Deferasirox Is the Only Iron Chelator Acting as a Potent NF-KB Inhibitor in Myelodysplastic Syndromes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2671-2671 ◽  
Author(s):  
Emanuela Messa ◽  
Ilaria Defilippi ◽  
Antonella Roetto ◽  
Francesca Messa ◽  
Francesca Arruga ◽  
...  
Keyword(s):  
Iron Overload ◽  
Cell Lines ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
K562 Cells ◽  
Iron Chelator ◽  
Ros Scavenging ◽  
Transfusion Therapy ◽  
Significant Difference

Abstract Iron overload is a critical issue for low risk myelodisplastic syndrome (MDS) patients with a long tranfusional history and often requires chelation therapy. Iron chelation is as an independent prognostic factor for survival in MDS but can also improve haemoglobin level in some cases with different drugs and modalities. Recently a once daily oral chelator Deferasirox became available for the treatment of secondary hemosiderosis also in MDS patients and it has been described an haemoglobin improvement in a many patients within a few months of treatment. Moreover it was demonstrated that the transcriptional factor NF-kB is abnormally activated in MDS blast cells. Its pathway can be mediated by a broad variety of stimuli, sometimes dependent by reactive oxygen species generated by iron overload but it is activated even in the absence of iron overload. Aim of our study was to compare the effects of the 3 commercially available iron chelators on NF-kB activity in MDS and to identify a possible mechanism responsible for the observed reduced transfusion requirement during iron chelation therapy. We collected 40 PB samples from MDS patients: 18 RA, 14 RAEB, and 8 s-AML. Thirty of them presented hepatic iron overload (measured by SQUID biomagnetic liver susceptometry) and serum ferritin levels over 5000 ng/ml. Ten samples were collected before starting transfusion therapy. MNC cells were incubated with 50 microM Deferasirox for 3 hrs. K562 and HL60 cells were analyzed as controls and were incubated with Deferasirox 50 mM, Deferiprone 0,3 mM and Deferioxamine 0,3 mM for 18 hours and with the DL-Dithiothreitol (DTT) 100 mM for 18 hours as control. NF-kB activity was evaluated using both EMSA and ELISA methods. Apoptosis was evaluated by FACS for the detection of annexin V. Deferasirox incubation induced a significant decrease of NF-kB activity both in HL60 and K562 cells lines (EMSA method). We detected an increased activation of NF-kB as compared to healthy subjects in 6 RA, 12 RAEB, in all the s-AML PB samples and in cell lines. No significant difference was detected in NF-kB activity by comparing patients with or without iron overload (p=0,5). The percentage of samples presenting NF-kB activity increases during disease progression being higher in RAEB and s-AML as compared to RA (p=0,003). Among patients with increased NF-kB (n=14) the incubation with Deferasirox induced a significant reduction of NF-kB activity (p=0,0002). The degree of NF-kB inhibition was not significantly different according to the level of iron overload. Apoptosis was not significantly triggered by incubation with any of the different chelators. HL60 and K562 cells incubation with the Deferiprone and Deferioxamine failed to induce a significant reduction of NF-kB activity. NF-kB is abnormally activated in MDS patients and this activity is not strictly related to iron overload being present in patients with normal serum ferritin levels and in cell lines. Deferasirox is the only commercially available iron chelator acting as a potent NF-kB inhibitor and this effect is not shared by Deferioxamine, Deferiprone or DTT. This behaviour suggests that it is independent from ROS scavenging that is a common feature of all the mentioned drugs. Our in vitro observation could be an explanation for the early improvement of hemoglobin levels observed in some patients under deferasirox chelation that seems not related to a sharp decrease of iron overload.

