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Aims: To compare insulin sensitivity, β-cell function and iron status biomarkers in non-transfusion-dependent thalassaemia (NTDT) with iron excess during pre- and post-iron chelation. Methods: Subjects with NTDT, aged older than 10 years, with serum ferritin >300 ng/ml, were included. Iron chelation with deferasirox (10 mg/kg/day) was prescribed daily for 6 months. Results: Ten patients with a median age of 17.4 years were enrolled. The comparison between pre- and post-chelation demonstrated significantly lower iron load: median serum ferritin (551.4 vs. 486.2 ng/ml, p = 0.047), median TIBC (211.5 vs. 233.5 µg/dl, p = 0.009) and median non-transferrin binding iron (5.5 vs. 1.4 µM, p = 0.005). All patients had a normal oral glucose tolerance test (OGTT) both pre- and post-chelation. However, fasting plasma glucose was significantly reduced after iron chelation (85.0 vs.79.5 mg/dl, p = 0.047). MRI revealed no significant changes of iron accumulation in the heart and liver after chelation, but there was a significantly lower iron load in the pancreas, assessed by higher T2* at post-chelation compared with pre-chelation (41.9 vs. 36.7 ms, p = 0.047). No adverse events were detected. Conclusions: A trend towards improving insulin sensitivity and β-cell function as well as a reduced pancreatic iron load was observed following 6 months of iron chelation (TCTR20160523003). [ABSTRACT FROM AUTHOR]

