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

Author(s):  
Zeina A Munim Al-Thanoon ◽  
Zeina A Munim Al-Thanoon ◽  
Mustafa Basil ◽  
Nasih A Al-Kazzaz

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).

2013 ◽  
Vol 5 (1) ◽  
pp. e2013065 ◽  
Author(s):  
Adel Abd elhaleim Hagag

abstractBackground: Beta thalassemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia requiring life-long blood transfusion that cause iron overload. Silymarin plays a role as oral iron chelator and hepatoprotective agents in thalassemic patients.The aim of this work was to determine silymarin value as an iron chelator in thalassemic patients with iron overload.Patients and Methods: This study was conducted on 40 children with beta thalassemia major under follow-up at Hematology Unit, Pediatric Department, Tanta University Hospital having serum ferritin level more than 1000 ng/ml and was divided in two groups. Group IA: Received oral Deferasirox (Exjade) and silymarin for 6 months. Group IB: Received oral Deferasirox (Exjade) and placebo for 6 months and 20 healthy children serving as a control group in the period between April 2011 and August 2012 and was performed after approval from research ethical committee center in Tanta University Hospital and obtaining an informed written parental consent from all participants in this research. Results: Serum ferritin levels were markedly decreased in group IA cases compared with group IB (P= 0.001). Conclusion: From this study we concluded that, silymarin in combination with Exjade can be safely used in treatment of iron-loaded thalassemic patients as it showed good iron chelation with no sign of toxicity. Recommendations: Extensive multicenter studies in large number of patients with longer duration of follow up and more advanced methods of assessment of iron status is recommended to clarify the exact role of silymarin in reduction of iron over load in children with beta thalassemia.  


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5165-5165
Author(s):  
Christian Junghanss ◽  
Rudolf Schlag ◽  
Bernd Gaede ◽  
Matthias Moelle ◽  
Steffen Doerfel ◽  
...  

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.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5306-5306
Author(s):  
Efthimia Vlachaki ◽  
Vasileios Perifanis ◽  
Antonia Kondou ◽  
Nikolaos Neokleous ◽  
Aikaterini Teli ◽  
...  

Abstract Abstract 5306 Serum uric acid of patients with beta-thalassemia major (b-MA), despite the hyperuricosuria observed in these patients, is usually in the upper normal levels or increased due to excessive catabolism of the red blood cells (ineffective erythropoiesis). Deferasirox a new oral iron chelator with potential nephrotoxicity is recently used as iron overload treatment in patients with b-MA. Aim: Aim of the study is to investigate the effect of deferasirox on uric acid levels of patients with homozygous b-MA. Material-Method: 53 patients were enrolled to the present study with b-MA major, (aged 22.4 ± 14.7 years, range 4–12 years) 36 adults and 17 children, 32 females and 21 male. All the patients were transfusion-dependent with pretransfusional haemoglobin 9gr/dl and treated with iron chelation. The comparison was made between two different time points' measurements of uric acid and ferritin, at the beginning before Deferasirox, and one year later. The blood was taken from the patients early at mornings before the transfusion. Also uric acid was measured in 24 hour urine of patients under deferasirox, or other iron chelation therapy or after weekly discontinuation of deferasirox. Patients taken allopurinol or thiazide or with abnormal kidney function were excluded. Results: There is statistically significant difference (p< 0.001) between the mean annual value of serum uric acid (before 5.2 ± 1.3mg/dl) and ferritin (before 1653,4 ± 1026,3 ng/dl) before and after the start of deferasirox (uric acid after 4.2 ± 1.3 mg/dl and ferritin after 1529,07 ± 1137,44 ng/dl). Also, statistically significant positive correlation between the levels of serum uric acid and ferritin was found during the treatment with deferasirox. However, comparing the uric acid in urine of patients, it was not reported any statistically significant difference between treatment with deferasirox (859,75 ± 122), other iron chelators or without iron chelation for one week (844,32 ± 146). Conclusion: The mechanism of uric acid reduction in patients with b-MA major treated with deferasirox is not clear. However, it does not seem to be associated with excess of excretion by urine. The positive correlation between uric acid level and ferritin, allow us to consider uric acid as a predictor factor of the response to deferasirox therapy. Disclosures: Vlachaki: Novartis Hellas S.A.C.I.: Research Funding. Oikonomou:Novartis Hellas S.A.C.I.: Research Funding.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wasim Muhammad ◽  
Muhammad Ishaq ◽  
Muhammad J. Khan ◽  
Umair Ahmad ◽  
Muhammad Waseem

