Ectopic calcification in ß-thalassemia patients is associated with increased oxidative stress and lower MGP carboxylation.

A number of beta-thalassemia (ß-thal) patients in the course of the disease exhibit ectopic calcification affecting skin, eyes and the cardiovascular system. Clinical and histopathological features have been described similar to those in pseudoxanthoma elasticum (PXE), although different genes are affected in the two diseases. Cultured dermal fibroblasts from ß-thal patients with and without PXE-like clinical manifestations have been compared for parameters of redox balance and for the expression of proteins, which have been already associated with the pathologic mineralisation of soft connective tissues. Even though oxidative stress is a well-known condition of ß-thal patients, our results indicate that the occurrence of mineralized elastin is associated with a more pronounced redox disequilibrium, as demonstrated by the intracellular increase of anion superoxide and of oxidized proteins and lipids. Moreover, fibroblasts from ß-thal PXE-like patients are characterized by decreased availability of carboxylated matrix Gla protein (MGP), as well as by altered expression of proteins involved in the vitamin K-dependent carboxylation process. Results demonstrate that elastic fibre calcification is promoted when redox balance threshold levels are exceeded and the vitamin K-dependent carboxylation process is affected decreasing the activity of MGP, a well-known inhibitor of ectopic calcification. Furthermore, independently from the primary gene defect, these pathways are similarly involved in fibroblasts from PXE and from ß-thal PXE-like patients as well as in other diseases leading to ectopic calcification, thus suggesting that can be used as markers of pathologic mineralisation.

Hepatocellular carcinoma in thalassaemia: an update of the Italian Registry.

The risk of developing hepatocellular carcinoma (HCC) in patients with thalassaemia is increased by transfusion-transmitted infections and haemosiderosis. All Italian Thalassaemia Centres use an ad hoc form to report all diagnoses of HCC to the Italian Registry. Since our last report, in 2002, up to December 2012, 62 new cases were identified, 52% of whom were affected by thalassaemia major (TM) and 45% by thalassaemia intermedia (TI). Two had sickle-thalassaemia (ST). The incidence of the tumour is increasing, possibly because of the longer survival of patients and consequent longer exposure to the noxious effects of the hepatotropic viruses and iron. Three patients were hepatitis B surface antigen-positive, 36 patients showed evidence of past infection with hepatitis B virus (HBV). Fifty-four patients had antibodies against hepatitis C virus (HCV), 43 of whom were HCV RNA positive. Only 4 had no evidence of exposure either to HCV or HBV. The mean liver iron concentration was 8 mg/g dry weight. Therapy included chemoembolization, thermoablation with radiofrequency and surgical excision. Three patients underwent liver transplant, 21 received palliative therapy. As of December 2012, 41 patients had died. The average survival time from HCC detection to death was 11·5 months (1·4-107·2 months). Ultrasonography is recommended every 6 months to enable early diagnosis of HCC, which is crucial to decrease mortality.

Serial echocardiographic left ventricular ejection fraction measurements: a tool for detecting thalassemia major patients at risk of cardiac death.

Cardiac damage remains a major cause of mortality among patients with thalassemia major. The detection of a lower cardiac magnetic resonance T2* (CMR-T2*) signal has been suggested as a powerful predictor of the subsequent development of heart failure. However, the lack of worldwide availability of CMR-T2* facilities prevents its widespread use for follow-up evaluations of cardiac function in thalassemia major patients, warranting the need to assess the utility of other possible procedures. In this setting, the determination of left ventricular ejection fraction (LVEF) offers an accurate and reproducible method for heart function evaluation. These findings suggest a reduction in LVEF≥7%, over time, determined by 2-D echocardiography, may be considered a strong predictive tool for the detection of thalassemia major patients with increased risk of cardiac death. The reduction of LVEF≥7% had higher (84.76%) predictive value. Finally, Kaplan-Meier survival curves of thalassemia major patients with LVEF≥7% showed a statistically significant decreased probability of survival for heart disease (p=0.0022). However, because of limitations related to the study design, such findings should be confirmed in a large long-term prospective clinical trial.