Iron overload in transfusion-dependent patients with rare anemias can be managed with chelation therapy. This study evaluated deferasirox efficacy and safety in patients with myelodysplastic syndromes (MDS), aplastic anemia (AA) or other rare anemias. A 1-year, open-label, multicenter, single-arm, phase II trial was performed with deferasirox (10-40 mg/kg/day, based on transfusion frequency and therapeutic goals), including an optional 1-year extension. The primary end point was a change in liver iron concentration (LIC) after 1 year. Secondary end points included changes in efficacy and safety parameters (including ophthalmologic assessments) overall as well as in a Japanese subpopulation. Overall, 102 patients (42 with MDS, 29 with AA and 31 with other rare anemias) were enrolled; 57 continued into the extension. Mean absolute change in LIC was -10.9 mg Fe/g dry weight (d.w.) after 1 year (baseline: 24.5 mg Fe/g d.w.) and -13.5 mg Fe/g d.w. after 2 years. The most common drug-related adverse event was increased serum creatinine (23.5%), predominantly in MDS patients. Four patients had suspected drug-related ophthalmologic abnormalities. Outcomes in Japanese patients were generally consistent with the overall population. Results confirm deferasirox efficacy in patients with rare anemias, including a Japanese subpopulation. The safety profile was consistent with previous studies and ophthalmologic parameters generally agreed with baseline values (EUDRACT 2006-003337-32). © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy of combined treatment with oral and subcutaneous iron chelators. Material and Methods: 50-100 mg/kg/day of oral deferiprone (DFP) combined with 40 mg/kg/dose s.c. desferrioxamine (DFO) twice weekly were given to transfusion-dependent β-thalassemia children. Results: Enrolled patients (9 with β-thalassemia major and 33 with β-thalassemia hemoglobin E), ranging from 3 to 18 years in age, were divided into 3 groups; group 1 ferritin ≥1,000-2,500 ng/ml (n = 10), group 2 ferritin >2,500-4,000 ng/ml (n = 23) and group 3 ferritin >4,000 ng/ml (n = 9). Of the 42 patients, 28 reached the 36-month follow-up. Ten patients whose ferritin declined <15% while receiving 100 mg/kg/day of DFP were considered nonresponders. The median age and previous transfusion duration before enrollment were significantly higher in nonresponders than responders (p = 0.04 and 0.003, respectively). The responders exhibited a significant fall in median ferritin levels from 2,954.6 to 936.6 ng/ml (p < 0.001). Time to a significant decrease in serum ferritin among responders was 6 months. In 13 patients, 16 episodes of adverse events occurred: hemophagocytosis with cytopenia (n = 1), neutropenia (n = 2), thrombocytopenia (n = 2), elevated alanine aminotransferase (n = 5), elevated serum creatinine (n = 1), proteinuria (n = 1) and gastrointestinal discomfort (n = 4). Conclusion: Combination therapy with daily oral DFP and subcutaneous DFO twice weekly is a safe and effective alternative to chelation monotherapy in β-thalassemia children. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate platelet function in patients with thalassaemia and to detect any relation to chelation treatment (deferasirox or deferiprone/deferiprone plus desferioxamine). Thirty-three transfusion-dependent patients with thalassaemia were included. The investigation consisted of aggregation testing of platelet-rich plasma by light transmission aggregometry (LTA) with the use of 5 agonists as well as the global test of haemostasis by means of the PFA-100 platelet function analyser. In 66.67% of the patients, there was reduced LTA to at least one agonist and in 18.18% there was reduced LTA to two or more agonists. The PFA-100 test was prolonged in 60.6% of the cases. An abnormal LTA and a prolonged PFA-100 time were recorded in 33.3% of the patients and 27.4% had a normal aggregation and PFA-100 test. No correlation between chelation regimen and either LTA or PFA-100 test was found. The abnormal LTA can be explained either by the release of ADP from the haemolysed red blood cells, which leads to defective platelet aggregation, or by the presence of two platelet populations. An in vitro effect without an in vivo impact could be an alternative explanation. In patients with thalassaemia, the reduced LTA and the prolonged PFA-100 closure time could be an in vitro effect and has a close correlation to the bleeding phenotype of each patient. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: We sought to define the incidence and predictive factors of pulmonary hypertension in β-thalassemia major. Methods: We studied 27 consecutive patients (19 male, 38 ± 9 years of age) with β-thalassemia major. All the patients had normal (left and right) ventricular (systolic and diastolic) function and underwent echocardiographic assessment of pulmonary artery systolic pressure. Univariate regression and discriminant function analyses were used to identify predictive factors of pulmonary hypertension. Results: Pulmonary hypertension was observed in 18.5% of the patients, but clinically significant disease was detected in only 3.7%. A total of 14 (51.8%) patients had been receiving a combined administration of deferoxamine and deferiprone for 7.0 ± 1.3 years. Amidst a large number of variables examined, ferritin levels and delayed onset of chelation therapy were the only predictors of pulmonary hypertension. Conclusion: Pulmonary hypertension in β-thalassemia major is relatively infrequent and generally mild due to improved chelation therapy. The role of hemochromatosis in pulmonary hypertension development merits further study. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The efficacy and safety of a 2-year treatment with deferasirox was evaluated in 31 patients with sickle cell anemia and transfusional iron overload. At 24 months, there were significant decreases from baseline in mean serum ferritin (from 2,344.6 to 1,986.3 μ.g/1; p = 0.040) and in mean liver iron concentration (from 13.0 ± 5.4 to 9.3 ± 5.7 mg Fe/g dry weight; p< 0.001). Myocardial T2* values were normal (>20 ms) in all patients at baseline and did not change significantly over the course of the study. However, there was a significant improvement from baseline in left ventricular ejection fraction at 24 months (62.2-64.6%; p = 0.02). Deferasirox was generally well tolerated with no progressive increases in serum creatinine or renal failure observed. These data confirm that deferasirox is effective in reducing body iron burden in patients with sickle cell anemia and transfusional iron overload. [ABSTRACT FROM AUTHOR]

