Search results for "thalassaemia"

Evidence for Three Distinct Classes of Phenotype Severity in Beta-Thalassaemia

2019

Background: Classification of phenotype severity in patients with beta-thalassaemia has so far relied mainly on expert opinion using parameters of genotype, clinical features at diagnosis, and transfusion requirement. The aim of this study was to use a large dataset of patients with beta-thalassaemia and evaluate a classification system based on onset variables agreed on by an international expert group, including age at diagnosis, at first transfusion, and at first iron chelation. Methods: A retrospective dataset of 7910 patients with homozygous or compound heterozygous beta-thalassaemia was used and subjected to cluster and classification analysis starting with the onset variables. Result…

A complication risk score to evaluate clinical severity of thalassaemia syndromes

2020

The thalassaemia syndromes (TS) show different phenotype severity. Developing a reliable, practical and global tool to determine disease severity and tailor treatment would be of great value. Overall, 7910 patients were analysed with the aim of constructing a complication risk score (CoRS) to evaluate the probability of developing one or more complications. Nine independent variables were included in the investigation as predictors. Logistic regression models were used for Group A [transfusion-dependent thalassaemia (TDT)], Group B [transfused non-TDT (NTDT)] and Group C (non-transfused NTDT). Statistically significant predictors included age (years), haemoglobin levels, hepatic transaminas…

Hepatocellular carcinoma in patients with thalassaemia syndromes: clinical characteristics and outcome in a long term single centre experience

2010

Noninvasive assessment of liver fibrosis in thalassaemia major patients by transient elastography (TE) - lack of interference by iron deposition.

2009

The correlation between liver stiffness, measured by transient elastography, liver fibrosis, using the histological METAVIR score, and iron overload, measured by atomic absorption spectrometry was evaluated in 56 homozygous-b-thalassaemics. Liver stiffness increased proportionally to liver fibrosis staging (r = 0Æ70; P > 0Æ001) independently of liver iron concentration (r = 0Æ01; P = 0Æ932). The area under the receiver-operating characteristic curve for prediction of cirrhosis was 0Æ997 (95% confidence interval [CI]: 0Æ925–1Æ000) with cut-off of 13 kPa with 100% sensitivity (95% CI: 69Æ0–100Æ0) and 95% specificity (95% CI: 84Æ2–99Æ3). Transient elastography is a reliable non-invasive tool f…

Hypogonadism and Hormone Replacement Therapy on Bone Mass of Adult Women with Thalassemia Major

2002

We studied bone mass and metabolism in 30 adult women (age 28.5 +/- 1.3) with thalassemia major (TM) and evaluated whether prolonged hormone replacement therapy (HRT) was able to optimize bone accrual. TM patients had reduced bone mass, increased bone turnover and lower serum gonadotropin and estradiol levels compared with 10 normal women of similar age. A significant correlation was found between bone mass and sex hormone levels. Six TM patients with normal ovarian function had normal bone turnover markers and modestly low bone mass (lumbar spine -1.29 +/- 0.31; femoral neck -0.60+/-0.21; Z-score). The other 24 TM women were hypogonadic and had significantly lower bone mass for age (lumbar…

Iron Chelation Therapy in thalassaemia major: a sistematic review with meta-analyses of 1520 patients included on randomized clinical trials

2011

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, 1…

Primary HBB gene mutation severity and long-term outcomes in a global cohort of β-thalassaemia

2021

In β-thalassaemia, the severity of inherited β-globin gene mutations determines the severity of the clinical phenotype at presentation and subsequent transfusion requirements. However, data on associated long-term outcomes remain limited. We analysed data from 2109 β-thalassaemia patients with available genotypes in a global database. Genotype severity was grouped as β0 /β0 , β0 /β+ , β+ /β+ , β0 /β++ , β+ /β++ , and β++ /β++ . Patients were followed from birth until death or loss to follow-up. The median follow-up time was 34·1 years. Mortality and multiple morbidity outcomes were analyzed through five different stratification models of genotype severity groups. Interestingly, β0 and β+ mu…

Long-term sequential deferiprone-deferoxamine versus deferiprone alone for thalassemia major patients: a randomised clinical trial

2009

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…

HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia

2014

International audience; β-Thalassaemia major (β-TM) is an inherited haemoglobinopathy caused by a quantitative defect in the synthesis of β-globin chains of haemoglobin, leading to the accumulation of free α-globin chains that form toxic aggregates. Despite extensive knowledge of the molecular defects causing β-TM, little is known of the mechanisms responsible for the ineffective erythropoiesis observed in the condition, which is characterized by accelerated erythroid differentiation, maturation arrest and apoptosis at the polychromatophilic stage. We have previously demonstrated that normal human erythroid maturation requires a transient activation of caspase-3 at the later stages of matur…

Improvement of heart iron with preserved patterns of iron store by CMR-guided chelation therapy

2014

[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…