Long-term treatment with deferiprone enhances left ventricular ejection function when compared to deferoxamine in patients with thalassemia major.

Transfusion and iron chelation treatment have significantly reduced morbidity and improved survival of patients with thalassemia major. However, cardiac disease continues to be the most common cause of death. We report the left-ventricular ejection fraction, determined by echocardiography, in one hundred sixty-eight patients with thalassemia major followed for at least 5years who received continuous monotherapy with deferoxamine (N=108) or deferiprone (N=60). The statistical analysis, using the generalized estimating equations model, indicated that the group treated with deferiprone had a significantly better left-ventricular ejection fraction than did those treated with deferoxamine (coefficient 0.97; 95% CI 0.37; 1.6, p=0.002). The heart may be particularly sensitive to iron-induced mitochondrial damage because of the large number of mitochondria and its low level of antioxidants. Deferiprone, because of its lower molecular weight, might cross into heart mitochondria more efficiently, improving their activity and, thereby, myocardial cell function. Our findings indicate that the long-term administration of deferiprone significantly enhances left-ventricular function over time in comparison with deferoxamine treatment. However, because of limitations related to the design of this study, these findings should be confirmed in a prospective, randomized clinical trial.

Cardiac and hepatic iron and ejection fraction in thalassemia major: multicentre prospective comparison of combined deferiprone and deferoxamine therapy against deferiprone or deferoxamine monotherapy.

BACKGROUND: Due to the limited data available in literature, the aim of this multi-centre study was to prospectively compare in thalassemia major (TM) patients the efficacy of combined deferiprone (DFP) and deferoxamine (DFO) regimen versus either DFP and DFO in monotherapy by cardiovascular magnetic resonance (CMR) over a follow up of 18 months. METHODS: Among the first 1135 TM patients in the MIOT (Myocardial Iron Overload in Thalassemia) network, we evaluated those who had received either combined regimen (DFO + DFP, N=51) or DFP (N=39) and DFO (N=74) monotherapies between the two CMR scans. Iron overload was measured by T2* multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. RESULTS: The percentage of patients that maintained a normal global heart T2* value was comparable between DFP+DFO versus both monotherapy groups. Among the patients with myocardial iron overload at baseline, the changes in the global heart T2* and in biventricular function were not significantly different in DFP+DFO compared with the DFP group. The improvement in the global heart T2* was significantly higher in the DFP+DFO than the DFO group, without a difference in biventricular function. Among the patients with hepatic iron at baseline, the decrease in liver iron concentration values was significantly higher with combination therapy than with either monotherapy group. CONCLUSIONS: In TM patients at the dosages used in the real world, the combined DFP+DFO regimen was more effective in removing cardiac iron than DFO, and was superior in clearing hepatic iron than either DFO or DFP monotherapy. Combined therapy did not show an additional effect on heart function over DFP.

Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel.

Chelation therapy with new drugs prevents cardiac damage and improves the survival of thalassemia patients. Liver diseases have emerged as a critical clinical issue. Chronic liver diseases play an important role in the prognosis of thalassemia patients because of the high frequency of viral infections and important role of the liver in regulating iron metabolism. Accurate assessment of liver iron overload is required to tailor iron chelation therapy. The diagnosis of hepatitis B virus- or hepatitis C virus-related chronic hepatitis is required to detect patients who have a high risk of developing liver complications and who may benefit by antiviral therapy. Moreover, clinical management of chronic liver disease in thalassemia patients is a team management issue requiring a multidisciplinary approach. The purposes of this paper are to summarize the knowledge on the epidemiology and the risks of transmission of viral infections, to analyze invasive and noninvasive methods for the diagnosis of chronic liver disease, to report the knowledge on clinical course of chronic viral hepatitis, and to suggest the management of antiviral therapy in thalassemia patients with chronic hepatitis B or C virus or cirrhosis.