There are limited studies on renal involvement in β-thalassemia, mainly involving patients on deferoxamine, reporting both glomerular and tubular dysfunction. The aim of the present study was to investigate renal involvement in young thalassemia patients, using both conventional and early markers of renal dysfunction, and to correlate findings to iron chelation therapy. Forty-two patients aged 4–23 years were studied and, for analysis purposes, were divided into two groups based on chelation therapy (group A receiving deferasirox and group B receiving deferoxamine and deferiprone combination therapy). In addition to conventional renal biochemistries, creatinine clearance, estimated glomerular filtration rate, serum cystatin C (Cys C), fractional excretion of sodium, tubular phosphorus reabsorption and urine calcium, protein, β2-microglobulin (β2-MG) and glucose levels were measured. A considerable number of patients demonstrated impaired renal function with elevated Cys C levels (36%), glomerular dysfunction with proteinuria (24%) and tubulopathy with hypercalciuria (35.5%) and elevated excretion of β2-MG (33.5%). Renal involvement seems to be present even in young patients with β-thalassemia, therefore, routine use of early markers of renal dysfunction is recommended. Further studies are needed in order to investigate the role of new chelators in tubular function parameters. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In this report we present a 37-year-old thalassemia patient with hyperferritinemia referred to our Microcytemia Center at the beginning of deferasirox (DFX) therapy. Treatment with subcutaneous infusions of desferrioxamine (DFO) had started when he was 10 years old. During the 6-month DFX treatment, serum ferritin levels progressively increased from 600 to 2,700 ng/ml despite progressive DFX dose adjustments. This paradoxically abnormal ferritin levels required drug discontinuation but were not paralleled by a similar iron burden in T2* magnetic resonance imaging. In this clinical case, ferritin levels were inappropriately increased following initiation of DFX treatment, but in the presence of an almost unmodified pattern of organ iron overload. Excluding the diagnostic dilemma of an improbable failure of DFX chelation, the pathogenesis of this phenomenon remains to be clarified, thus further complicating the problem of ferritin specificity and its role in monitoring chelation efficacy and in adapting DFX dosage in a limited period of treatment. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The monitoring of chelation therapy is a very important part of the management of transfusion-dependent patients. Classical methods of monitoring iron loading are either unreliable or unable to detect important myocardial siderosis which can predispose to the development of cardiac complications such as heart failure. The development of the T2* technique using cardiovascular magnetic resonance has allowed clinicians to have a reliable method for measuring cardiac iron to guide chelation therapy. T2* can identify early those patients who are at risk of developing cardiac complications, enabling personalised, tailored therapy to avoid potential problems. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Transfusion-induced iron overload is a frequent problem that clinicians have to face in the treatment of patients affected by both myelodysplastic syndrome (MDS) and primary myelofibrosis (PMF). Different options are currently available for chelation therapy, e.g. oral once-daily administration of the iron chelator deferasirox. In 3 patients with MDS and 1 patient with PMF, deferasirox therapy resulted in an improvement in the hemoglobin level and a reduction in transfusion dependence. Our data open new insights regarding the benefit of iron chelation therapy not only for transfusional iron overload of myelodysplastic and myelofibrotic patients but also for the increase in hemoglobin levels. The biological mechanism of action of deferasirox, an effect which is not shared by other iron chelators, is still obscure and requires further investigations Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Combined therapy with deferoxamine (DFO) and deferasirox (DFX) may be performed empirically when DFX monotherapy fails. Given the lack of published data on this therapy, the study goal was to assess the safety and efficacy of combined DFO/DFX therapy in a gerbil model. Methods: Thirty-two female Mongolian gerbils 8–10 weeks old were divided into 4 groups (sham chelated, DFO, DFX, DFO/DFX). Each received 10 weekly injections of 200 mg/kg iron dextran prior to initiation of 12 weeks of chelation. Experimental endpoints were heart and liver weights, iron concentration and histology. Results: In the heart, there was no significant difference among the treatment groups for wet-to-dry ratio, iron concentration and iron content. DFX-treated animals exhibited lower organ weights relative to sham-chelated animals (less iron-mediated hypertrophy). DFO-treated organs did not differ from sham-chelated organs in any aspects. DFX significantly cleared hepatic iron. No additive effects were observed in the organs of DFO/DFX-treated animals. Conclusions: Combined DFO/DFX therapy produced no detectable additive effect above DFX monotherapy in either the liver or heart, suggesting competition with spontaneous iron elimination mechanisms for chelatable iron. Combined therapy was well tolerated, but its efficacy could not be proven due to limitations in the animal model. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

