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Medicine Mar 2024Compound heterozygotes for deletional β-thalassemia can be difficult to diagnose due to its diverse clinical presentations and no routine screenings. This can lead to...
Compound heterozygosity for Southeast Asian hereditary persistence of fetal hemoglobin and β0-thalassemia results in thalassemia intermedia: Pedigree analysis and genetic research in a family from South China. A case report.
RATIONALE
Compound heterozygotes for deletional β-thalassemia can be difficult to diagnose due to its diverse clinical presentations and no routine screenings. This can lead to disease progression and delay in treatment.
PATIENT CONCERNS
We reported pedigree analysis and genetic research in a family with rare β-thalassemia.
DIAGNOSIS
Pedigree analysis and genetic research demonstrated that the patient was a compound heterozygote for β-thalassemia CD17/Southeast Asian hereditary persistence of fetal hemoglobin deletion, inherited from the parents. Magnetic resonance imaging T2* examination revealed severe iron deposition in the liver. Echocardiography revealed endocardial cushion defect.
INTERVENTIONS
The patient was treated with Deferasirox after receiving the final molecular genetic diagnosis. The initial once-daily dose of Deferasirox was 20 mg/kg/d.
OUTCOMES
The patient discontinued the medication three months after the first visit. Two years later, the patient visited the Department of Hepatobiliary and Pancreatic Diseases. He was recommended to undergo splenectomy after surgical repair of the congenital heart disease. However, the patient refused surgical treatment because of the economic burden.
LESSONS
We report that fetal hemoglobin is a sensitive indicator for screening large deletions of the β-globin gene, which can be effectively confirmed by the multiplex ligation-dependent probe amplification assay. In non-transfusion-dependent thalassemia patients, iron status assessment should be regularly performed, and iron chelation treatment should be initiated early. This case will provide insights for the diagnosis of rare genotypes of β-thalassemia and has important implications for genetic counseling.
Topics: Male; Humans; beta-Thalassemia; Fetal Hemoglobin; Pedigree; Deferasirox; Southeast Asian People; Genetic Research; China; Iron; Heterozygote
PubMed: 38457547
DOI: 10.1097/MD.0000000000037446 -
Cureus Feb 2024This network meta-analysis was conducted with the aim of comparing the efficacy and safety of deferiprone (DFP), deferasirox (DFX), and deferoxamine (DFO) in individuals... (Review)
Review
Compare the Efficacy and Safety of Deferoxamine, Deferasirox, and Deferiprone in Patients With Sickle Cell Disease or Transfusion-Dependent Anemia: A Network Meta-Analysis of Randomized Control Trials.
This network meta-analysis was conducted with the aim of comparing the efficacy and safety of deferiprone (DFP), deferasirox (DFX), and deferoxamine (DFO) in individuals with sickle cell disease (SCD) or transfusion-dependent anemia. This systematic review and meta-analysis adhered to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines. The search was conducted on electronic databases, including PubMed, CINAHIL, and EMBASE, from the inception of databases to January 10, 2024. Outcomes assessed in this study included a change in liver iron concentration (LIC) and a change in ferritin from baseline. For safety analysis, adverse events were compared among three treatment groups. A total of five studies were included in this meta-analysis. The pooled analysis showed that the change in LIC and serum ferritin from baseline was not significantly different in patients with SCD or other anemias. In terms of adverse events, deferiprone was the safest among all. In conclusion, deferiprone demonstrated noninferiority to deferoxamine and deferasirox in measures of iron load, presenting a viable treatment option. Safety outcomes revealed deferasirox carried a higher risk of adverse events compared to deferiprone, supporting its favorable safety profile.
PubMed: 38455804
DOI: 10.7759/cureus.53644 -
Turkish Archives of Pediatrics Mar 2024To investigate the effect of switching from deferasirox dispersible tablet (DT) to deferasirox film-coated tablet (FCT) on serum ferritin (SF) levels in...
Switching from Deferasirox Dispersible Tablets to Deferasirox Film-Coated Tablets: Is There an Effect on Ferritin Levels in Children and Adolescents with Transfusion-Dependent Anemia?
OBJECTIVE
To investigate the effect of switching from deferasirox dispersible tablet (DT) to deferasirox film-coated tablet (FCT) on serum ferritin (SF) levels in transfusion-dependent patients.