Long-term use of deferiprone significantly enhances left-ventricular ejection function in thalassemia major patients.

A multicenter randomized open-label long-term sequential deferiprone­deferoxamine (DFP-DFO) versus DFP alone trial (sequential DFP-DFO) performed in patients with thalassemia major (TM) was retrospectively reanalyzed to assess the variation in the left ventricular ejection fraction (LVEF) [1].

Iron chelation therapy in thalassemia major: a systematic review with meta-analyses of 1520 patients included on randomized clinical trials.

The effectiveness of deferoxamine (DFO), deferiprone (DFP), or deferasirox (DFX) in thalassemia major was assessed. Outcomes were reported as means±SD, mean differences with 95% CI, or standardized mean differences. Statistical heterogeneity was tested using χ2 (Q) and I2. Sources of bias and Grading of Recommendations Assessment, Development and Evaluation system (GRADE) were considered. Overall, 1520 patients were included. Only 7.4% of trials were free of bias. Overall measurements suggest low trial quality (GRADE). The meta-analysis suggests lower final liver iron concentrations during associated versus monotherapy treatment (p<0.0001), increases in serum ferritin levels during DFX 5, 10, and 20 mg/kg versus DFO-treated groups (p<0.00001, p<0.00001, and p=0.002, respectively), but no statistically significant difference during DFX 30 mg/kg versus DFO (p=0.70), no statistically significant variations in heart T2* signal during associated or sequential versus mono-therapy treatment (p=0.46 and p=0.14, respectively), increases in urinary iron excretion during associated or sequential versus monotherapy treatment (p=0.008 and p=0.02, respectively), and improved ejection fraction during associated or sequential versus monotherapy treatment (p=0.01 and p<0.00001, respectively). These findings do not support any specific chelation treatment. The literature shows risks of bias, and additional larger and longer trials are needed.

Deferasirox, deferiprone and desferrioxamine treatment in thalassemia major patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging.

BACKGROUND: Oral deferiprone was suggested to be more effective than subcutaneous desferrioxamine for removing heart iron. Oral once-daily chelator deferasirox has recently been made commercially available but its long-term efficacy on cardiac iron and function has not yet been established. Our study aimed to compare the effectiveness of deferasirox, deferiprone and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function in thalassemia major patients by means of quantitative magnetic resonance imaging. DESIGN AND METHODS: From the first 550 thalassemia subjects enrolled in the Myocardial Iron Overload in Thalassemia network, we retrospectively selected thalassemia major patients who had been receiving one chelator alone for longer than one year. We identified three groups of patients: 24 treated with deferasirox, 42 treated with deferiprone and 89 treated with desferrioxamine. Myocardial iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron concentrations were measured by T2* multiecho technique. RESULTS: The global heart T2* value was significantly higher in the deferiprone (34 ± 11 ms) than in the deferasirox (21 ± 12 ms) and the desferrioxamine groups (27 ± 11 ms) (P = 0.0001). We found higher left ventricular ejection fractions in the deferiprone and the desferrioxamine versus the deferasirox group (P = 0.010). Liver iron concentration, measured as T2* signal, was significantly lower in the desferrioxamine versus the deferiprone and the deferasirox group (P = 0.004). CONCLUSIONS: The cohort of patients treated with oral deferiprone showed less myocardial iron burden and better global systolic ventricular function compared to the patients treated with oral deferasirox or subcutaneous desferrioxamine.

Malignancies in ß-thalassemia patients: first description of two cases of thyroid cancer and review of the literature.