Effective and Safe Deferasirox Treatment of Patients with Various anemia's and Transfusional Iron-Overload in the Medical Practice: Results From Two German Observational Studies

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5165-5165
Author(s):  
Christian Junghanss ◽  
Rudolf Schlag ◽  
Bernd Gaede ◽  
Matthias Moelle ◽  
Steffen Doerfel ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Observational Studies ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Beta Thalassemia ◽  
Final Visit ◽  
Iron Chelation Therapy ◽  
The Mean

Abstract Abstract 5165 Background: Progressive anaemia is highly prevalent amongst many malignant diseases leading to RBC transfusion-dependency. Therefore transfusion-related iron overload (IOL) is common in these patients (pts) and can result in multiple organ failure. Iron chelation therapy prevents organ failure, reduces the risk of infections and can improve hematopoesis in some diseases. The once-daily oral iron chelator deferasirox has been shown to reduce iron overload in pts with various transfusion-dependent anaemias assessed by serum ferritin (SF). Despite extensive knowledge of iron chelation in MDS or beta-thalassemia pts, data in pts with other anaemias is limited. Here, we present data from a subgroup of transfusion-related IOL pts that were included two non-interventional studies (EXTEND, EXJANGE) performed in Germany and who suffered from diseases other than MDS or beta thalassemia. Methods: 130 pts with various malignant diseases such as myeloproliferative disorders (43 pts, including 31 pts particular specified as myelofibrosis), acute myeloid leukaemia (14 pts), sickle cell anaemia (6 pts), aplastic anaemia (11), congenital aplastic anaemia (5) or Non-Hodgkin's lymphoma (6 pts) were treated with deferasirox in the daily-routine setting of office-based physicians and included in either the EXTEND or EXJANGE study. Patient with MDS or beta-thalassemia were also included in the studies, but are excluded from this analysis. Analysis is based on 1-year pooled data of these two, multicenter, non-interventional observational studies. Transfusion-dependent pts with IOL with or without prior chelation were enrolled and received the iron chelator deferasirox. Prescription of deferasirox, just as inclusion and exclusion criteria was in accordance with the terms of Exjade marketing authorization in the EU. Efficacy and safety parameters, including serum ferritin and adverse events (AEs), were collected in 2-monthly intervals. Results: 98 pts had no prior chelation therapy (51 M, 45 F, 2 missing; mean age 63.3, range 3.2–91.9 yrs) and a median baseline SF of 2,968 (range 561–11, 423) ng/mL. 32 pts had prior received prior chelation therapy (mainly with desferal; 17 M, 15 F; mean age 50.1, range 3.5–80.9 yrs) and a median baseline SF of 2,635 (range 539–19, 540) ng/mL. The mean number of prior red blood cell transfusions was 55. The mean prescribed daily dose of deferasirox at the first visit was 16.3 mg/kg/d rising up to 18.1 mg/kg/d after 12 months. During treatment, median SF levels clearly decreased from first to final visit [-806 ng/mL; p<0.0001 (explorative analysis)] in the chelation-naïve and also in the pre-chelated population [-300 ng/ml; p = 0.1705 (explorative analysis)]. The median observation period and days on therapy was 349 and 343 days, respectively. At final visit 74 pts (56.9%) were still on deferasirox therapy. Reasons for discontinuation by the final visit included 19 AEs (35.2%). 45 pts (34.6%) experienced an investigator assessed drug-related AE. The most common drug-related AEs were diarrhea (n=17; 37.8%), nausea (n=11; 24.4%) and blood creatinine increased (n=6; 13.3%). As in previous clinical trials, serum creatinine clearances showed a minor decrease over the study period (median decrease until final visit: 4 ml/min). Conclusion: Our analysis confirmed that deferasirox is effective and well tolerated in chelation-naïve as well as in previously chelated pts with transfusion-related IOL and diseases other than MDS or beta thalassemia. As baseline serum ferritin values were >2,500 ng/mL even in pts with prior chelation therapy, adequate chelation treatment should be considered earlier at a serum ferritin >1,000 ng/mL in pts with transfusion-dependent IOL for adequate iron chelation therapy. Disclosures: Junghanss: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Haus:Novartis Pharma: Employment. Junkes:Novartis: Employment. Leismann:Novartis: Employment.

