Betibeglogene autotemcel gene therapy in patients with transfusion-dependent, severe genotype β-thalassaemia (HGB-212): a non-randomised, multicentre, single-arm, open-label, single-dose, phase 3 trial.

Background: Transfusion-dependent β-thalassaemia (TDT) is a severe disease, resulting in lifelong blood transfusions, iron overload, and associated complications. Betibeglogene autotemcel (beti-cel) gene therapy uses autologous haematopoietic stem and progenitor cells (HSPCs) transduced with BB305 lentiviral vector to enable transfusion independence.

Methods: HGB-212 was a non-randomised, multicentre, single-arm, open-label, phase 3 study of beti-cel in patients with TDT conducted at eight centres in France, Germany, Greece, Italy, the UK, and the USA.

Hemoglobin Balkh, a Novel Mutation in Codon 132 of α2-Globin Gene [α132(H15) (+T) or :C.396dup (p.Val134fs)]: A Case Report and Insight into the Pathophysiology.

We report a novel mutation on α2-globin gene leading to an elongated α-chain. This novel frameshift mutation was detected in a 13-year-old boy from Balkh province, Afghanistan. DNA analysis identified an insertion of thymine (T) at codon 132 [:c.

Disease burden, management strategies, and unmet needs in α-thalassemia due to hemoglobin H disease.

Alpha-thalassemia is an inherited blood disorder caused by impaired α-globin chain production, leading to anemia and other complications. Hemoglobin H (HbH) disease is caused by a combination of mutations generally affecting the expression of three of four α-globin alleles; disease severity is highly heterogeneous, largely driven by genotype. Notably, non-deletional mutations cause a greater degree of ineffective erythropoiesis and hemolysis, higher transfusion burden, and increased complication risks versus deletional mutations.

Non-invasive prenatal testing of beta-hemoglobinopathies using next generation sequencing, in-silico sequence size selection, and haplotyping.

Aim: To develop a non-invasive prenatal test for beta-hemoglobinopathies based on analyzing maternal plasma by using next generation sequencing.

Methods: We applied next generation sequencing (NGS) of maternal plasma to the non-invasive prenatal testing (NIPT) of autosomal recessive diseases, sickle cell disease and beta-thalassemia. Using the Illumina MiSeq, we sequenced plasma libraries obtained via a Twist Bioscience probe capture panel covering 4 Kb of chromosome 11, including the beta-globin (HBB) gene and >450 genomic single-nucleotide polymorphisms (SNPs) used to estimate the fetal fraction (FF).

Relationships among Physical Activity, Pain, and Bone Health in Youth and Adults with Thalassemia: An Observational Study.

Patients with thalassemia (Thal) engage in less physical activity than non-Thal populations, which may contribute to pain and osteoporosis. The purpose of this study was to assess relationships between physical activity, pain, and low bone mass in a contemporary sample of patients with Thal. Seventy-one patients with Thal (50 adults ≥18 years, 61% male, 82% transfusion-dependent) completed the Brief Pain Inventory Short Form and validated physical activity questionnaires for youth and adults.

The Clinical Phenotypes of Alpha Thalassemia.

Clinical manifestations of α-thalassemia range from no symptoms to severe transfusion-dependent anemia. Alpha thalassemia trait is deletion of 1 to 2 α-globin genes, whereas α-thalassemia major (ATM; Barts hydrops fetalis) is the deletion all 4 α genes. All other genotypes of intermediate severity are categorized as HbH disease, a vastly heterogenous group.

Safety and efficacy of mitapivat, an oral pyruvate kinase activator, in adults with non-transfusion dependent α-thalassaemia or β-thalassaemia: an open-label, multicentre, phase 2 study.

Background: Patients with non-transfusion-dependent thalassaemia (NTDT), although they do not require regular blood transfusions for survival, can still accrue a heavy burden of comorbidities. No approved disease-modifying therapies exist for these patients. We aimed to investigate the safety and efficacy of mitapivat (Agios Pharmaceuticals, Cambridge, MA, USA), a pyruvate kinase activator, in adults with non-transfusion-dependent (NTD) α-thalassaemia or NTD β-thalassaemia.

Betibeglogene Autotemcel Gene Therapy for Non-β/β Genotype β-Thalassemia.

Background: Betibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent β-thalassemia contains autologous CD34+ hematopoietic stem cells and progenitor cells transduced with the BB305 lentiviral vector encoding the β-globin (β) gene.