MATERIALS AND METHODS
Patients who received regular erythrocyte transfusion and whose treatment was switched from DT to FCT were included in the study. FCT start date was taken as the index date. Patients were followed over 2 equal and long periods, both before and after index date.
RESULTS
Thirty-two patients were included, and the comparison periods ranged from 4 to 12 months. The SF values increased from a median of 1723 ng/mL (range 717-5369 ng/mL) to 1.853 ng/mL (range 924-5478 ng/mL) after switching from DT to FCT (P = .036). While there was a significant increase in median SF after switching in Turkish patients (1467 ng/mL to 1778 ng/ mL, P = .010) and patients ≥12 years (1598-1848 ng/mL, P = .009), there was an insignificant (P = .859) decrease in SF in immigrant children. Considering only the post-switch period, there was a non-significant increase in median SF in the entire cohort, while SF decreased significantly in immigrant children (P = .026). No serious side effects were observed in any patient that would cause discontinuation of treatment.
CONCLUSION
Overall, higher SF value was observed with FCT compared to DT in short term. There were different results between patient groups. Our results suggest that FCT is more effective than DT in patients with high basal ferritin and who are actually incompatible with treatment and should be preferred first in these patients.
PubMed: 38454229
DOI: 10.5152/TurkArchPediatr.2024.23262 -
Profiles of Drug Substances,... 2024Deferasirox is an iron-chelating drug developed by Novartis company for treatment of diseases accompanied by chronic iron overload; such as β-thalassemia or sickle cell...
Deferasirox is an iron-chelating drug developed by Novartis company for treatment of diseases accompanied by chronic iron overload; such as β-thalassemia or sickle cell diseases. Owing to its advantages such as high affinity, specificity and wide therapeutic window, it is considered as first line treatment. The current chapter describes the physicochemical characteristics, mode of action, pharmacokinetics, therapeutic applications and synthetic methods for deferasirox. Moreover, it includes Fourier transform infrared spectrometry (FTIR) and nuclear magnetic resonance spectroscopy (NMR) analysis for its functional groups. In addition, the selected analytical methods are summarized to aid the analysts in their routine analysis of deferasirox.
Topics: Humans; Deferasirox; Benzoates; Triazoles; Iron Chelating Agents; Iron Overload; Iron
PubMed: 38423705
DOI: 10.1016/bs.podrm.2023.11.001 -
Haematologica Feb 2024Not available.
Not available.
PubMed: 38385265
DOI: 10.3324/haematol.2023.283610 -
Hemoglobin Jan 2024The study aimed to determine efficacy and safety of generic deferasirox monotherapy. Deferasirox was administered in transfusion-induced iron overloaded thalassemia....
The study aimed to determine efficacy and safety of generic deferasirox monotherapy. Deferasirox was administered in transfusion-induced iron overloaded thalassemia. Efficacy was defined as responders and nonresponders by ≤ 15 reduced serum ferritin from baseline. Adverse events were also monitored. Fifty-two patients with mainly Hb E/β-thalassemia at the mean (SD) age of 8.7 (4.1) years, were enrolled. The mean (SD) daily transfusion iron load was 0.47 (0.1) mg/kg and maximum daily deferasirox was 35.0 (6.2) mg/kg. Altogether, 52, 40 and 18 patients completed the first, second and third years of study, respectively. The median baseline serum ferritin 2,383 ng/mL decreased to 1,478, 1,038 and 1,268 ng/mL at the end of first, second and third years, respectively, with overall response rate at 73.1% (38/52). Patients with baseline serum ferritin >2,500 ng/mL showed a change in serum ferritin higher than those ≤2,500 ng/mL starting from the 9th month of chelation. Adverse events were found in 5 of 52 patients (9.6%) including transaminitis (n = 2), one each of proteinuria, rash and proximal tubular dysfunction which resolved after transient stopping or decreasing the chelation dose. Generic deferasirox was effective and safe among pediatric patients with transfusion-induced iron overloaded thalassemia.