Iron Chelation Therapy with Deferasirox (Exjade®, ICL670) or Deferoxamine Is Effective in Reducing Iron Overload in Patients with Advanced Fibrosis and Cirrhosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2696-2696 ◽  
Author(s):  
E. Angelucci ◽  
B. Turlin ◽  
D. Canatan ◽  
A. Mangiagli ◽  
V. De Sanctis ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Advanced Fibrosis ◽  
Liver Iron ◽  
Once Daily ◽  
Tissue Iron

Abstract Introduction: Although the direct measurement of iron from a liver biopsy is the reference standard method to determine liver iron concentration (LIC), results are highly unreliable in patients with advanced fibrosis and cirrhosis. As a result, chelation therapy is difficult to monitor in this patient population where effective chelation therapy may be critical. It is therefore important to assess parameters additional to LIC in order to accurately assess body iron in these patients. Aim: To analyze the efficacy of chelation with deferoxamine (DFO) and the investigational once-daily, oral iron chelator deferasirox (DSX) in patients with advanced fibrosis participating in DSX registration studies. Methods: A subgroup of patients from DSX Studies 0107 and 0108 were selected based on a staging result according to the Ischak scale of 5 (incomplete cirrhosis) or 6 (probable or definite cirrhosis), measured either at baseline or after 1 year of chelation therapy. The subgroup of patients with β-thalassemia participating in Study 0107 received DSX (n=26) or DFO (n=30). In Study 0108, the subgroup of patients with β-thalassemia unable to be treated with DFO (n=12) or patients with anemias other than β-thalassemia (n=7) were treated with DSX only. In both studies, patients received chelation therapy according to baseline LIC. Results: In Study 0107, treatment with DSX or DFO led to a decrease in semi-quantitative tissue iron score (TIS) and LIC, which were paralleled by changes in serum ferritin. TIS, LIC and serum ferritin in a subgroup of patients with advanced fibrosis and cirrhosis treated with DSX and DFO (Study 0107) TIS LIC, mg Fe/g dw Serum ferritin, ng/mL DSX (n=26) DFO (n=30) DSX (n=26) DFO (n=30) DSX (n=26) DFO (n=30) *Median (min, max) Baseline* 35.5 (4,39) 34 (10,52) 25.5 (2.4,45.9) 19.5 (3.9,55.1) 4195 (321,12646) 4144 (653,15283) Change from baseline* −2 (−43,20) −2 (−25,16) −9.4 (−42.2,13.1) −3.1 (−24.5,12.4) −1269 (−7082,3609) −951 (−8259,1264 Similarly, in Study 0108, DSX treatment produced a decrease in all 3 parameters in patients with β-thalassemia or rare anemia. TIS, LIC and serum ferritin in a subgroup of β-thalassemia and rare anemia patients with advanced fibrosis and cirrhosis (Study 0108) TIS LIC, mg Fe/g dw Serum ferritin, ng/mL β-thalassemia (n=12) Rare anemia (n=7) β-thalassemia (n=12) Rare anemia (n=7) -thalassemia β (n=12) Rare anemia (n=7) *Median (min, max) Baseline* 35 (4,48) 41 (32,49) 29.4 (3.8,37.4) 26.3 (15,51.3) 4813 (440,11698) 2385 (1553,9099) Change from baseline* 2 (−19,27) −3 (−20,1) −1.6 (−18,9.9) −10 (−13.9,8.8) −986 (−4453,2131) −1322 (−2609,1901) Conclusions: Chelation therapy with DSX or DFO is effective in reducing iron overload in patients with advanced fibrosis and cirrhosis. The trends observed in TIS and LIC were closely mirrored by changes in serum ferritin, highlighting the validity of this method for monitoring chelation therapy in this population.