ß-Thalassemias are a group of hereditary blood disorders characterized by abnormalities in the synthesis of the ß hemoglobin (Hb) chains. This disease causes excessive storage of iron in all organs and endocrine glands. Treatment of ß-thalassemia major (ß-TM) consists of regular blood transfusions, iron chelation and management of secondary complications of iron overload. Endocrine abnormalities are frequently observed. In the last 25 years, the clinical picture of the disease has changed progressively thanks to improvement of treatments. Today, the majority of thalassemic patients reach adult age. The better prognosis and the longer lifespan of affected patients could be responsible for the susceptibility to other concomitant diseases which can manifest during their life. In this context, the possibility and recent literature reports about some cases of malignancy in thalassemic patients open new scenarios for oncoming years. We describe first reports of endocrine malignancies in thalassemic patients.

Sequential alternating deferiprone and deferoxamine treatment compared to deferiprone monotherapy: main findings and clinical follow-up of a large multicenter randomized clinical trial in -thalassemia major patients.

In ß-thalassemia major (ß-TM) patients, iron chelation therapy is mandatory to reduce iron overload secondary to transfusions. Recommended first line treatment is deferoxamine (DFO) from the age of 2 and second line treatment after the age of 6 is deferiprone (L1). A multicenter randomized open-label trial was designed to assess the effectiveness of long-term alternating sequential L1-DFO vs. L1 alone iron chelation therapy in ß-TM patients. Deferiprone 75 mg/kg 4 days/week and DFO 50 mg/kg/day for 3 days/week was compared with L1 alone 75 mg/kg 7 days/week during a 5-year follow-up. A total of 213 thalassemia patients were randomized and underwent intention-to-treat analysis. Statistically, a decrease of serum ferritin level was significantly higher in alternating sequential L1-DFO patients compared with L1 alone patients (p = 0.005). Kaplan-Meier survival analysis for the two chelation treatments did not show statistically significant differences (log-rank test, p = 0.3145). Adverse events and costs were comparable between the groups. Alternating sequential L1-DFO treatment decreased serum ferritin concentration during a 5-year treatment by comparison to L1 alone, without significant differences of survival, adverse events or costs. These findings were confirmed in a further 21-month follow-up. These data suggest that alternating sequential L1-DFO treatment may be useful for some ß-TM patients who may not be able to receive other forms of chelation treatment.

Increased survival and reversion of iron-induced cardiac disease in patients with thalassemia major receiving intensive combined chelation therapy as compared to desferoxamine alone.

Myocardial iron overload is the leading cause of death in patients with beta-thalassemia major. An intensification monotherapy with deferoxamine (DFO) as well as a combination therapy with DFO and deferiprone (DFP) reduces myocardial iron and improves cardiac function. However, the prognosis for thalassemia major patients with established cardiac disease switched from DFO monotherapy to combined DFP/DFO chelation is unknown. Twenty-eight thalassemia major patients with cardiac disease were enrolled in a prospective study lasting 42+/-6 months. Fifteen (9 high-ferritin and 6 low-ferritin) were placed on DFP/DFO (DFP, 75 mg/kg t.i.d.; DFO, 40-50mg/kg over 8-12h at night 5-7 days/week), while 13 (5 high- and 8 low-ferritin) received DFO alone. No cardiac events were observed among high-ferritin patients on combination therapy, whereas 4 cardiac events (p=0.0049), including three deaths, occurred in high-ferritin patients on DFO monotherapy. These findings demonstrate that in thalassemia major patients with well-established cardiac disease combined iron-chelation therapy with DFP/DFO is superior to DFO monotherapy.

Long-term sequential deferiprone-deferoxamine versus deferiprone alone for thalassaemia major patients: a randomized clinical trial.

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.

Improving survival with deferiprone treatment in patients with thalassemia major: a prospective multicenter randomised clinical trial under the auspices of the Italian Society for Thalassemia and Hemoglobinopathies.

