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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Few areas concerning the care of patients with myelodysplastic syndromes (MDS) have prompted as much disagreement among clinicians as the appropriate role of iron chelation therapy. At least eight conflicting guidelines or consensus statements on iron management in MDS have been published by medical organizations during the past 6 years. Uncertainties about the clinical importance of iron overload and the necessity for iron chelation in transfusion-requiring patients with MDS have caused confusion for patients. Here, I summarize what we have learned and what we still do not know about the diagnosis, prognosis, monitoring and treatment of iron overload in patients with MDS, including the merits and drawbacks of the oral iron chelator, deferasirox. I also draw parallels between iron and radon with respect to the possibility of biological harm, lack of definitive study results, existence of groups at special risk, and fear that the ongoing uncertainties about these elements incite in patients.
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PMID:Myelodysplasia paranoia: iron as the new radon. 1903 43

Iron overload occurs in patients who require regular blood transfusions to correct genetic and acquired anaemias, such as beta-thalassaemia major, sickle cell disease, and myelodysplastic syndromes. Although iron overload causes damage in many organs, accumulation of cardiac iron is a leading cause of death in transfused patients with beta-thalassaemia major. The symptoms of cardiac iron overload will occur long after the first cardiac iron accumulation, at a point when treatment is more complex than primary prevention would have been. Direct measurement of cardiac iron using T2* magnetic resonance imaging, rather than indirect methods such as measuring serum ferritin levels or liver iron concentration have contributed to earlier recognition of myocardial iron loading and prevention of cardiac toxicity. Cardiac siderosis occurs in all transfusional anaemias, but the relative risk depends upon the underlying disease state, transfusional load, and chelation history. All three available iron chelators can be used to remove cardiac iron, but each has unique physical properties that influence their cardiac efficacy. More prospective trials are needed to assess the effects of single-agent or combination iron chelation therapy on the levels of cardiac iron and cardiac function. Ultimately, iron chelation therapies should be tailored to meet individual patient needs and lifestyle demands.
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PMID:Cardiac iron across different transfusion-dependent diseases. 1905 52

Haemopoietic stem cell transplantation (HSCT) is an important intervention for malignant and non-malignant blood diseases. However, HSCT is also associated with considerable morbidity and mortality, some of which may be related to iron overload. Levels of serum iron are elevated in patients undergoing HSCT as a result of disturbed iron metabolism, pre-transplantation blood transfusions, or cytotoxic therapy for conditioning before HSCT. The complications of iron overload in HSCT patients include infections, mucositis, chronic liver disease (fibrosis progression), sinusoidal obstruction syndrome, and idiopathic pneumonia syndrome. Iron overload has an adverse impact on survival in patients undergoing HSCT for beta-thalassaemia major or haematological malignancies including myelodysplastic syndromes. It has been suggested that all candidates for and all survivors of HSCT should be screened for iron overload at various time points before and after transplantation. Few studies of iron chelation therapy after HSCT have been reported, but one small study has indicated that deferoxamine is at least as effective as phlebotomy in reducing post-transplantation iron overload in patients with beta-thalassaemia major. The new oral chelator deferasirox may be better tolerated than phlebotomy or deferoxamine infusion, and two prospective phase II studies in patients with iron overload after HSCT are now recruiting candidates.
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PMID:The role of iron in patients after bone marrow transplantation. 1905 53

Many patients with myelodysplastic syndromes (MDS) have severe anaemia. However, regular blood transfusions, which are widely used to maintain quality of life and prevent anaemia-related morbidity and mortality, have a negative impact on survival as a result of iron overload. Retrospective surveys have shown an association of transfusion dependence with hepatic, pituitary, and pancreatic dysfunction, cardiac failure, and cardiac death. Survival is significantly decreased in transfusion-dependent patients, and the main cause of non-leukaemic death is cardiac failure. However, iron chelation therapy reduces serum ferritin levels and is associated with significantly improved survival in patients with MDS. Current guidelines recommend starting iron chelation therapy after 25-50 units of blood have been transfused, or when serum ferritin levels rise above 1,000-2,000 microg/L. The patients who are most likely to benefit from iron chelation therapy are those who have low-risk disease (International Prognostic Scoring System low or intermediate-1 risk) with a life expectancy of more than 1 year. More specific studies in patients with MDS are needed to evaluate the impact of iron chelation therapy on morbidity and mortality, and provide a stronger evidence base for treatment guidelines.
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PMID:The deleterious effects of iron overload in patients with myelodysplastic syndromes. 1905 54

