001) in MDS and AA, respectively. The most common drug-related adverse events (AE) were gastrointestinal disturbances, non-progressive increase in serum creatinine, and skin rash. However, AE were transient and mild-to-moderate in severity. Deferasirox was discontinued in 30.9% cases because of death, patient refusal, and decrease in the serum ferritin level below 500ng/ml. All death was ascribed to disease-related causes. This study clearly shows that deferasirox is effective in reducing LIC and serum ferritin level in transfusional iron overload patients with MDS or AA, even with ongoing transfusion requirement, and well tolerated. Careful assessment of patient's transfusion requirement will be important in making dose adjustment according to purpose of iron chelation. Data from extension phase of this clinical trial may expand our knowledge about the beneficial effects of deferasirox on prolonging survival and improving quality of life in these patients. Disclosures: No relevant conflicts of interest to declare.

Adults with Severe Sickle Cell Anaemia and Iron Overload Have a High Incidence of Osteopenia and Osteoporosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1684-1684 ◽  
Author(s):  
Farrukh T. Shah ◽  
Ratna Chatterjee ◽  
Matilda Owusu-Asante ◽  
John B. Porter
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Dry Weight ◽  
Iron Chelation Therapy ◽  
Liver Iron

Abstract Background: There is very little published data on osteopenia or osteoporosis in patients with sickle cell disorders (SCD) with only occasional case reports that have noted osteopenia in individual SCD patients. It is known that individuals of Afro-Caribbean decent have on average higher BMD scores then age matched Caucasian controls. The causes for bone demineralisation in SCD may be multifactoral. Putative contributory mechanisms include; marrow expansion, bone infarction, delayed puberty from anaemia, low vitamin D, iron overload from blood transfusion, iron chelation therapy, and hypogonadism. Methods and Findings: 17 consecutive SCD patients who had previously been transfused or were currently on a transfusion programme underwent DEXA scanning using a Hologic QDR 4500A. Hypogonadism was assessed for in all patients as well as Vitamin D3, parathyroid hormone (PTH), serum ferritin and haemoglobin levels. 11 of the 17 patients had undergone MRI to assess liver iron. Of 10 females, 6 had osteopenia (Z >−1.0, n= 4) or osteoporosis ( Z >−2.0, n=2) in the spine compared to age matched caucasian controls (p=0.008). In contrast, only 4 had significant hip demineralisation; 2 patients had osteoporosis and 2 were osteopenic. All patients with hip osteopenia also had spinal osteopenia. Liver iron concentration was significantly higher in the osteopenic (9.4mg/g dry wt) than the non-osteopenic group (1.95mg/g dry wt) (p=0.01). Mean serum oestradiol levels were no different between the osteopenic (235 pmol/L) and the non osteopenic patients (287 pmol/L). No differences in ferritin, units of blood transfused, parathyroid hormone or vitamin D level were seen. Only 2 females had received iron chelation with deferrioxamine one of whom was osteopenic. Among 7 males, 2 had spinal osteopenia (mean Z score −1.4) (p= 0.05) but none had osteopenia of the hip. The liver iron was higher in the osteopenic males (mean 12.9 mg/g dry weight) than in the non osteopenic group (mean 2.32 mg/g/dry weight) (p <0.05). Serum ferritin was also higher in osteopenic patients (mean 3729ug/l) than the non-osteopenic group (mean 745ug/l) (p=0.008). No significant difference between the serum testosterone and units of blood transfused, parathyroid hormone or vitamin D level was seen. Only one of the patients had received iron chelation and he was not osteopenic. Among all patients together, there was no evidence on MRI of increased cardiac iron but there was evidence of hypogonadothrophic hypogonadism is 1 female, while the remainder were not hypogonadal. There was evidence of disturbance of the Calcium- Vitamin D- PTH axis in 2 patients (1 male,1 female) both of whom were osteopenic. Conclusion: Osteopenia is a surprisingly common in adult patients with sickle disorders; 47% of patients had osteopenia. Iron loading may be a relevant contributing factor as liver iron was significantly greater in osteopenic than non-osteopenic patients. Hypogonadism and iron chelation therapy can be reasonably excluded as contributory facors in most patients but should be monitored in all patients on transfusion programmes.