Clinical-Reported Outcomes Of Deferoxamine Versus Deferasirox In The Treatment Of Homozygous BetaThalassemia

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Zeina A Munim Al-Thanoon ◽  
Zeina A Munim Al-Thanoon ◽  
Mustafa Basil ◽  
Nasih A Al-Kazzaz
Keyword(s):  
Serum Ferritin ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Beta Thalassemia ◽  
Control Group ◽  
Current Standard ◽  
Cross Sectional ◽  
Significant Difference ◽  
Multiple Blood ◽  
Group 2

Iron chelation therapy with deferoxamine (DFO),the current standard for the treatment of iron overload in patients with betathalassemia,requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence,resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox (DFX) is an orally administered iron chelator that has been approved for use in many countries. The requirement of an effective,well tolerated iron chelator with a less demanding mode of administration has led to the development of deferasirox. The present study was aimed to compare the satisfaction and compliance with deferoxamine versus deferasirox (Exjade®),a novel oral iron chelator in patients with transfusion - dependent beta- thalassemia. A cross-sectional,single-center investigation study was carried out in the Thalassemia Center of Ibn-Atheer Teaching Hospital in Nineveh province,Iraq. One hundred and eight thalassemic patients aged between 2- 20 years old having received multiple blood transfusions and a serum ferritin greater than 1500 ng/ml. Patients were randomised into two groups. Group 1 received deferoxamine at a dose of 20-50mg/kg/day and group 2 received deferasirox at the dose of 10-30 mg/kg/day. Another 56 apparently healthy volunteers were used as a control group. The assessment of chelation was done during the period between November 2013 and February 2014 by measurement of serum ferritin. Satisfaction and compliance was assessed by using a special questionnaire prepared by the researcher. Out of the 108 thalassemic patients enrolled there was no discontinuation in treatment with the two drugs under study. The serum ferritin did not change significantly in any of the chelation groups. In comparison with the patients who were treated with DFO,those receiving DFX reported a significantly higher rate of compliance and satisfaction (P < 0.05). However,no significant difference was observed between the two groups regarding their satisfaction (P > 0.05).Compliance with deferasirox (50 %) was more than that with deferoxamine (20 %). Satisfaction with deferoxamine was significantly lower than deferasirox (p= 0.00).

Estimating Iron Burden in Simple Vs. Modified Manual Exchange Transfusions in Pediatric Sickle Cell Patients on Chronic Transfusions

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4850-4850
Author(s):  
Mansi Lalwani ◽  
Mary DeBarr ◽  
Ann O'Riordan Mary ◽  
Connie M Piccone ◽  
Brian W Berman
Keyword(s):  
Iron Overload ◽  
Sickle Cell ◽  
Exchange Transfusion ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Red Cell ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Packed Red Blood Cells ◽  
Transfusion Protocol

