0000000000003127
AUTHOR
Vincenzo Caruso
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 …
Different patterns of myocardial iron distribution by whole-heart T2* magnetic resonance as risk markers for heart complications in thalassemia major.
Background The multislice multiecho T2* cardiovascular magnetic resonance (CMR) technique allows to detect different patterns of myocardial iron overload (MIO). The aim of this cross-sectional study was to verify the association between cardiac complications (heart failure and arrhythmias), biventricular dysfunction and myocardial fibrosis with different patterns of MIO in thalassemia major (TM) patients. Methods We considered 812 TM patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. The T2* value in all the 16 cardiac segments was evaluated. Results We identified 4 groups of patients: 138 with homogeneous MIO (all segments with T2* < 20 ms), 97 with heterogene…
Multicenter validation of the magnetic resonance t2* technique for segmental and global quantification of myocardial iron
Purpose To assess the transferability of the magnetic resonance imaging (MRI) multislice multiecho T2* technique for global and segmental measurement of iron overload in thalassemia patients. Materials and Methods Multiecho T2* sequences were installed on six MRI scanners. Five healthy subjects (n = 30) were scanned at each site; five thalassemia major (TM) patients were scanned at the reference site and were rescanned locally (n = 25) within 1 month. T2* images were analyzed using previously validated software. Results T2* values of healthy subjects showed intersite homogeneity. On TM patients, for global heart T2* values the correlation coefficient was 0.97, coefficients of variation (CoV…
Long-Term Use of Deferiprone Enhances Significantly the Left Ventricular Ejection Function in Thalassemia Major
Abstract Abstract 5302 Background: A multicentre randomized controlled trial (RCT) was designed to assess the effectiveness of long-term sequential deferiprone-deferoxamine (DFO-DFP) versus DFP alone to treat thalassaemia major (TM) (Maggio et al.,2009). Effectviness, survival, adverse events and costs were comparable between the groups. These findings were confirmed in a further 21-month follow-up (Pantalone et al., 2011). Moreover, deferiprone-alone has been reported to be superior to deferoxamine for the removal of cardiac iron and improvement in left ventricular ejection function (LVEF). However, little is known of its relative effect on LVEF after long-term treatment. Therefore, data f…
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 qua…
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 thalasse…
Long-term sequential deferiprone-deferoxamine versus deferiprone alone for thalassemia major patients: a randomised 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…
Repeated Echocardiographic Left Ventricular Ejection Fraction Measurements: A Strong and Accessible Tool for Detecting At High Risk of Heart Failure Thalassemia Major Population
Abstract Abstract 3197 Background: The prognosis for thalassemia major (TM) has dramatically improved in the last two decades. However, many transfusion-dependent patients continue to develop secondary iron overloading, and eventually death, particularly from cardiac disease. The possibility of detecting easily and earliest the patients at risk of cardiac death is so far the main challenge of clinical management of these patients. Therefore, the mean reduction of Left Ventricular Ejection Fraction (LVEF), determined by echocardiography, was evaluated over the time. Methods: Among the 413 observed patients only 188 had complete records for LVEF measurements during, at least, five considered …
Dual therapy with peg-interferon and ribavirin in thalassemia major patients with chronic HCV infection: Is there still an indication?
Background: Iron overload and hepatitis C virus (HCV) infection together can lead to chronic liver damage in thalassemia major (TM) patients. Aims: We investigated viral, genetic, and disease factors influencing sustained virological response (SVR) after peg-interferon and ribavirin therapy in TM patients with HCV infection. Methods: We analyzed 230 TM patients with HCV infection (mean age 36.0 ± 6.3 years; 59.1% genotype 1; 32.2% genotype 2; 3.4% genotype 3; and 5.3% genotype 4; 28.7% carried CC allele of rs12979860 in IL28B locus; 79.6% had chronic hepatitis and 20.4% cirrhosis; 63.5% naive and 36.5% previously treated with interferon alone) treated in 14 Italian centers. Results: By mul…
Single region of interest versus multislice T2* MRI approach for the quantification of hepatic iron overload.
Purpose To evaluate the effectiveness of the single ROI approach for the detection of hepatic iron burden in thalassemia major (TM) patients in respect to a whole liver measurement. Materials and Methods Five transverse hepatic slices were acquired by a T2* gradient-echo sequence in 101 TM patients and 20 healthy subjects. The T2* value was calculated in a single region of interest (ROI) defined in the medium-hepatic slice. Moreover, the T2* value was extracted on each of the eight ROIs defined in the functionally independent segments. The mean hepatic T2* value was calculated. Results For patients, the mean T2* values over segments VII and VIII were significantly lower. This pattern was su…
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 β-thalassemia major (β-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 versus L1 alone iron chelation therapy in β-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 5-year follow-up. A total of 213 thalassemia patients were randomized and underwent intention-to-treat analysis. Statisticall…
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 sixtyeight patients with thalassemia major followed for at least 5 years 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 (c…
Hepatitis B virus in diabetic patients
The presence of HBV markers was determined in 149 serum samples obtained from diabetic patients and was compared with a normal population. Diabetics have the same incidence of HBsAg but significantly higher anti-HBc antibodies. These differences were seen in the group of diabetics on oral hypoglycemic therapy. These results cannot yet be explained.
A T2* MRI Prospective Survey on Heart and Liver Iron In Thalassemia Major Patients Treated with Deferasirox Versus Deferiprone and Desferrioxamine In Monotherapy.
Abstract Abstract 4267 Introduction: Most deaths in thalassemia major (TM) result from cardiac complications due to iron overload. In thalassaemia available three iron chelation regimes in monotherapy may achieve different changes in cardiac iron and function and liver iron. No data are available in literature about prospective comparisons on cardiac iron and function and liver iron in TM patients treated with deferasirox (DFX) versus deferiprone (DFP) and desferrioxamine (DFO) in monotherapy. Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluated quantitatively this issue. The aim of this multi-centre study was to assess prospectively in the clinical practice th…
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%, ov…
Long-term use of deferiprone significantly enhances left-ventricular ejection function in thalassemia major patients
A multicenter randomized open-label long-term sequential deferiprone–deferoxamine (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].