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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective hematopoiesis that leads to peripheral cytopenias. Iron overload results from high transfusion requirements and retrospective studies have shown it to be associated with relatively poor survival in a subset of the low risk patients. Recent discoveries have led to the identification of hepcidin as a key regulator of iron metabolism and to the association of non-transferrin bound iron moieties, such as labile plasma iron, with the end organ damage in iron overload states. Currently, there is limited data in evaluating the role of iron chelators in MDS and data from studies in Thalassemia and hemachromostosis have been used to predict ferritin levels above 1000 - 2500 ng/mL and history of 20 blood transfusions as clinical end points for considering iron chelation in MDS. Deferoxamine and deferasirox, the two iron chelators approved for use in the US, have shown efficacy in reducing iron overload in MDS in retrospective studies are now being evaluated for effects on overall survival in prospective studies. On the basis of retrospective data, it is reasonable to offer iron chelation to the lower risk MDS patients requiring frequent transfusions, while monitoring for specific adverse affects in patients on treatment.
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PMID:Iron overload in myelodysplastic syndromes. 1829 18

Studies have shown that there is a relationship between zinc levels and depression. Thalassemic patients are at risk of zinc deficiency due to various causes including Desferal injection. The aim of this study, therefore, is to investigate hair zinc levels in thalassemic patients and their association with depression. For the purposes of this survey, 50 patients with major thalassemia between 10-20 years old were selected randomly. The patients' hair zinc concentration was compared with a control group of similarly aged healthy individuals. Simultaneously, their psychological status was evaluated with either the "Beck" or "Marya Kovacs" test (according to age) so that the relation between depression and zinc concentration could be assessed. The mean hair zinc concentration in patients was more than the controls (193.96 +/- 92.4 ppm vs 149.6 +/- 72.21 ppm). Zinc deficiency was present in 10% of the patients, and 52% had some degree of depression. There was a reverse correlation between zinc deficiency and blood transfusion rate (p < 0.05). Also, while there were more incidences of depression among the zinc deficient patients, the difference was not significant. Regarding the high prevalence of depression and insignificant relation to the zinc deficiency in these thalassemic patients, this research suggests the need for further consideration concerning patients' psychological status, the risk factors of zinc deficiency, as well as extended assessment into other causes of depression.
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PMID:Zinc in thalassemic patients and its relation with depression. 1833 12

A multicentre randomized open-label trial was designed to assess the effectiveness of long-term sequential deferiprone-deferoxamine (DFO-DFP) versus DFP alone to treat thalassaemia major (TM). DFP at 75 mg/kg, divided into three oral daily doses, for 4 d/week and DFO by subcutaneous infusion (8-12 h) at 50 mg/kg per day for the remaining 3 d/week was compared with DFP alone at 75 mg/kg, administered 7 d/week during a 5-year follow-up. The main outcome measures were differences between multiple observations of serum ferritin concentrations. Secondary outcomes were survival analysis, adverse events, and costs. Consecutive thalassaemia patients (275) were assessed for eligibility; 213 of these were randomized and underwent intention-to-treat analysis. The decrease of serum ferritin levels during the treatment period was statistically significant higher in sequential DFP-DFO patients compared with DFP-alone patients (P = 0.005). Kaplan-Meier survival analysis for the two chelation treatments did not show any statistically significant differences (long-rank test, P = 0.3145). Adverse events and costs were comparable between the groups. The trial results show that sequential DFP-DFO treatment compared with DFP alone significantly decreased serum ferritin concentration during treatment for 5 years without significant differences regarding survival, adverse events, or costs.
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PMID:Long-term sequential deferiprone-deferoxamine versus deferiprone alone for thalassaemia major patients: a randomized clinical trial. 1923 76