Abstract Abstract 4850 Introduction: Nearly 100,000 Americans are affected by sickle cell disease (SCD), making it one of the most prevalent genetic disorders in the United States. Individuals with SCD exhibit significant morbidity and mortality related to chronic hemolysis, vasculopathy, and vascular occlusion by red cell sickling. Currently, red cell transfusions are a primary therapy for some of the acute and chronic complications of SCD, including prevention and treatment of stroke. The benefits of transfusion therapy are well known; however, transfusional iron overload is an inevitable consequence. Excess iron in the circulation leads to the formation of reactive oxygen species which ultimately causes end-organ damage. It is well established that adult SCD patients with significant iron overload have a higher mortality. As a result, exchange transfusion protocols are utilized to try to decrease overall iron overload. In our center, a modified manual exchange (MME) protocol is used which involves therapeutic phlebotomy of approximately 5–7.5ml/kg followed by the infusion of 15–20ml/kg packed red blood cells. MME is performed in the outpatient setting every 4–6 weeks with a goal hemoglobin S of less than 30%. Objective: The primary objective of our study was to describe the benefits of a MME protocol compared with a simple transfusion protocol in patients experiencing both. The effects of MME versus simple tranfusion on systemic iron overload were evaluated using serum ferritin levels, net transfusion volume, and need for iron chelation therapy. Study Design/Methods: A retrospective chart review was performed on patients with SCD (type SS) less than 18 years of age who were on chronic transfusions and transitioned from a simple to a MME protocol. All patients included were on chronic transfusions for primary/secondary stroke prevention. Exclusion criteria included all patients on automated exchange transfusion protocols and those patients who started iron chelation therapy after January 1, 2008. Demographic as well as clinical and laboratory data were collected on each patient. A simple transfusion was defined as 20ml/kg packed red blood cells transfused every 4–6 weeks. The MME protocol was defined as above. Iron overload was assessed using indicators including net volume of blood transfused, serum ferritin, and the need for iron chelation during both time periods, and differences were calculated. The Wilcoxon signed rank test was used for the change in amount of blood transfused. Slopes of ferritin levels over time were estimated for each transfusion protocol separately using mixed model methods. The need for chelation therapy was tabulated for each patient. Results: A total of six patients were included in the study, 4 boys and 2 girls. Ages ranged from 6–14 years. Four patients had been on chronic transfusions for more than 2 years prior to the start of our study. The mean net volume transfused during simple transfusion and MME was 400ml and 290ml, respectively (p=0.03). The slope of ferritin rise was 0.18 (CI: 0.11, 0.84) for MME and 1.37 (CI: 0.56, 2.17) for simple transfusion. One patient was taken off chelation therapy completely after transitioning to MME and another patient was maintained on low-dose chelation while on MME. Conclusions: MME appears to reduce the amount of blood transfused, slow the rise of ferritin, and potentially reduce the need for additional medication. MME may provide a safe and cost effective approach for delaying or preventing iron overload in patients with sickle cell disease who require long term transfusion therapy. Disclosures: No relevant conflicts of interest to declare.

Transfusion-Related Iron Overload: A Covert Risk Of Supportive Cancer Care

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3656-3656
Author(s):  
Anushka Jaffer ◽  
Rebecca Barty ◽  
Erin Jamula ◽  
Grace Wang ◽  
Yang Liu ◽  
...  
Keyword(s):  
Iron Overload ◽  
Cancer Patients ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Adult Patients ◽  
Iron Chelation Therapy ◽  
Not Given ◽  
Screening Practices ◽  
Rbc Transfusion