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

Transfusion History, Iron Chelation Practices and Status of Iron Overload across Various Transfusion-Dependent Anemias: Data from the Large- Scale, Prospective, 1-Year EPIC Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3880-3880
Author(s):  
Maria Domenica Cappellini ◽  
Norbert Gattermann ◽  
Vip Viprakasit ◽  
Jong Wook Lee ◽  
John B Porter ◽  
...  
Keyword(s):  
Iron Overload ◽  
Large Scale ◽  
Chelation Therapy ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Dry Weight ◽  
Thalassemia Major ◽  
Liver Iron ◽  
Baseline Characteristics ◽  
Transfusion History

Abstract Background: The prospective, 1-yr multicenter EPIC trial evaluated the efficacy and safety of once-daily oral deferasirox (Exjade®) in more than 1700 patients (pts) with transfusion-dependent anemias. Data were collected from each patient at enrollment, providing an insight into transfusion history, body iron burden, and the nature and success of previous chelation therapy in a large group of pts with iron overload previously treated with chelation therapy. Methods: Enrolled pts were aged ≥2 yrs, had transfusion-dependent anemia and serum ferritin (SF) levels of ≥1000 ng/mL, or <1000 ng/mL with a history of multiple transfusions (>20 transfusions or >100 mL/kg of RBCs) and MRI-assessed liver iron concentration (LIC) >2 mg Fe/g dry weight (dw). Baseline assessments included transfusion history, previous chelation therapy, SF levels and LIC (if carried out) in the previous yr. Results: 1744 pts (901 M, 843 F) were enrolled. Underlying anemias were: thalassemia major (TM; n=937), thalassemia intermedia (TI; n=84), myelodysplastic syndromes (MDS; n=341), aplastic anemia (AA; n=116), sickle cell disease (SCD; n=80), rare anemias (red cell aplasia and anemias mostly hemolytic in nature; n=43), Diamond-Blackfan anemia (DBA; n=14), and various other conditions associated with anemias requiring transfusion (n=129). Baseline characteristics for key underlying anemias are presented in Table 1. Median SF levels were >2500 ng/mL and mean LIC in the previous yr was >7 mg Fe/g dw in all groups (except DBA for SF levels). MDS pts had received the most transfusions in the previous yr, although they had also spent a smaller proportion of their lifetime, and less total time, receiving transfusions than any other cohort. Together with AA pts, the MDS cohort also contained the highest proportion of pts who were chelation-naïve (68% and 48%). SCD pts were the least-transfused group in terms of amount of blood given, but had been receiving transfusions for more than 13 yrs. As expected, TM pts had spent the greatest proportion of their lifetime on transfusions and received the greatest volume of blood per kg in the previous yr. The group labeled by investigators as TI were relatively heavily transfused for this patient population. Table 1. Baseline characteristics for key underlying anemias All (n=1744) TM (n=937) TI (n=84) MDS (n=341) AA (n=116) SCD (n=80) Rare (n=43) DBA (n=14) *Mean ± SD; **Median Age, yrs* 30.6±23.3 18.4±10.8 19.2±14.4 67.9±11.4 33.3±17.1 23.9±13.2 39.5±22.7 17.3±13.2 Transfusions in last yr* 17.8±12.5 17.5±8.8 13.5±7.1 24.3±17.7 12.5±13.0 10.7±8.2 21.0±18.7 19.0±18.7 Total transfused in last yr, mL/kg* 159±136 190±139 155±87 116±123 116±179 84±57 153±142 185±148 Total yrs on transfusions* 12.3±10.4 16.8±10.4 10.2±7.8 3.6±4.6 6.1±5.7 13.0±9.6 10.9±11.8 13.3±10.0 % of lifetime on transfusions* 62.9±39.4 89.8±15.2 61.2±28.8 5.7±8.4 27.1±29.3 59.5±30.1 44.3±41.5 87.5±23.2 LIC in last yr, mg Fe/g dw* 10.7±9.0 9.5±7.8 9.7±5.5 14.4±8.5 12.0±4.3 11.8±8.4 – 8.8±4.2 SF, ng/mL** 3135 3157 3493 2730 3254 3163 3161 2289 Prior chelation, % DFO 58.6 66.7 78.6 40.2 26.7 62.5 55.8 71.4 Deferiprone 1.6 1.3 – 4.1 – 1.3 2.3 – DFO/deferiprone 16.7 25.0 4.8 7.0 5.2 12.5 11.6 14.3 Other 0.3 0.4 – 0.3 – – – – None 23.0 7.0 16.7 48.4 68.1 23.8 30.2 14.3 Conclusions: Data from this study population show that, although most pts with thalassemia, SCD, DBA and rare anemias had received previous chelation therapy, LIC and SF levels were above levels associated with significant negative outcomes (>7 mg Fe/g dw and >2500 ng/mL, respectively), which suggests that previous chelation practices were sub-optimal. Many pts with MDS and AA were chelation-naïve despite being heavily iron overloaded, highlighting that the risks of iron overload are still underestimated. These data highlight the need to carefully monitor iron levels in pts at risk of iron overload and initiate chelation therapy to avoid serious clinical sequelae.

Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up

Blood ◽  
2011 ◽  
Vol 118 (4) ◽  
pp. 884-893 ◽  
Author(s):  
M. Domenica Cappellini ◽  
Mohamed Bejaoui ◽  
Leyla Agaoglu ◽  
Duran Canatan ◽  
Marcello Capra ◽  
...  
Keyword(s):  
Adverse Events ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Dry Weight ◽  
Thalassemia Major ◽  
Efficacy And Safety ◽  
Liver Iron ◽  
Median Serum

Abstract Patients with β-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged ≥ 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received ≥ 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with ≥ 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ± 11.2 mg Fe/g dry weight (dw; n = 103; P < .001) and 3.1 ± 7.9 mg Fe/g dw (n = 68; P < .001) in the deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n = 196; P < .001) and 371 ng/mL (n = 147; P < .001), respectively, after ≥ 4 years' exposure. Investigator-assessed, drug-related adverse events, including increased blood creatinine (11.2%), abdominal pain (9.0%), and nausea (7.4%), were generally mild to moderate, transient, and reduced in frequency over time. No adverse effect was observed on pediatric growth or adolescent sexual development. This first prospective study of long-term deferasirox use in pediatric and adult patients with β-thalassemia suggests treatment for ≤ 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials.gov as #NCT00171210.

scholarly journals LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPY

2014 ◽  
Vol 6 (1) ◽  
pp. e2014025 ◽  
Author(s):  
Ashraf Tawfik Soliman ◽  
Mohamed Yassin ◽  
Fawzia AlYafei ◽  
Lolwa Al-Naimi ◽  
Noora Almarri ◽  
...  
Keyword(s):  
Liver Function ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Negative Correlation ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Growth Potential ◽  
Igf I ◽  
Liver Functions

With regular blood transfusion and iron chelation therapy, most patients with thalassemia major (BTM) now survive beyond the third decade of life . Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are important causes of liver pathology. Iron chelation with desferrioxamine (Desferal)  reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of Deferasirox (Exjade- DFX ), an  oral single dose therapy has improved the compliance to chelation therapy.Aims: To study the long-term liver functions in BMT patients, seronegative for liver infections before versus after DFX therapy in relation to ferritin level and IGF-I level.Methods: Liver function tests including: serum bilirubin, alanine transferase (ALT), aspartate transferase (AST) , albumin, insulin-like growth factor – I (IGF-I) and serum ferritin concentrations were followed every 6 months in 40 patients with BTM, with hepatitis negative screening (checked every year), for at  least   five years of DFO therapy and 4-5 years of DFX therapy .Results: DFX  therapy (20 mg/kg/day)  significantly decreased serum ferritin level in patients with BTM, this was associated with significant decrease in serum ALT, AST, ALP and increase in IGF-I concentrations. Albumin concentrations did not change after DFX treatment. ALT and AST levels were correlated significantly with serum  ferritin concentrations ( r = 0.45 and 0.33 respectively , p < 0.05) . IGF-I concentrations were correlated significantly with serum ALT (r= 0.26, p = 0.05) but not with AST, ALP, bilirubin or albumin levels.The negative correlation between serum ferritin concentrations and ALT suggests that impairment of hepatic function negatively affects IGF-I synthesis in these patients due to iron toxicity, even in the absence of hepatitis.Conclusions: Some impairment of liver function can occur in hepatitis negative BMT patients with iron overload. The use of DFX was associated with mild but significant reduction of ALT, AST and ALP and increase in IGF-I levels. The negative correlation between IGF-I and ALT concentrations suggest that preventing hepatic dysfunction may improve the growth potential in these patients.

Iron Chelation Therapy in Transfusion Dependent Patients with Thalassemia and Minimal Liver Iron Load

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4270-4270
Author(s):  
Antonios Kattamis ◽  
Konstantinos Stokidis ◽  
Theoni Petropoulou ◽  
Dimitra Kyriacopoulou ◽  
Polyxeni Delaporta ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Iron Overload ◽  
Research Funding ◽  
Chelation Therapy ◽  
Combined Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Liver Iron ◽  
Iron Load ◽  
Low Levels