Non-transferrin bound iron (NTBI) is detectable in plasma of beta-thalassemia patients and participates in free-radical formation and oxidative tissue damage. Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are iron chelators used for treatment of iron overload; however they may cause adverse effects. Curcuminoids (CUR) exhibits many pharmacological activities and presents beta-diketone group to bind metal ions. Iron-chelating capacity of CUR was investigated in thalassemic mice. The mice (C57BL/6 stain); wild type ((mu)beta(+/+)) and heterozygous beta-knockout ((mu)beta(th-3/+)) were fed with ferrocene-supplemented diet for 2 months, and coincidently intervened with CUR (200 mg/kg/day) and DFP (50 mg/kg/day). Plasma NTBI was quantified using NTA chelation/HPLC method, and MDA concentration was analyzed by TBARS-based HPLC. Hepatic iron content (HIC) and total glutathione concentration were measured colorimetrically. Tissue iron accumulation was determined by Perl's staining. Ferrocene-supplemented diet induced occurrence of NTBI in plasma of thalassemic mice as well as markedly increased iron deposition in spleen and liver. Treatment with CUR and DFP decreased levels of the NTBI and MDA effectively. Hepatic MDA and nonheme iron content was also decreased in liver of the treated mice whilst total glutathione levels were increased. Importantly, the CUR and DFP reduced liver weight index and iron accumulation. Clearly, CUR is effective in chelation of plasma NTBI in iron-loaded thalassemic mice. Consequently, it can alleviate iron toxicity and harmfulness of free radicals. In prospective, efficacy of curcumin in removal of labile iron pool (LIP) in hepatocytes and cardiomyocytes are essential for investigation.
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PMID:Efficacy of curcuminoids in alleviation of iron overload and lipid peroxidation in thalassemic mice. 1953 81

Patients receiving recurring blood transfusions as supportive therapy to treat chronic anemias, such as myelodysplastic syndromes, thalassemia, and sickle-cell disease, are at risk of iron accumulation. The clinical consequences of iron overload are progressive liver damage, cardiac disease, and endocrine disorders, which can be fatal. Nurses have a vital role in the initial assessment and monitoring of patients undergoing transfusion therapy and their ongoing care. Iron levels may be managed effectively with iron chelation therapy, and treatment guidelines recommend initiation when serum ferritin levels reach more than 1,000 mcg/L. Deferoxamine has been used effectively in clinical practice for more than 40 years. Newer agents, such as deferasirox, have introduced the option of oral therapy to manage iron overload. Those agents and practical management of patients receiving multiple blood transfusions are discussed.
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PMID:Understanding iron overload: screening, monitoring, and caring for patients with transfusion-dependent anemias. 1979 8

Deferoxamine (DFO) is an iron chelator used to treat iron overload in patients receiving chronic blood transfusions, and is usually administered as overnight subcutaneous infusions. ISOSFER was a prospective, observational, cross-sectional study conducted in metropolitan France that evaluated patient characteristics, quality of life (QoL), compliance and patient satisfaction with DFO monotherapy. Of 70 patients with either thalassemia, sickle cell disease or myelodysplastic syndromes, 30% were 'satisfied' or 'very satisfied' with DFO. Patients' SF-36 scores were lower than those of the general French population, and lower among patients with comorbidities and those dissatisfied with treatment. Although 72% of patients had good compliance to DFO, 57% reported missing at least one infusion in the previous month, and 82% of patients expressed a preference for oral therapy. These results suggest that QoL is severely compromised in patients receiving DFO, and that compliance is not optimal.
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PMID:Socio-psychological impact of infused iron chelation therapy with deferoxamine in metropolitan France: ISOSFER study results. 1994 37

Desferrioxamine B (DFOB) conjugates with adamantane-1-carboxylic acid, 3-hydroxyadamantane-1-carboxylic acid, 3,5-dimethyladamantane-1-carboxylic acid, adamantane-1-acetic acid, 4-methylphenoxyacetic acid, 3-hydroxy-2-methyl-4-oxo-1-pyridineacetic acid (N-acetic acid derivative of deferiprone), or 4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic acid (deferasirox) were prepared and the integrity of Fe(III) binding of the compounds was established from electrospray ionization mass spectrometry and RP-HPLC measurements. The extent of intracellular (59)Fe mobilized by the DFOB-3,5-dimethyladamantane-1-carboxylic acid adduct was 3-fold greater than DFOB alone, and the IC(50) value of this adduct was 6- or 15-fold greater than DFOB in two different cell types. The relationship between logP and (59)Fe mobilization for the DFOB conjugates showed that maximal mobilization of intracellular (59)Fe occurred at a logP value approximately 2.3. This parameter, rather than the affinity for Fe(III), appears to influence the extent of intracellular (59)Fe mobilization. The low toxicity-high Fe mobilization efficacy of selected adamantane-based DFOB conjugates underscores the potential of these compounds to treat iron overload disease in patients with transfusional-dependent disorders such as beta-thalassemia.
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PMID:Conjugates of desferrioxamine B (DFOB) with derivatives of adamantane or with orally available chelators as potential agents for treating iron overload. 2004 72