Most patients with myelodysplastic syndrome eventually become dependent on regular red cell transfusions. This dependency has a negative impact on clinical outcome, primarily because it may be associated with more severe marrow failure. In addition, however, transfusion dependency may involve clinical consequences of chronic anemia and iron overload. Although transfusion iron is primarily taken up by the reticuloendothelial cells, the metal is later redistributed to parenchymal cells. This redistribution is modulated by several factors, including the degree of ineffective erythropoiesis through its suppressive effect on hepcidin production. Body iron status is routinely assessed by serum ferritin and transferrin saturation, but there is a need of reliable tools for locating iron accumulation in patients. Magnetic resonance imaging T2* provides a non-invasive method for detecting and quantifying both liver and myocardial iron overload. Clinical consequences of parenchymal iron overload have been reported not only in thalassemia major, but also in patients with myelodysplastic syndrome. Transfusion-dependent patients with isolated erythroid dysplasia and low risk of leukemic evolution are more likely to develop parenchymal iron overload and its toxicity, and therefore may benefit from chelation therapy. There may also be a benefit of chelation therapy in patients with transfusion iron overload undergoing allogeneic stem cell transplantation. Deferoxamine and deferasirox are currently available for treatment of transfusion iron overload in patients with myelodysplastic syndrome.
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PMID:Clinical relevance of anemia and transfusion iron overload in myelodysplastic syndromes. 1907 76

Imbalances of iron homeostasis cause frequent clinical syndromes. Iron deficiency affects almost 25% of the global population and approximately one billion people suffer from iron deficiency anaemia. Moreover, the anaemia of chronic disease, which develops primarily in subjects suffering from malignancies, infections and autoimmune disorders is pivotally caused by an iron-limited erythropoiesis, which arises from iron retention within cells of the reticulo endothelial system. In contrast, one of the most frequent inherited disorders in people of Northern-Western European origin is hereditary hemochromatosis (HH). HH leads to progressive iron overload in parenchymal organs with subsequent organ failure. In addition, secondary iron overload develops in patients receiving repetitive blood transfusion for the treatment of genetic hemoglobinopathies or for the correction of anaemia in cancer or myelodysplastic syndromes. Due to the discovery of new genes, our knowledge on the regulation of iron homeostasis has dramatically expanded which offers avenues for new treatment options. This is of importance, since some of these clinical syndromes (e.g. anaemia of chronic disease or secondary iron overload) are not sufficiently treatable with current medications (e.g. iron chelators, iron, erythropoietin) in many patients. In addition, some patients with iron deficiency face side effects from iron therapy or refuse phlebotomy for treatment of HH. Thus, new treatment strategies for iron metabolism disorders or improvement of existing concepts are necessary. This review discusses established, approaching and future putative treatment strategies and concepts for combating iron metabolism disorders.
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PMID:New pharmacological concepts for the treatment of iron overload disorders. 1919 23

Iron overload, characterized by excessive iron deposition, occurs commonly in patients with hereditary or refractory anemias such as beta-thalassemia major, sickle cell anemia, and myelodysplastic syndromes, whose anemia is managed with frequent blood transfusions. Without adequate iron chelation therapy, almost all patients with beta-thalassemia will accumulate potentially fatal iron levels. Myocardial siderosis and resulting cardiac complications are among the leading causes of death in such patients. Unfortunately, even with the administration of effective subcutaneous iron chelation therapy with desferrioxamine (DFO), over 50% of patients die before the age of 35 years, largely because of poor compliance with subcutaneous chelation regimens. Recently introduced oral chelation agents, deferiprone and deferasirox, are associated with higher compliance rates, and greater reductions in cardiac iron levels, than those achieved with DFO. This article reviews the pharmacologic properties and clinical efficacy of currently available iron chelation therapies in the management of transfusional chronic iron overload.
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PMID:Treatment of iron overload in thalassemia. 1933 80

