0000000000003133
AUTHOR
Domenico Giuseppe D'ascola
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 …
Preferential patterns of myocardial iron overload by multislice multiecho T2* CMR in thalassemia major patients.
T*(2) multislice multiecho cardiac MR allows quantification of the segmental distribution of myocardial iron overload. This study aimed to determine if there were preferential patterns of myocardial iron overload in thalassemia major. Five hundred twenty-three thalassemia major patients underwent cardiac MR. Three short-axis views of the left ventricle were acquired and analyzed using a 16-segment standardized model. The T*(2) value on each segment was calculated, as well as the global value. Four main circumferential regions (anterior, septal, inferior, and lateral) were defined. Significant segmental variability was found in the 229 patients with significant myocardial iron overload (glob…
Treatment of hepatitis C virus infection with direct-acting antiviral drugs is safe and effective in patients with hemoglobinopathies
Progression of liver fibrosis in patients with hemoglobinopathies is strongly related to the severity of iron overload and the presence of chronic hepatitis C virus (HCV) infection. Effective iron chelation therapy and HCV infection eradication may prevent liver complications. The European Association for the Study of the Liver guidelines recommend interferon-free regimens for the treatment of HCV infection in patients with hemoglobinopathies. However, data regarding the use of direct-acting antiviral drugs (DAAs) in this patient population are few. This observational study evaluated the safety and efficacy of therapy with DAAs in an Italian cohort of patients with hemoglobinopathies, chron…
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…
Myocardial fibrosis by delayed enhancement cardiovascular magnetic resonance and HCV infection in thalassemia major patients
ss Open Acce Oral presentation Myocardial fibrosis by delayed enhancement cardiovascular magnetic resonance and HCV infection in thalassemia major patients Alessia Pepe1, Antonella Meloni1, Zelia Borsellino2, Maria Chiara Dell'Amico1, Vincenzo Positano1, Caterina Borgna-Pignatti3, Aurelio Maggio4, Gennaro Restaino5, Francesco Gagliardotto2, Paolo Cianciulli6, Luciano Prossomariti7, Aldo Filosa7, Michele Centra8, Domenico D'Ascola9, Antonella Quarta10, Angelo Peluso11, Antonello Pietrangelo12, Eliana Cracolici13, Massimo Lombardi*1 and Marcello Capra2
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…
Transfusion Therapy in a Multi-Ethnic Sickle Cell Population Real-World Practice. a Preliminary Data Analysis of Multicentre Survey
Abstract Introduction. Despite the increasing of number of patients with Sickle Cell Disease (SCD) in Italy, due to multi-ethnic migratory phenomena, a large percentage of Caucasian sickle population is already present in Italy mainly with b-thal/HbS genotype. Red cell transfusion is one effective treatment for both acute and chronic complications of SCD, while hydroxycarbamide (HC) is used to reduce the frequency of painful vaso-occlusive crises (VOCs) and decrease the need for blood transfusion. Through the National Comprehensive Reference Centers for SCD, the Italian Society of Thalassemia and Hemoglobinopathies (SITE), in collaboration with the Society Italian Transfusion Medicine and I…
Safety and Efficacy of Direct-Acting Antiviral Drugs in Patients with Haemoglobinophaties and Chronic Hepatitis C Infection
Abstract Background and Aim: Direct-acting antiviral drugs (DAAs) have a very high efficacy in patients with hepatitis C virus (HCV) infection, but they have not been extensively used in patients with haemoglobinophaties. To evaluate the safety and efficacy of DAA regimens in this subset we used the ITHACA-SITE dataset, which includes patients with haemoglobinophaties and chronic HCV liver disease treated in Italy. Patients and methods: Between March 2015 and June 2016, 121 patients included in the ITHACA-SITE dataset started DAA regimens. Cirrhosis was defined by FibroScan®showing≥12 kPa performed within 6 months before the treatment. Regimen choice and use of ribavirin were based on viral…
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…
Deferiprone versus deferoxamine in patients with thalassemia major: a randomized clinical trial.
Deferiprone has been suggested as an effective oral chelation therapy for thalassemia major. To assess its clinical efficacy, we compared deferiprone with deferoxamine in a large multicenter randomized clinical trial. One-hundred forty-four consecutive patients with thalassemia major and serum ferritin between 1500 and 3000 ng/ml were randomly assigned to deferiprone (75 mg/kg/day) (n = 71) or deferoxamine (50 mg/kg/day) (n = 73) for 1 year. The main measure of efficacy was the reduction of serum ferritin. Liver and heart iron contents were assessed by magnetic resonance. Liver iron content and fibrosis stage variations were assessed on liver biopsy by the Ishak score in all patients willin…
Improvement of heart iron with preserved patterns of iron store by CMR-guided chelation therapy
[Formula: see text] multislice multiecho cardiac magnetic resonance (CMR) allows quantification of the segmental distribution of myocardial iron overload (MIO). We evaluated whether a preferential pattern MIO was preserved between two CMR scans in regularly chelated thalassaemia major (TM) patients.We evaluated prospectively 259 TM patients enrolled in the MIO in Thalassaemia (MIOT) network with a CMR follow-up (FU) study at 18 ± 3 months and significant MIO at baseline. The [Formula: see text] in the 16 segments and the global value were calculated. Four main circumferential regions (anterior, septal, inferior and lateral) were defined. We identified two groups: severe (n = 80, global [For…