beta-thalassaemia has served as a paradigm for chelation management for over three decades, both in terms of defining the complications of transfusional iron overload, and demonstrating the benefits of chelation therapy. Iron chelation therapy can be used to reduce unacceptably high tissue iron levels, or to maintain current levels if these are deemed safe, by matching the rate of transfused iron. Chelation therapy should be tailored to the individual patient, based on the transfusional iron loading rate and the current level of iron load both intra- and extra-hepatically, for example in the myocardium. In general, it is preferable to prevent extra-hepatic complications by controlling the body iron load rather than attempting to rescue patients once extra-hepatic complications have developed. Deferoxamine, which has been available since the late 1970s and is given parenterally, has been shown to prolong life and decrease morbidity from iron overload in patients who comply with therapy. Deferiprone may control body iron as oral monotherapy in a variable proportion of patients but is now more frequently used in combinations with deferoxamine, either to control total levels of body iron or to reduce increased levels of myocardial iron. In this article, recent advances in the use of deferasirox, a once-daily oral iron chelator, are reviewed. Large-scale prospective trials show efficacy with an acceptable safety profile in adults and children with up to 5 years follow-up. Recent evidence suggests that deferasirox up to 30 mg/kg/day can be safely administered to patients with serum ferritin levels between 500 and 1000 mg/L, while doses above 30 mg/kg/day can be given to patients with substantial iron overload or with high transfusion rates. Further, prospective data show that myocardial iron can be effectively decreased with this chelation treatment.
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PMID:Optimizing iron chelation strategies in beta-thalassaemia major. 2011 37

Iron overload is a serious and potentially fatal condition that results from multiple blood transfusions required over a long period of time to treat certain types of anemias such as, that caused by beta-thalassemia, sickle cell disease and myelodysplastic syndrome. Deferoxamine, which has been used since four decades as an iron chelator has limited efficacy due to its demanding therapeutic regimen, leading to poor compliance. Deferasirox, once daily oral iron chelator provides an effective alternative to Deferoxamine in the treatment of transfusional hemosiderosis. In this review, the role of Deferasirox as an ideal iron chelator has been discussed. Pubmed searches on Deferasirox were carried out for the same. Several studies demonstrated the safety and efficacy of Deferasirox in reducing iron burden in iron-overloaded patients with beta-thalassemia, sickle cell anemia and myelodysplastic anemia. Thus, convenient, effective and tolerable chelation therapy with oral Deferasirox is likely to be a significant development in the treatment of transfusional iron overload, due to its ability to provide constant chelation coverage and the potential to improve compliance.
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PMID:Deferasirox: oral, once daily iron chelator--an expert opinion. 2017 10

Millions of people are affected by hereditary hemochromatosis (HH) and thalassemia intermedia (TI), the iron overloading disorders caused by chronic increases in iron absorption. Genetic factors, regulatory pathways involving proteins of iron metabolism, non regulatory molecules, dietary constituents and iron binding drugs could affect iron absorption and could lead to iron overload or iron deficiency. Chelators and chelating drugs can affect both iron absorption and excretion. Deferoxamine (DFO), deferiprone (L1) and the DFO/L1 combination therapies have been used effectively for reversing the toxic side effects of iron overload including cardiac and liver damage in TI and HH patients where venesection is contraindicated. Selected protocols using DFO, L1 and their combination could be designed for optimizing chelation therapy in TI and HH. The use of deferasirox (DFRA) in HH and TI could cause an increase in iron and other toxic metal absorption. Future treatments of HH and TI could involve the use of iron chelating and other drugs not only for increasing iron excretion but also for preventing iron absorption.
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PMID:Iron chelation therapy in hereditary hemochromatosis and thalassemia intermedia: regulatory and non regulatory mechanisms of increased iron absorption. 2159 42


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