The main objective of the current study is to evaluate the level and overload of serum ferritin in multi-transfused beta Thalassemia major patients. There is an earnest need to defend the chelation treatment and to make mindfulness about the results of serum ferritin in the patients beta Thalassemia major. This is a Cross sectional analytical study performed in Fatimid foundation Hayatabad, Peshawar, Khyber Pakhtunkhwa province of Pakistan. Those patients who has beta thalassemia major are included in this study. In this study there are total 108 patients in which 54 males and 54 females. The highest mean of serum ferritin level in the category of male was in the age of 12 years were finds 8160.5 ng/mL. Among the female the highest mean of ferritin level was in the age of 17 years were finds 13,349.5 ng/mL. In this study majority of patient’s revealed much high levels of serum ferritin. These levels reveal insufficient chelation. Appropriate chelation of iron load can improve the quality of the life of these patients. The low level of education, Poverty problems, and insufficient health care facility of are the main obstacle in the effective management of ferritin overload in thalassemia patients.


2019 ◽  
Vol 59 (3) ◽  
pp. 144-9
Author(s):  
Hervita Yeni ◽  
Finny Fitry Yani ◽  
Amirah Zatil Izzah ◽  
Gustina Lubis

Background In thalassemia patients, reduced zinc absorption results from increased serum iron due to repeated blood transfusions, increased iron absorption due to ineffective erythropoiesis, and competitive inhibition between iron and zinc in binding to transferrin, a means of transporting both types of minerals in the blood. Few studies have been done to examine zinc levels in thalassemia patients and its relationship with ferritin. Objective To compare serum zinc in thalassemia patients and healthy controls and to assess for a possible correlation between serum ferritin and zinc in thalassemia patients. Methods This cross-sectional study in 68 subjects was done from October 2016 to August 2017. Serum ferritin measured by chemiluminescence immunoassay and serum zinc by inductively coupled plasma mass  spectrometry (ICP-MS). Wilcoxon test was used to analyze for differences between serum zinc in thalassemia patients and controls. Spearman’s correlation test was used to analyze for a possible correlation between ferritin and serum zinc in thalassemia patients. Results There were 34 patients with thalassemia and 34 healthy control subjects. The median serum zinc was 119.34 µg/dL (IQR=71.27) in the thalassemia group and 120.08 µg/dL (IQR=26.28) in the control group (P=0.36). There was no significant correlation between serum ferritin and zinc in thalassemic children (r=-0.023; P=0.895). Conclusion There is no significant difference in serum zinc levels between thalassemic children and healthy controls. There is  no significant correlation between serum ferritin and zinc in thalassemic children.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2671-2671 ◽  
Author(s):  
Emanuela Messa ◽  
Ilaria Defilippi ◽  
Antonella Roetto ◽  
Francesca Messa ◽  
Francesca Arruga ◽  
...  

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.


Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 340
Author(s):  
Fernando Salvador ◽  
Beatriz Lobo ◽  
Lidia Goterris ◽  
Carmen Alonso-Cotoner ◽  
Javier Santos ◽  
...  

Background: The aim of the present study is to describe the occurrence of Blastocystis sp. detection among asymptomatic subjects and patients with irritable bowel syndrome in order to evaluate the potential association between irritable bowel syndrome and the parasitic infection. Methods: Cross-sectional study where adult patients with irritable bowel syndrome diagnosed according to Rome IV criteria were included. A control group was formed by asymptomatic subjects older than 18 years. Exclusion criteria were: immunosuppressive condition or having received any drug with demonstrated activity against Blastocystis sp. within the last 6 months before study inclusion. Epidemiological and clinical information was collected from all included participants. Two stool samples were obtained from all participants: one sample for microscopic examination and one sample for Blastocystis sp. PCR detection. Blastocystis sp. infection was defined by the positivity of any of the diagnostic techniques. Results: Seventy-two participants were included (36 asymptomatic subjects and 36 patients with irritable bowel syndrome). Thirty-five (48.6%) were men, and median age of participants was 34 (IQR 29–49) years. The overall rate of Blastocystis sp. carriage was 27.8% (20/72). The prevalence assessed through microscopic examination was 22.2% (16/72), while the prevalence measured by PCR was 15.3% (11/72). When comparing the presence of Blastocystis sp. between asymptomatic subjects and IBS patients, we did not find any statistically significant difference (36.1% vs. 19.4% respectively, p = 0.114). Conclusions: regarding the occurrence of Blastocystis sp., no differences were found between asymptomatic participants and patients with irritable bowel disease irrespective of the diagnostic technique performed.