Abstract Abstract 4270 Background: Recent advances in the treatment of iron overload in patients with transfusion- dependent thalassemia have dramatically changed iron related morbidity and mortality. Intensive chelation therapy by using combination therapy or monotherapy at high doses had led to total clearing of the iron in many patients. The best approach for chelation treatment in patients with low levels of iron overload is debatable. Patients and Methods This study included all the patients with thalassemia major with minimal liver iron overload, followed in our unit. More precisely, to be eligible for this observational study, the patients needed to have liver iron concentration (LIC) <1.5 mg Fe/gram dry weight tissue, defined by MRI, and to have at least a subsequent MRI evaluation after this time. The mean observation time, which was the time between the two MRIs, was 16.9±5.2 months. Results Fourty five patients (22 females, 30 non-splemectomized, 21 HCV seropositive, mean age: 31±5.6 years) have reached minimal levels of iron overload in any time point after 2004. Thirty one of them have been treated with combined therapy of desferrioxamine (DFO) and deferiprone (DFP) and 5, 6 and 3 with monotherapy of deferasirox (DFX), DFP and DFO, respectively. After reaching these levels, 42% of the patients changed therapy, with the most frequent change being from combined therapy to monotherapy (15 patients). Baseline ferritin levels at the time of the first MRI range from 43 to 4336 ng/ml (median 230 ng/ml) and they were not affected by spleen, gender or HCV status. Baseline LIC (mean 1.2 ± 1.7 mgFe/g.d.w.) correlated well with ferritin levels (Spearman's rho = 0.47, p<0.005), as did ferritin changes to LIC changes (Spearman's rho = 0.67, p<0.005). The results on the follow up evaluation, stratified according to the actual treatment, are shown in the table Deferiprone was less efficacious in controlling both LIC and ferritin levels compared to combination therapy (p=0.016 and 0.031, respectively). Fifteen out of 17 patients treated with DFP showed an increase in LIC, despite using the recommended dose. Six out of 9 patients treated with DFX, most at a low dose, showed an increase in LIC. There were no differences in changes in the cardiac parameters (LVEF, cardiac T2*) in between treatment groups. The efficiency of DFP and DFX, which represents the ratio of iron excreted to the theoretical maximum of iron that could be bound by the chelators, was calculated at 1.8±0.9 % and 15.2 ± 3.6 %, respectively. Conclusions Current iron chelation therapy regimens are able to render iron load-free many patients with thalassemia major. As iron accumulation from transfusions continues, a fine balance needs to be found in which neither worsening of iron overload nor toxicity from excessive dose of iron chelators will occur. This study showed that at low levels of iron overload both combination therapy and DFX can control iron accumulation, whether monotherapy with DFP may be insufficient to achieve iron balance in many patients. The dose of the chelators needs to be adjusted according to the needs and the clinical course of the patients, which can be predicted by the trend of the ferritin levels. Furthermore, it should be kept in mind that at low levels of iron overload, the iron chelators' efficiency may be lower than previously described. Disclosures: Kattamis: NOVARTIS ONCOLOGY: Honoraria, Research Funding, Speakers Bureau; APOPHARMA: Honoraria. Ladis:NOVARTIS ONCOLOGY: Honoraria, Research Funding; APOPHARMA: Honoraria, Research Funding.

scholarly journals Correlation between serum ferritin level, cardiac and hepatic T2-star MRI in patients with β-thalassemia major in Al-Diwaniya thalassemia center

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Alaa Mutter Jabur Al-Shibany ◽  
AalanHadi AL-Zamili
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Iron Level ◽  
The Mean ◽  
T2 Mri

Patients with transfusion dependent thalassemia major is often associated with iron overload. Proper use of iron chelators to treat iron overload requires an accurate measurement of iron levels. Magnetic resonance T2-star (T2* MRI) is the preferred method to measure iron level in the liver andthe heart. The goal of our study was to see if there is an association exists between serum ferritin level and T2* MRI results in patients with beta thalassemia major.This study was done in Al-Diwaniya Thalassemia center,Maternity and children teaching hospital,Iraq. During the period from 1st of January to 31st of October. Fifty eight patients with a diagnosis of beta thalassemia major were enrolled in the study. They were older than five years old,transfusion dependent and on chelation therapy. Hepatic and Myocardial T2*MRI and the mean serum ferritin levels were measured during the study period for all patients.There is a significant correlation was observed between serum ferritin level and cardiac T2*MRI (p=0.018 ). also a significant correlation was observed between serum ferritin and hepatic T2*MRI (p=0.02). Neither cardiac T2* MRI nor hepatic T2* MRI show any correlation with the mean age.our study also showa positive correlation between the patients withcardiac T2* MRI and the development of diabetes mellitus in contrast to hepatic T2* MRI in which there is no any correlation. Hypothyroidism was observedno correlation with either cardiac or hepatic T2* MRI.Our results showed a positiveassociation between hepatic, cardiac T2*MRI and serum ferritin levels.

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