Abstract Background Chronic transfusion support plays a key role in survival and quality of life for patients with hematological disorders. However, transfusion-related iron overload (TRIO) is a significant cause of morbidity and mortality in these patients.Adequate iron overload (IO) screening and use of iron chelators, if necessary, is now standard practice in chronically transfused individuals such as hemoglobinopathy patients. Screening practices for IO for patients receiving multiple red blood cell (RBC) transfusions for other reasons (e.g. cancer) are unknown. Objective This two part study aimed to detect pediatric (Jaffer et al., 2012) and adult populations at risk for TRIO and to evaluate and compare current screening practices. Methods Children (≤ 18 years) and adults (> 18 years) receiving at least 1 RBC transfusion from January 1, 2008 to December 31, 2011 at a tertiary care academic institution were identified using a transfusion registry database. Only those receiving chronic RBC transfusions were included in the study. Chronic transfusion was defined as ≥20 units of RBC or ≥ 20 RBC transfusions dosed at 15ml/kg within 12 consecutive months where transfusions were not given in the setting of an operating room, trauma or surgical procedures, not given 7 days prior/post-surgical procedures and not all given in one day. An adjudicator resolved study inclusion ambiguity. The analysis excluded hemoglobinopathy patients. Medical records were reviewed to collect patient demographics, diagnosis, and to evaluate IO screening practices and frequency of iron chelation therapy. Results A total of 343 patients met the eligibility criteria: 27 pediatric and 316 adult patients, with mean ages of 8.1 years (SD 5.7) and 62 years (SD 12.6), respectively. Table 1 summarizes demographics, number of transfusions, and IO screening and results. Ferritin levels were checked for 12 (44%) pediatric and 227 (72%) adult patients: 2 (17%) pediatric and 30 (13%) adult patients had values<500 μg indicating no further TRIO screening was required. In the pediatric population, 81% had a cancer diagnosis, and just under a third were tested for ferritin, whereas 64% of the adults had cancer, with nearly two-thirds tested for ferritin. A statistically significant difference was observed in the percentage of pediatric and adult cancer patients screened for IO. Of those cancer patients screened, ferritin level > 500 occurred in 71% of pediatric and 85% of adult patients, with an iron chelator reported in 1 adult. Total RBC transfusions ranged from 20 to 44 with a median of 26.5 for pediatrics and 20 to 176 with a median of 31 for adults. Conclusion Despite high rates of RBC transfusion, screening for TRIO was inconsistent. Although information regarding reasons for not screening for TRIO or not treating with chelation therapy was not collected, the possibilities include a lack of awareness of the risk of TRIO and lack of access to ferriscan and/or to oral iron chelator in Canada for conditions other than hemoglobinopathy and a select subset of MDS cases. Considering TRIO presents an additional, yet unidentified, co-morbidity of cancer therapy and that the therapy (e.g. anthracyclines) may potentiate the end organ effect of TRIO, it is vital to develop strategies to evaluate cancer patients at risk for TRIO and ensure they have access to appropriate iron chelation therapy. Research is needed to explore the comorbidities associated with failure to treat TRIO and to identify barriers to treatment so cancer patients can receive optimal care. Disclosures: Leber: Novartis Canada: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Heddle:Canadian Blood Services and Health Canada: Research Funding.

scholarly journals Estimation of serum ferritin and TSH levels in thalassemia patients undergoing iron chelation therapy

2021 ◽  
Vol 20 (1) ◽  
pp. 130-135
Author(s):  
Soma Ghosh ◽  
Dwaipayan Chakrabarti
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Medical Science ◽  
Iron Chelation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pearson Coefficient ◽  
Heterogenous Group ◽  
Serum Tsh ◽  
Tsh Levels

Objectives & introduction: Thalassemia, heterogenous group of disorders of haemoglobin,characterised by reduced or absent production of one or more of globin chains.Regular redcell transfusion with chelation therapy for iron overload are cornerstones of therapy for ßthalassemia major. Serum ferritin assay is widely available, relatively inexpensive methodfor assessing body iron burden and monitoring response to chelation process which in turnalso improves TSH levels in thalassemic subjects .The objective of this study was to assessprechelation and postchelation levels of serum ferritin and TSH and correlating post chelationlevels of serum ferritin and TSH in thalassemic patients >6yrs undergoing chelation therapy. Materials & methods: Serum TSH measured by Enzyme linked fluorescent assay and serumferritin measured by enzyme linked immunosorbent assay. Results: Amongst 500 participants,47% were males & 53% females. Mean age was 9.04 yrs ;prechelation ferritin and TSH levelswere 2995.78ng/ml with SD of 802.53 and 5.07 μU/ml with SD of 2.52. The postchelationferritin and TSH levels were 2168.80 ng/ml with SD of 1335.89 and 4.51μU/ml with SD of4.76. Paired t test with respect to pre and postchelation ferritin and TSH levels showed 2 tailed pas 0.000 and t>3, both of which considered significant. While correlating post chelation ferritinwith TSH levels; they showed a linear correlation ( Pearson coefficient of .836). Conclusion:Serum ferritin and TSH estimation in prechelation and postchelation periods give an estimateof iron overload with effect of chelation on it. Both levels decrease post chelation presenting alinear correlation between the two. Bangladesh Journal of Medical Science Vol.20(1) 2021 p.130-135

scholarly journals EFFECT OF IRON OVERLOAD AND IRON CHELATORS ON ANTI-MÜLLERIAN HORMONE LEVEL IN EGYPTIAN FEMALE PATIENTS WITH TRANSFUSION DEPENDENT β-THALASSEMIA