2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Sahar Mahmoud Shawky ◽  
Reeham Abdel Aziz Abdel Hamid ◽  
Lina Essam Khedr

Abstract Background Pruritus is a common and often distressing symptom in patients with chronic kidney disease. Though the pathogenesis of uremic pruritus remains poorly understood, systemic inflammation has presented itself as one of the possible explanations. High blood lead levels (BLLs) have been noted to be associated with inflammation and poor nutritional status in hemodialysis patients. Our aim is to study the relation between blood lead levels and uremic pruritus. This is a cross-sectional study that enrolled 50 patients; all were on regular hemodialysis 3 times per week for at least 6 months. Patients were divided into 2 groups, group 1 (n =10) with no pruritus and group 2 (n=40) with varying degrees of pruritus. Group 2 was further divided according to intensity of pruritus by visual analog score (VAS) into mild (n=10), moderate (n=20), and severe pruritus (n=10). Results There was a significant difference in serum lead levels and ferritin levels between groups 1 and 2 (p value < 0.01 and < 0.05, respectively). There was a statistically significant difference in serum lead levels in the groups with varying intensity of pruritus, having higher serum lead levels in patients who exhibited severe pruritus (p value < 0.005) Moreover, a statistically significant relation between elevated blood lead levels and the duration of dialysis was observed in this study. Conclusion Uremic pruritus is a multi-factorial phenomenon, and our study showed that blood lead levels in hemodialysis patients might be associated with increased intensity of pruritus.


2021 ◽  
pp. 1-7
Author(s):  
Emre Erdem ◽  
Ahmet Karatas ◽  
Tevfik Ecder

<b><i>Introduction:</i></b> The effect of high serum ferritin levels on long-term mortality in hemodialysis patients is unknown. The relationship between serum ferritin levels and 5-year all-cause mortality in hemodialysis patients was investigated in this study. <b><i>Methods:</i></b> A total of 173 prevalent hemodialysis patients were included in this study. The patients were followed for up to 5 years and divided into 3 groups according to time-averaged serum ferritin levels (group 1: serum ferritin &#x3c;800 ng/mL, group 2: serum ferritin 800–1,500 ng/mL, and group 3: serum ferritin &#x3e;1,500 ng/mL). Along with the serum ferritin levels, other clinical and laboratory variables that may affect mortality were also included in the Cox proportional-hazards regression analysis. <b><i>Results:</i></b> Eighty-one (47%) patients died during the 5-year follow-up period. The median follow-up time was 38 (17.5–60) months. The 5-year survival rates of groups 1, 2, and 3 were 44, 64, and 27%, respectively. In group 3, the survival was lower than in groups 1 and 2 (log-rank test, <i>p</i> = 0.002). In group 1, the mortality was significantly lower than in group 3 (HR [95% CI]: 0.16 [0.05–0.49]; <i>p</i> = 0.001). In group 2, the mortality was also lower than in group 3 (HR [95% CI]: 0.32 [0.12–0.88]; <i>p</i> = 0.026). No significant difference in mortality between groups 1 and 2 was found (HR [95% CI]: 0.49 [0.23–1.04]; <i>p</i> = 0.063). <b><i>Conclusion:</i></b> Time-averaged serum ferritin levels &#x3e;1,500 ng/mL in hemodialysis patients are associated with an increased 5-year all-cause mortality risk.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ádám László Nagy ◽  
Zsolt Tóth ◽  
Tamás Tarjányi ◽  
Nándor Tamás Práger ◽  
Zoltán Lajos Baráth

Abstract Background In this research the biomechanical properties of a bone model was examined. Porcine ribs are used as experimental model. The objective of this research was to investigate and compare the biomechanical properties of the bone model before and after implant placement. Methods The bone samples were divided in three groups, Group 1 where ALL-ON-FOUR protocol was used during pre-drilling and placing the implants, Group 2 where ALL-ON-FOUR protocol was used during pre-drilling, and implants were not placed, and Group 3 consisting of intact bones served as a control group. Static and dynamic loading was applied for examining the model samples. Kruskal–Wallis statistical test and as a post-hoc test Mann–Whitney U test was performed to analyze experimental results. Results According to the results of the static loading, there was no significant difference between the implanted and original ribs, however, the toughness values of the bones decreased largely on account of predrilling the bones. The analysis of dynamic fatigue measurements by Kruskal–Wallis test showed significant differences between the intact and predrilled bones. Conclusion The pre-drilled bone was much weaker in both static and dynamic tests than the natural or implanted specimens. According to the results of the dynamic tests and after a certain loading cycle the implanted samples behaved the same way as the control samples, which suggests that implantation have stabilized the skeletal bone structure.


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