Patients with myelodysplastic syndromes (MDS) often require chronic RBC transfusions, which can lead to iron overload. Without adequate management, this may cause progressive damage to hepatic, endocrine, and cardiac organs, significantly affecting overall survival. Recent retrospective analyses have suggested that iron chelation provides a survival advantage in iron-overloaded patients with MDS who are given chelation therapy compared with those who are not. Nonetheless, it is evident that iron overload in many patients with MDS is not adequately managed. Clinical evaluation of the once-daily, oral iron chelator deferasirox in MDS populations has indicated that it provides dose-dependent reductions in body iron burden and is generally well tolerated, with a manageable safety profile in adult and pediatric patients. The most common treatment-related adverse events (AEs) included transient, mild-to-moderate gastrointestinal disturbances and skin rash, which rarely required drug discontinuation and resolved spontaneously in most cases. Adequate management of AEs and practical approaches such as patient education and counseling are necessary to ensure that patients remain compliant with therapy. Regular monitoring of serum ferritin levels is key to identifying patients who require iron chelation therapy, and to ensure maintenance of iron levels below the critical level of 1,000 microg/l. The flexible dosing regimen of deferasirox allows dose adjustments to be made in response to trends in serum ferritin, to changes in a patient's transfusional iron intake, and to the objectives of treatment, allowing the full benefit of transfusion therapy without the risks associated with iron overload.
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PMID:Managing iron overload in patients with myelodysplastic syndromes with oral deferasirox therapy. 1936 94

Myelodysplastic syndrome (MDS) is relatively common, with an incidence estimated as high as 50 cases per 100,000 people per year. This cancer mainly affects older (>or=60 years) patients. MDS refers to a collection of hematologic malignancies that share an ineffective production, or hematopoiesis, of normal bone marrow or myeloid cells. As progressive bone marrow failure occurs, patients generally display gradually worsening cytopenias specific to the type of bone marrow cell affected, such as thrombocytopenia or neutropenia. MDS patients often develop disease-related anemia requiring chronic blood transfusion; this can lead to complications including iron overload. As MDS progresses and the number of bone marrow blasts increases, the disease transforms into acute myelogenous leukemia (AML). Several classification systems have been developed to identify and differentiate particular types of MDS. Proper identification is essential, allowing the oncologist to determine prognosis, as well as the optimal therapeutic strategy. Several agents have been developed or are under investigation for the treatment of MDS, with the therapeutic goal of increasing survival and decreasing the rate of AML transformation. Currently, 3 agents are FDA-approved: azacitidine, decitabine, and lenalidomide. This clinical roundtable will discuss the optimal management of patients with each of these approved therapies, as well as the various classification systems used to differentiate MDS subtypes for treatment.
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PMID:Recent advances in low- and intermediate-1-risk myelodysplastic syndrome: developing a consensus for optimal therapy. 1938 3

We present a retrospective analysis of 137 patients with early MDS without excess of blasts that revealed transfusion dependency in 87% of the cases. A significant difference in overall survival was noted between patients receiving <or=2 units and those receiving >2 units of RBC transfusions/month (65.0 vs. 35.3 months, respectively, P=0.02). Univariate statistical analysis identified the presence of disease progression to advanced MDS (chi(2)=26.4, P=0.001) and the administration of >1 or >2 units of RBC per month (chi(2)=15.9 and 14.6, respectively, P=0.001) as the most important parameters affecting survival. Nevertheless, even the administration of 1 RBC unit every 4-8 weeks had a significantly adverse impact on survival compared to non-transfused patients. Transfusion dependency itself did not affect disease progression as determined by the presence of multilineage dysplasia and adverse karyotype (expressed by the IM-1 or IM-2 score). Multivariate analysis confirmed disease progression towards leukemia as a highly significant independent variable affecting survival (P=0.0001). None of the other evaluated parameters had a significant impact on survival in patients with progressive disease. In non-transplanted patients without MDS progression, administration of >2 units of RBC transfusions/month was the only independent variable with adverse impact on survival in patients with unilineage erythroid dysplasia (P=0.02). In patients with multilineage dysplasia, only heavy transfusion dependency (>3TURBC/month) and serum ferritin >2000 microg/l adversely affected survival (P=0.03). Modification of the WPSS by replacing transfusion dependency with initial Hb level <80 g/l retained its prognostic relevance and allowed the identification of a potential risk subset of early MDS patients with intermediate and high scores and limited survival (<40% at 5 years) as early as at the time of diagnosis. Our results confirm a significant negative impact of transfusion dependency on survival in patients with early MDS without excess of blasts. The main risk subgroup is characterized by unilineage dysplasia limited to erythropoiesis in combination with dependency on >2TU of RBC per month. These patients usually have prolonged survival that leads to the development of heavy transfusion iron overload and they thus represent the most important target group for intensive chelation therapy.
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PMID:Impact of transfusion dependency on survival in patients with early myelodysplastic syndrome without excess of blasts. 1964 56


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