2017 ◽  
Vol 10 (4) ◽  
pp. 263
Author(s):  
Noha Sayed Hamed
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Chelation ◽  
Significant Negative Correlation ◽  
Thalassemia Major ◽  
Iron Chelator ◽  
Female Patients ◽  
Excess Iron ◽  
Thalassemia Minor ◽  
Iron Chelator Deferoxamine

Objective: This work aims to determine the effect of iron overload on serum anti-müllerian hormone (AMH) levels in females subjected to transfusion-dependent β-thalassemia by measuring serum ferritin and to investigate the effects of iron chelation therapy including oral deferiprone and subcutaneous deferoxamine in the management of transfusion-related iron overload together with reproductive function.Methods: 90 female patients with thalassemia major (TM), thalassemia intermedia (TI) and thalassemia minor (T minor) were selected to investigate AMH by ELISA and ferritin by IRMA.Results: Serum AMH level was lower in female patients with transfusion dependent β-thalassemia than in T minor also, Ferritin was 25 fold more in TM compared to T minor (3088.0±2497.6 ng/ml vs. 120.3±36.2 ng/ml). There was significant negative correlation of AMH with ferritin in TM (r =-0.949; P<0.001*), in TI (r =-0.378; P =0.039*) and in T minor (r =-0.754; P<0.001*). The iron chelator, deferoxamine had significantly higher ferritin and lower AMH in TM and TI than deferiprone.Conclusion: the results demonstrated that females with TM and TI were found to have lower serum AMH levels than T minor and inversely related to the serum ferritin levels in all thalassemic groups. Also, it demonstrated that deferiprone was more efficient than deferoxamine in removing excess iron and reduced the deleterious effect of excess iron to the reproductive system, which leads to fertility preservation of female patients with transfusion–dependent β-thalassemia.Keywords: Anti-müllerian hormone, Ferritin, Iron overload, β-thalassemia, Deferoxamine, Deferiprone.

scholarly journals A case of transfusion independence in a patient with myelodysplastic syndrome using deferasirox, sustained for two years after stopping therapy

2015 ◽  
Vol 22 (2) ◽  
pp. 128 ◽  
Author(s):  
D. Sanford ◽  
C.C. Hsia
Keyword(s):  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Red Blood Cell Transfusion ◽  
Transfusion Independence ◽  
Clinical Complications ◽  
Increased Risk ◽  
History Of

Patients with myelodysplastic syndrome (mds) experience clinical complications related to progressive marrow failure and have an increased risk of developing acute myeloid leukemia. Frequent red blood cell transfusion can lead to clinical iron overload and is associated with decreased survival in mds patients. Iron chelation therapy reduces markers of iron overload and prevents end-organ damage.Here, we present the case of a patient with lowrisk mds with transfusional iron overload. He was treated for 2 years with an oral iron chelator, deferasirox, and after 12 months of treatment, he experienced a hemoglobin increase of more than 50 g/L, becoming transfusion-independent. He has remained transfusion-independent, with a normal hemoglobin level, for more than 2 years since stopping chelation therapy. Hematologic and erythroid responses have previously been reported in mds patients treated with iron chelation. The durability of our patient’sresponse suggests that iron chelation might alter the natural history of mds in some patients.

