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

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…

Prospective Comparison on Cardiac Iron and Liver Iron by MR In Thalassemia Major Patients Treated with Combination Deferipron–Desferrioxamine Versus Deferipron and Desferrioxamine In Monoterapy

Abstract Abstract 5164 Introduction: Using T2* MR a randomised placebo controlled study from Sardinia demonstrated combination therapy with deferiprone and desferrioxamine (DFP+DFO) significantly more effective than DFO in improving myocardial iron. One non-randomised study from Sardinia and one observational study from Greece seem to confirm for DFP+DFO therapy the most rapid clearance of cardiac iron. No data are available in literature about prospective comparisons on cardiac iron and function and liver iron in TM patients treated with DFP+DFO versus DFP and DFO in monotherapy. The aim of this multi-centre study was to assess prospectively in a large clinical setting the efficacy of the …

A complication risk score to evaluate clinical severity of thalassaemia syndromes

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…

Development of a Severity Score System for Thalassemia Syndromes

Introduction Thalassemia Syndromes (TS) are a group of inherited haemoglobin disorders characterized by different phenotype severity falling among heterozygote state, no transfusion dependent thalassemia (NTDT) and transfusion dependent Thalassemia (TDT) (Graffeo et al, 2018; Taher & Saliba, 2017). Several factors, independently by genotype and globin chain unbalance, modulate the severity of ineffective erythropoiesis (Rivella et al, 2015). Considering the complexity of this pathophysiology, one tool to evaluate patients on an individual basis is needed. The aim of this study was to develop a severity scoring system with a view to initiate timely interventions that would prevent any fu…

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…

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

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…

Survival and causes of death in 2,033 patients with non-transfusion-dependent β-thalassemia

Risk of mortality from anemia and iron overload in nontransfusion-dependent β-thalassemia

Three Distinct Groups of Phenotype Severity in Beta-Thalassemia

Background Thalassemia Syndromes (TS) are commonly classified as transfusion-dependent-thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT) at diagnosis on the basis of requirement for lifelong regular transfusion therapy for survival. However, data from observational studies and expert opinion suggest that these categories may reflect a wide spectrum rather than a dichotomy, and may actually be interchangeable at many parts of the disease journey. Thus, an evaluation of alternate clusters to classify TS patients remains of merit. Aims The aim of this study was to cluster TS patients on the basis of possible clinical indicators of phenotype severity (IPhS) using suitable algori…