β-Thalassemia major is a debilitating disease with a considerable incidence in Lebanon (around 2–3% carriership). The present article describes our experience to this day with 214 patients, emphasizing the survival of β-thalassemia major and development of complications among patients with different parameters. Fifteen deaths were reported. The most common cause of death was heart failure (60%). Patients with a ferritin level of 3,000 ng/ml showed better survival than those with a level >3,000 ng/ml (p < 0.006). In addition, patients with a ferritin level of 1,500 ng/ml showed less complication-free survival than those with a level >1,500 ng/ml (p < 0.024). High level of ferritin (1,500 ng/ml) is associated with increased risk of heart failure. Overall and complication-free survival were statistically different among patients classified according to birth cohort or ferritin level. The Chronic Care Center, a multidisciplinary center located in the suburbs of Beirut, led to an increase in complication-free as well as overall survival. Although patients are being diagnosed earlier and chelation therapy is being initiated at an earlier age, complications due to iron overload still persist. The introduction of new oral iron chelators and better iron overload quantitation methods will most likely modify this picture, and a follow-up study will examine their impact. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: There is increasing evidence demonstrating the value of transfusions in sickle cell disease (SCD). However, resultant iron overload can be life threatening if untreated. Chelation therapy with deferoxamine requires parenteral infusions that can negatively impact quality of life and adherence to treatment. Methods: As part of a phase II trial, SCD patient-reported outcomes were evaluated. One hundred and ninety-five patients were randomized (2:1) to receive oral deferasirox (5–30 mg/kg/day) or deferoxamine (20–50 mg/kg, 5 days per week); 121 had previously received deferoxamine. Results: At each time point, significantly more patients who had previously received deferoxamine were ‘satisfied/very satisfied’ with deferasirox, or found treatment to be ‘convenient/very convenient’ compared with deferoxamine (p < 0.001). In these patients, fewer hours were lost from daily activities with deferasirox than deferoxamine treatment. Most patients (77%) preferred deferasirox, and more were willing to continue taking deferasirox than deferoxamine at end-of-study (84 vs. 11%, respectively). Conclusions: Patients with SCD are therefore more satisfied with deferasirox, which has a lower impact on daily activities than deferoxamine. Given the high levels of satisfaction, it is likely that quality of life will be improved. These results also suggest that treatment adherence with deferasirox may be better than with deferoxamine, which should lead to improved long-term outcomes. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Twelve thalassaemia major patients have been given deferiprone 75 mg/kg body weight daily as iron chelation therapy for 5 years. Their ages ranged from 18 to 34 years (mean 24.2) at the end of the study. Two patients were hepatitis C virus (HCV) mRNA positive and a further 5 were positive for HCV antibody. The mean serum ferritin level fell significantly from 4,302 ± 2,245 μg/l SD at baseline to 3,032 ± 1,155 μg/l at 2 years (p = 0.037) and 2,229 ± 1,070 μg/l (p = 0.007) at 5 years. At the end of the study, liver iron ranged from 3.59 to 23.7 mg/g dry weight (mean 11.9 ± 5.4), 3 patients having levels >15 mg/g. There was no significant change in serum AST levels, but ALT levels fell significantly at 2 years (p = 0.019) and 5 years (p = 0.001). Liver biopsy at the end of the study showed no evidence of hepatic fibrosis caused by deferiprone. Cardiac studies showed no overall change in left ventricular ejection fraction but a significant improvement in isovolumic relaxation time (p = 0.045). We conclude that in this albeit small group of thalassaemia major patients, deferiprone was a safe long-term method of iron chelation. In a minority, higher doses of deferiprone or a combination with desferrioxamine would be needed to lower liver iron below 15 mg/g. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