Deferasirox (Exjade®, ICL670) Treatment of Inadequately Chelated β-Thalassemia Patients from the Middle East: The ESCALATOR Trial.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3840-3840 ◽  
Author(s):  
Ali Taher ◽  
Amal El-Beshlawy ◽  
Abdullah Al Jefri ◽  
Mohsen El Alfy ◽  
Kusai Al Zir ◽  
...  
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Concentration ◽  
Iron Chelator ◽  
Oral Iron ◽  
Study Cohort ◽  
Liver Iron ◽  
Transfusion Therapy ◽  
Once Daily ◽  
Oral Iron Chelator

Abstract Iron overload is a potentially life-threatening consequence of multiple blood transfusions. Effective iron chelation therapy reduces morbidity and saves lives. Many patients are unable to comply with current treatments, deferoxamine (DFO) or deferiprone (L1), because they cannot tolerate the parenteral infusion regimen required for DFO, because of adverse events (AEs), or because they do not respond to treatment. The objective of the ESCALATOR trial is to evaluate the effectiveness of deferasirox, an investigational once-daily oral iron chelator in advanced clinical development, in reducing liver iron concentration (LIC) in patients with β-thalassemia unable to be properly treated with DFO and/or L1. During a 1-year treatment period, patients will receive deferasirox at a daily dose of 20 mg/kg. Reduction of LIC is the primary endpoint, as assessed by biopsy at baseline and study end. Secondary efficacy variables include serum ferritin (SF) and other potential surrogate markers of iron overload such as concentration of labile plasma iron (LPI) in a subgroup of patients. Safety assessments include AEs and comprehensive laboratory evaluations. To date, 232 patients have initiated treatment at seven centers in five countries (Egypt, Saudi Arabia, Lebanon, Oman, Syria). Demographics, relevant medical history and baseline iron burden parameters are described in the table. Importantly, baseline SF values were significantly correlated with LIC (R=0.63; P&lt;0.0001). The last patient’s last visit will be in June 2006. Age 2 to &lt;16 years (n=159) Age ≥16 years (n=73) All patients (n=232) Mean ± SD; †n=14 Female:male, n 79:80 35:38 114:118 Race (caucasian:oriental:other), n 59:81:19 11:41:21 70:122:40 BMI*, kg/m2 17.4 ± 2.6 21.6 ± 3.2 18.7 ± 3.4 Weight*, kg 29.4 ± 9.9 54.7 ± 9.7 37.3 ± 15.3 Hepatitis B or C, n 43 29 72 Splenectomy, n 46 53 99 Transfusions in previous year*, n 15.5 ± 4.5 14.3 ± 3.7 15.1 ± 4.3 Total volume transfused in previous year*, mL 5265 ± 2469 7446 ± 2953 5873 ± 2784 Years on chelation therapy*, n 6.2 ± 3.5 12.7 ± 4.8 8.2 ± 4.9 Proportion of life on transfusion therapy*, % 89.3 ± 13.9 89.0 ± 14.1 89.2 ± 14.0 Liver pathology grading (modified HAI scale)     Grade 0–6 143 64 207     Grade 7–12 4 0 4     Grade 13–18 0 0 0 LIC, mg Fe/g dw     Mean ± SD 17.1 ± 8.5 20.0 ± 10.0 18.0 ± 9.1     Median (min, max) 16.6 (2.9, 38.2) 19.0 (2.9, 48.9) 17.5 (2.9, 48.9) SF, ng/mL     Mean ± SD 3957 ± 2342 4564 ± 4117 4148 ± 3019     Median (min, max) 3356 (914, 13539) 3335 (956, 23017) 3346 (914, 23017) LPI†,μmol/L     Mean ± SD - - 1.03 ± 0.80     Median (min, max) - - 0.82 (0, 2.65) The ESCALATOR study cohort is a highly challenging population with varied chelation response and transfusion history. The magnitude of LIC and SF, which were well correlated, reflects the severity of iron overload in patients unable to maintain adequate chelation using DFO or L1. This study will provide important insights into the clinical management of iron overload with the well tolerated, once-daily oral iron chelator deferasirox in this difficult-to-treat population.

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

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