Methods: In this open-label, phase 3 study, we evaluated the efficacy and safety of beti-cel in adult and pediatric patients with transfusion-dependent β-thalassemia and a non-β/β genotype. Patients underwent myeloablation with busulfan (with doses adjusted on the basis of pharmacokinetic analysis) and received beti-cel intravenously.

Noninvasive Prenatal Test for β-Thalassemia and Sickle Cell Disease Using Probe Capture Enrichment and Next-Generation Sequencing of DNA in Maternal Plasma.

Background: Noninvasive prenatal testing (NIPT) of chromosomal aneuploidies based on next-generation sequencing (NGS) analysis of fetal DNA in maternal plasma is well established, but testing for autosomal recessive disorders remains challenging. NGS libraries prepared by probe capture facilitate the analysis of the short DNA fragments plasma. This system has been applied to the β-hemoglobinopathies to reduce the risk to the fetus.

Nutrition in Thalassemia: A Systematic Review of Deficiency, Relations to Morbidity, and Supplementation Recommendations.

Background: Reports of nutritional deficiencies in patients with thalassemia (Thal) are common. Despite its importance, however, nutritionally focused research in Thal has been limited by inadequate sample size, inconsistent methodology, a lack of control comparisons, and few interventional trials. Due to these limitations, clinicians lack evidence-based nutrition recommendations to support clinical decision-making.

Pituitary iron and factors predictive of fertility status in transfusion dependent thalassemia.

Not available.

A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia.

Background: Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients.

Methods: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.

Thalassemia: Common Clinical Queries in Management.

Beta thalassemia major (TM) is the most frequent form of transfusion-dependent inherited anemia in India. The thalassemia syndromes exhibit enormous variability in their genetic basis and phenotypic expression. The authors recommend that the diagnosis of TM or non-transfusion-dependent thalassemia (NTDT) should not be based on a one-time assessment.

Iron in Health and Disease: An Update.

Iron is an essential micronutrient for oxygen transport, cellular energy metabolism, and many enzymatic reactions. Complex physiological processes have evolved for iron acquisition to meet metabolic needs while avoiding toxicity from iron-generated free radicals. Systemic iron homeostasis is centered around the regulation of iron absorption from duodenum and iron release from stores by hepcidin.

Nutritional Deficiencies Are Common in Patients with Transfusion-Dependent Thalassemia and Associated with Iron Overload.

Patients with thalassemia are frequently deficient in key micronutrients. Attempts to correct these inadequacies through nutritional supplementation have been met with some success, although disparities between intake and circulating levels continue to be observed. This study employed a convenience sample of 41 well-nourished transfusion dependent patients with thalassemia to identify possible mechanisms behind nutritional deficiencies.

Transfusion practices and complications in thalassemia.

Background: The severe forms of thalassemia are the most common inherited anemias managed with regular blood transfusion therapy. Transfusion policies and complications are critical to quality of life and survival, but there is a lack of standardized care.

Study Design And Methods: A survey of 58 items was completed in 2016 by 11 centers in California, Washington, Oregon, Nevada, and Arizona providing long-term care for thalassemia.

A novel nutritional intervention improves lung function in overweight/obese adolescents with poorly controlled asthma: the Supplemental Nutrition in Asthma Control (SNAC) pilot study.

Asthma in the obese is often severe, difficult to treat, and characterized by less eosinophilic inflammation than asthma in the nonobese. Obesity-associated metabolic dysregulation may be a causal factor. We previously reported that a nutrient- and fiber-dense bar [Children's Hospital Oakland Research Institute (CHORI)-bar], which was designed to fill gaps in poor diets, improved metabolism in healthy overweight/obese (OW/OB) adults.

Epidemiologic and clinical characteristics of nontransfusion-dependent thalassemia in the United States.

Background: Nontransfusion-dependent thalassemia (NTDT) refers to a diverse group of thalassemia mutations and clinical phenotypes that do not require chronic transfusions. It is increasingly prevalent in the United States.

Procedure: This study reviews the epidemiology and clinical characteristics of 138 patients with NTDT treated at four US thalassemia centers from 1997 to 2014.

Favorable outcomes after in utero transfusion in fetuses with alpha thalassemia major: a case series and review of the literature.

Objective: Alpha thalassemia major (ATM) is often fatal in utero due to severe hydrops fetalis. Although in utero transfusions (IUTs) are increasingly used to allow fetal survival in ATM, prenatal and postnatal outcomes are not well described.

Methods: We retrospectively reviewed cases of ATM at our institution treated with consecutive IUT.