Topics: Humans; Child; Deferasirox; Iron Chelating Agents; Benzoates; Triazoles; Iron Overload; Thalassemia; Iron; Ferritins
PubMed: 38369714
DOI: 10.1080/03630269.2024.2311360 -
British Journal of Haematology May 2024Iron overload from repeated transfusions has a negative impact on cardiac function, and iron chelation therapy may help prevent cardiac dysfunction in... (Randomized Controlled Trial)
Randomized Controlled Trial
Iron overload from repeated transfusions has a negative impact on cardiac function, and iron chelation therapy may help prevent cardiac dysfunction in transfusion-dependent patients with myelodysplastic syndromes (MDS). TELESTO (NCT00940602) was a prospective, placebo-controlled, randomised study to evaluate the iron chelator deferasirox in patients with low- or intermediate-1-risk MDS and iron overload. Echocardiographic parameters were collected at screening and during treatment. Patients receiving deferasirox experienced a significant decrease in the composite risk of hospitalisation for congestive heart failure (CHF) or worsening of cardiac function (HR = 0.23; 95% CI: 0.05, 0.99; nominal p = 0.0322) versus placebo. No significant differences between the arms were found in left ventricular ejection fraction, ventricular diameter and mass or pulmonary artery pressure. The absolute number of events was low, but the enrolled patients were younger than average for patients with MDS, with no serious cardiac comorbidities and a modest cardiovascular risk profile. These results support the effectiveness of deferasirox in preventing cardiac damage caused by iron overload in this patient population. Identification of patients developing CHF is challenging due to the lack of distinctive echocardiographic features. The treatment of iron overload may be important to prevent cardiac dysfunction in these patients, even those with moderate CHF risk.
Topics: Humans; Deferasirox; Myelodysplastic Syndromes; Male; Female; Iron Chelating Agents; Middle Aged; Aged; Iron Overload; Prospective Studies; Benzoates; Heart Failure; Transfusion Reaction; Echocardiography; Adult; Aged, 80 and over; Triazoles; Blood Transfusion
PubMed: 38343073
DOI: 10.1111/bjh.19316 -
PloS One 2024Agomelatine (AGO) is an antidepressant with unique pharmacological effects; however, its underlying mechanisms remain unknown. In this study, we examined agomelatine's...
BACKGROUND
Agomelatine (AGO) is an antidepressant with unique pharmacological effects; however, its underlying mechanisms remain unknown. In this study, we examined agomelatine's effects on catalase activity, oxidative stress, and inflammation.
METHODS
Chronic restraint stress (CRS) model mice were established over 4 weeks, and AGO 50 mg/kg was administered to different groups alongside a deferasirox (DFX) 10 mg/kg gavage treatment. Behavioral tests were performed to assess the effect of AGO on the remission of depression-like behaviors. Meanwhile, the expression of CAT, the oxidative stress signaling pathway and inflammatory protein markers were assessed using ELISA, qRT-PCR, Western blot, and immunohistochemistry.
RESULTS
Four weeks of AGO treatment significantly improved depression-like behavior in mice through the activation of catalase in the hippocampus and serum of the model mice, increased superoxide dismutase expression, reduced malondialdehyde expression, and reduced oxidative stress damage. Deferasirox was found to offset this therapeutic effect partially. In addition, the inflammatory pathway (including nuclear factor-κB and nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) was not significantly altered.
CONCLUSIONS
AGO can exert antidepressant effects by altering oxidative stress by modulating catalase activity.
Topics: Mice; Animals; Depression; Catalase; Deferasirox; Antioxidants; Oxidative Stress; Antidepressive Agents
PubMed: 38335199
DOI: 10.1371/journal.pone.0289248 -
BMJ Open Feb 2024Despite the improvement in medical management, many patients with transfusion-dependent β-thalassaemia die prematurely due to transfusion-related iron overload. As per...
Efficacy and safety of deferoxamine, deferasirox and deferiprone triple iron chelator combination therapy for transfusion-dependent β-thalassaemia with very high iron overload: a protocol for randomised controlled clinical trial.
INTRODUCTION
Despite the improvement in medical management, many patients with transfusion-dependent β-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent β-thalassaemia with very high iron overload.
METHODS AND ANALYSIS
This is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent β-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6 months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6 months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures.
ETHICS AND DISSEMINATION
Ethical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P/06/02/2023). The trial results will be disseminated in scientific publications in reputed journals.
TRIAL REGISTRATION NUMBER
The trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR/2023/010).
Topics: Adult; Adolescent; Humans; Deferasirox; Deferiprone; Deferoxamine; beta-Thalassemia; Benzoates; Triazoles; Pyridones; Iron Overload; Iron Chelating Agents; Iron; Randomized Controlled Trials as Topic
PubMed: 38331857
DOI: 10.1136/bmjopen-2023-077342