With the improved life expectancy of β-thalassemia major patients, new clinical problems, such as hearing loss, must be evaluated. To determine the incidence of sensorineural hearing loss and its relationship to desferrioxamine (DFO), 128 patients receiving subcutaneous DFO in doses from 21 to 39 mg/kg/day were studied. These patients had received their total weekly dose of DFO according to two different methods. The first group (QOD group of 52%) had received it on an every other day basis. The second group (QD group of 48%) had received it on 6 days a week. Otological examinations and pure tone audiometry were performed on the patients as they routinely visited Shiraz Cooley’s Center, to find a possible correlation between the dose and duration of therapy. 56 patients (44%) in both groups had no evidence of drug-induced auditory abnormalities. Of the patients in the QOD group 44.7% had hearing loss in the right ear and 41.8% in the left ear at a frequency of 8,000 Hz compared to the QD group, 27.8 and 23%, respectively (with p < 0.047 and p < 0.02, respectively). No correlation was found between the duration of DFO therapy and sensorineural deficit. A significant correlation was found between the dose of drug given at each episode of DFO therapy and hearing loss at the frequency of 8,000 Hz, when comparing the QOD group with the QD group. Hence, it may be concluded that DFO ototoxicity is determined not only by the total amount of the drug given, but also by its maximal plasma concentration. Thus we suggest periodical audiologic checkups and a low dosage of DFO (below 50 mg/kg/day) given on at least 5–6 days a week for the prevention and prompt diagnosis of audiologic complications.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We report our experience with deferiprone (L1) (DFP) in 17 thalassemic patients, followed up in one center in Lebanon, who were initially on desferrioxamine and then shifted to DFP at a dose of 50–75 mg/kg/day as the sole chelator during 1-year follow-up. All 17 patients were compliant with therapy and there was no change in physical examination over the study period. Eight patients (47.1%) were positive for hepatitis C virus (HCV) antibodies. Urinary iron excretion was 21.8 ± 14 mg/24 h (mean ± SD) 1 week after starting DFP and dropped 12 months later to 13 ± 7.4 mg/24 h (p = 0.009, paired t test). The initial serum ferritin level was 3,863 ± 2,344 μg/l which dropped to 3,179 ± 2,075 at 12 months after starting therapy (p = 0.07). HCV-negative patients as a group exhibited a significant decrease in serum ferritin after 6 and 12 months of DFP therapy (3,942 ± 2,739 vs. 2,341 ± 1,179 and 2,681 ± 1,519 μg/l; p < 0.03 and p < 0.05, respectively). The most frequent side effects were joint pain, stiffness or swelling in 6 patients (35.3%), and nausea in 7 patients (41.2%), but these were well tolerated and did not require stopping treatment. [ABSTRACT FROM AUTHOR]

The article describes a case of homozygosity of the G320V mutation of the hepcidin or HJV genes in a 31-year-old Hungarian female patient. Information on juvenile hemachromatosis (JH) is offered. Histological examination showed that Kupffer cells and those of the liver and biliary tract were heavily laden with iron. Findings from laboratory tests and hormonal tests are elaborated. The application of regular venesections and chelation therapy is cited.

The article describes the evolution and pregnancy outcomes in women with beta-thalassemia major in Sardinia. Improvement in the management of a transfusional approach and iron chelation therapy has significantly increased the life expectancy and quality of life of patients with thalassemia. It notes that problems with hypogonadotropic hypogonadism is still associated with increased fetal and maternal complications during pregnancy.