The prognosis for thalassemia major has dramatically improved in the last two decades. However, many transfusion-dependent patients continue to develop progressive accumulation of iron. This can lead to tissue damage and eventually death, particularly from cardiac disease. Previous studies that investigated iron chelation treatments, including retrospective and prospective non-randomised clinical trials, suggested that mortality, due mainly to cardiac damage, was reduced or completely absent in patients treated with deferiprone (DFP) alone or a combined deferiprone-deferoxamine (DFP-DFO) chelation treatment. However, no survival analysis has been reported for a long-term randomised control trial. Here, we performed a multicenter, long-term, randomised control trial that compared deferoxamine (DFO) versus DFP alone, sequential DFP-DFO, or combined DFP-DFO iron chelation treatments. The trial included 265 patients with thalassemia major, with 128 (48.3%) females and 137 (51.7%) males. No deaths occurred with the DFP-alone or the combined DFP-DFO treatments. One death occurred due to graft versus host disease (GVHD) in a patient that had undergone bone marrow transplantation; this patient was censored at the time of transplant. Only one death occurred with the DFP-DFO sequential treatment in a patient that had experienced an episode of heart failure one year earlier. Ten deaths occurred with the deferoxamine treatment. The main factors that correlated with an increase in the hazard ratio for death were: cirrhosis, arrhythmia, previous episode of heart failure, diabetes, hypogonadism, and hypothyroidism. In a Cox regression model, the interaction effect of sex and age was statistically significant (p-value<0.013). For each increasing year of age, the hazard ratio for males was 1.03 higher than that for females (p-value<0.013). In conclusion, the results of this study show that the risk factors for predicting mortality in patients with thalassemia major are deferoxamine-treatment, complications, and the interaction effect of sex and age.

Improved T2* assessment in liver iron overload by magnetic resonance imaging.

In the clinical MRI practice, it is common to assess liver iron overload by T2* multi-echo gradient-echo images. However, there is no full consensus about the best image analysis approach for the T2* measurements. The currently used methods involve manual drawing of a region of interest (ROI) within MR images of the liver. Evaluation of a representative liver T2* value is done by fitting an appropriate model to the signal decay within the ROIs vs. the echo time. The resulting T2* value may depend on both ROI placement and choice of the signal decay model. The aim of this study was to understand how the choice of the analysis methodology may affect the accuracy of T2* measurements. A software model of the iron overloaded liver was inferred from MR images acquired from 40 thalassemia major patients. Different image analysis methods were compared exploiting the developed software model. Moreover, a method for global semiautomatic T2* measurement involving the whole liver was developed. The global method included automatic segmentation of parenchyma by an adaptive fuzzy-clustering algorithm able to compensate for signal inhomogeneities. Global liver T2* value was evaluated using a pixel-wise technique and an optimized signal decay model. The global approach was compared with the ROI-based approach used in the clinical practice. For the ROI-based approach, the intra-observer and inter-observer coefficients of variation (CoVs) were 3.7% and 5.6%, respectively. For the global analysis, the CoVs for intra-observers and inter-observers reproducibility were 0.85% and 2.87%, respectively. The variability shown by the ROI-based approach was acceptable for use in the clinical practice; however, the developed global method increased the accuracy in T2* assessment and significantly reduced the operator dependence and sampling errors. This global approach could be useful in the clinical arena for patients with borderline liver iron overload and/or requiring follow-up studies.

Pain syndromes in sickle cell disease: an update.

OBJECTIVE: Pain has a critical role in the management of sickle cell disease (SCD). Patients may suffer from several pain syndromes, which may be or not may be associated with other clinical complications, such as anemia, organ failures, and infections. DESIGN: Data for review were identified by using PubMed to search MEDLINE, limiting the search to abstract/articles in English, Italian, French, and Dutch. The key words pain, sickle cell disease, anemia, hemoglobin, hemoglobinopathy, analgesics, opioids, morphine, acetaminophen, paracetamol, nonsteroidal anti-inflammatory drugs, hematology, and quality of life were variously combined in the title, abstract, and key word search list. The abstract database of most hematological congresses and the bibliographies of most relevant articles were also considered. RESULTS: There are two major types of SCD pain: acute and chronic. Sometimes, mixed and neuropathic pain can be also observed. Acute pain is mostly related to vaso-occlusion. Chronic pain may be due to some SCD complications, such as leg ulcers and avascular necrosis. CONCLUSIONS: Pain management in the SCD setting needs multidisciplinary approaches, given the several syndromes and the pathogenic mechanisms that are likely involved. Pain management is not standardized and often difficult, so that many patients with SCD are still poorly treated. Further efforts to develop care plans and treatment protocols as well as management guidelines are required.