No abstract available [ABSTRACT FROM AUTHOR]

No abstract available [ABSTRACT FROM AUTHOR]

The article explores the correct time to start iron chelation therapy (ICT) after myelodysplastic syndrome (MDS) diagnosis, focusing on a 34-year-old male with MDS who received ICT with deferasirox within the first year of diagnosis. It outlines the patient's characteristics. It has found that the patient achieved a long-term reduction in transfusion requirements and an ameliorated hemoglobin (Hb) level. It describes the impact of deferasirox on erythopoiesis.

Efforts to optimize the management of patients with β-thalassemia major (TM) continue to expand. Evidence from biomedical research evaluating safe and careful processing measures of blood products, the efficacy and safety of oral iron chelators, and noninvasive techniques for the assessment of iron overload are translated into better patient outcomes. The construction of TM management guidelines facilitated the incorporation of such evidence into practice. However, as several aspects of the management of TM remain controversial or governed by resource availability, a concern regarding potential variations in recommendations made by the different guidelines becomes rational, especially for physicians treating TM patients outside countries where the guidelines were constructed. In this work, we overview currently available guidelines for the management of TM and explore apparent similarities and differences between them. The evaluated guidelines included the Thalassaemia International Federation, US, Canadian, UK, Italian and Australian guidelines. We noted a general consensus for most aspects of management, although some guidelines provided more comprehensive and contemporary recommendations than others. We did not identify differences warranting concern, although minor differences in iron overload assessment strategy and more notable variations in the recommendations for iron chelation therapy were observed., (Copyright © 2013 S. Karger AG, Basel.)

Iron overload due to regular transfusions of packed red cells can cause multiple organ damage. Iron chelation therapy (ICT) is important in patients with aplastic anemia (AA) who require blood transfusions as supportive management. With the introduction of the oral iron chelator deferasirox, ICT has become more widely available and feasible. We studied 4 adult AA patients who had transfusion-induced iron overload and showed hematological improvement after ICT with oral deferasirox. Following deferasirox treatment, hemoglobin increased and serum ferritin levels decreased, and the patients subsequently became transfusion independent. Our experience raises the possibility of the potential benefit of ICT on hematopoiesis. Further long-term studies in larger patient cohorts are needed to clarify the effect of the restoration of hematopoiesis after iron chelation therapy., (Copyright © 2012 S. Karger AG, Basel.)

We present 2 patients with hyperferritinemia, increased liver iron and hemochromatosis-associated HFE genotypes. At diagnosis, both patients had chronic anemia that prevented initiation of phlebotomy. Iron chelation with deferasirox proved to be a safe and effective means of substantially lowering ferritin levels., (Copyright © 2011 S. Karger AG, Basel.)

Patients with beta-thalassemia often present with a restrictive pattern at pulmonary function tests (PFTs) due to several pathogenetic factors. However, the long-term evolution is unknown. We performed a longitudinal study of pulmonary function in asymptomatic, non-smoking patients with beta-thalassemia major and intermedia. We looked for temporal changes in lung function and characteristics that would predict the development of PFT abnormalities. In 1996, 18 patients with major beta-thalassemia (9 males and 9 females; age range: 18-35 years) and 11 patients with intermediate beta-thalassemia (5 males and 6 females; age range: 25-51 years) underwent clinical assessment and PFT, including body plethysmography and gas transfer study (carbon monoxide diffusion capacity, DL(CO)). Patients were reassessed in 2003. An echocardiographic evaluation was also obtained to exclude pulmonary hypertension. In 55.5% of major and 45.4% of intermediate beta-thalassemia patients, a restrictive pattern was found in 1996; in 2003 only 38.8 and 27.2% of patients, respectively, exhibited total lung capacities below the predicted values. DL(CO) was unchanged in both groups of patients, being reduced in 5 thalassemia major patients and within the normal range in intermediate patients. We conclude that asymptomatic patients with beta-thalassemia have a high prevalence of PFT abnormalities, but without significant increases over time. An improvement may be observed when good control of the iron balance is reached with optimal chelation therapy.