Giant symptomatic myelolipoma of the right adrenal gland: a case report.

Adrenal myelolipoma is an uncommon tumour of the adrenal gland, usually unilateral, frequently associated with hypertension and obesity, with a benign biological behaviour and without hormonal activity, first described in 1905. The neoplasm consists of adipose tissue and myelopoietic cells of the bone marrow. These tumours have a very slow but continued growth and their volume and weight vary significantly from small lesions of a few grams to huge masses weighing up to several kilograms. If symptoms occur, surgery should be performed without delay, especially for large myelolipomas that are at high risk of spontaneous rupture with haemorrhage and life-threatening shock. In this report a case of a 43-year-old male with a 22 x 18 x 9 cm giant myelolipoma, weighing 3500 g and originating from the right adrenal gland is described. The large mass dislocating and compressing the inferior vena cava, was removed surgically. The early postoperative course and the late outcome were favourable without recurrence after 30 months. The different aetiological hypotheses of this rare neoplasm and its clinical features, diagnosis and treatment are discussed.

[Laparoscopic splenectomy in haematological diseases: short- and medium-term results in thirty initial cases]. / La splenectomia laparoscopica nelle patologie ematologiche: risultati a breve e medio terrnine in trenta casi iniziali.

In 1991 Delaitre and Maignien described the first laparoscopic splenectomy, since when a rapid spread of this technique has been observed and the procedure has become the gold standard in the surgical management of benign and malignant haematological diseases. In the present study, the results of the first 30 laparoscopic splenectomies performed at the Division of General Surgery of the S. Eugenio Hospital of Rome are reported. The operations were performed in patients with benign (27 cases) and malignant (3 cases) haematological diseases, treated in the Regional Haematological Centre of the same hospital. The procedures were carried out according to criteria corresponding to those recently described in the guidelines of the European Association for Endoscopic Surgery. As regards the results, two procedures (6.7%) were converted to open surgery. One postoperative haemorrhage was observed, requiring a laparoscopic reoperation for haemostasis. No other major local or general complications were observed. Mortality was nil. The mean postoperative hospital stay was 4.2 days (range: 4-8 days). Medium-term surgical and haematological results were excellent. Laparoscopic splenectomy is the surgical gold standard, but should be performed in advanced centres in close cooperation with a haematology centre. The procedure is indicated in all patients who are candidates for splenectomy, with the sole exception of those affected by portal hypertension or with general contraindications to laparoscopy. In advanced centres, better early and late results can be achieved, in addition to the well-known benefits of the minimally invasive technique, particularly in aesthetic terms, which in younger patients affected by benign haematological pathologies are very important.

Anemia in beta-thalassemia patients targets hepatic hepcidin transcript levels independently of iron metabolism genes controlling hepcidin expression.

Thalassemia associates anemia and iron overload, two opposite stimuli regulating hepcidin gene expression. We characterized hepatic hepcidin expression in 10 thalassemia major and 13 thalassemia intermedia patients. Hepcidin mRNA levels were decreased in the thalassemia intermedia group which presented both lower hemoglobin and higher plasma soluble transferrin receptor levels. There was no relationship between hepcidin mRNA levels and those of genes controlling iron metabolism, including HFE, hemojuvelin, transferrin receptor-2 and ferroportin. These results underline the role of erythropoietic activity on hepcidin decrease in thalassemic patients and suggest that mRNA modulations of other studied genes do not have a significant impact.

Treatment of iron overload in thalassemia.

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.