Real-world experience with iron chelation therapy in transfusion-dependent thalassemia: impact of the oral chelators' era.

Iron overload is a common complication in patients with transfusion-dependent-thalassemia that can lead to end-organ damage. Management of iron overload has considerably evolved since the early 2000s with the approval of oral iron chelators and widespread use of MRI monitoring. We conducted a retrospective cohort study of 144 patients with transfusion-dependent-thalassemia treated at a single center in the US and followed since initiation of regular transfusion therapy.

Anemia and iron overload as prognostic markers of outcomes in β-thalassemia.

Introduction: Ineffective erythropoiesis and subsequent anemia as well as primary and secondary (transfusional) iron overload are key drivers for morbidity and mortality outcomes in patients with β-thalassemia.

Areas Covered: In this review, we highlight evidence from observational studies evaluating the association between measures of anemia and iron overload versus outcomes in both non-transfusion-dependent and transfusion-dependent forms of β-thalassemia.

Expert Opinion: Several prognostic thresholds have been identified with implications for patient management.

Iron chelation therapy for children with transfusion-dependent β-thalassemia: How young is too young?

In this review, we provide a summary of evidence on iron overload in young children with transfusion-dependent β-thalassemia (TDT) and explore the ideal timing for intervention. Key data from clinical trials and observational studies of the three available iron chelators deferoxamine, deferiprone, and deferasirox are also evaluated for inclusion of subsets of young children, especially those less than 6 years of age. Evidence on the efficacy and safety of iron chelation therapy for children ≥2 years of age with transfusional iron overload is widely available.

Rates of severe neutropenia and infection risk in patients treated with deferiprone: 28 years of data.

Patients treated with deferiprone for transfusional iron overload may experience idiosyncratic drug-induced neutropenia (IDIN) that may increase risk of infection. This analysis examined the rates of severe IDIN and risk of serious infections at different absolute neutrophil count (ANC) levels during deferiprone treatment. Events of severe IDIN (ANC <0.

Αlpha-thalassemia: A practical overview.

α-Thalassemia is an inherited blood disorder characterized by decreased synthesis of α-globin chains that results in an imbalance of α and β globin and thus varying degrees of ineffective erythropoiesis, decreased red blood cell (RBC) survival, chronic hemolytic anemia, and subsequent comorbidities. Clinical presentation varies depending on the genotype, ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease. Management of patients with α-thalassemia is primarily supportive, addressing either symptoms (eg, RBC transfusions for anemia), complications of the disease, or its transfusion-dependence (eg, chelation therapy for iron overload).

Profile of Luspatercept in the Treatment of Anemia in Adults with Non-Transfusion-Dependent β-Thalassemia (NTDT): Design, Development and Potential Place in Therapy.

Over the past decade, evidence has been mounting on the detrimental clinical sequelae of untreated anemia in patients with non-transfusion-dependent β-thalassemia (NTDT). There are no pharmacologic agents that are specifically approved for the management of anemia in NTDT, and available options such as splenectomy, transfusion therapy, and hydroxyurea each come with their own shortcomings, especially for long-term use. Luspatercept is an erythroid maturation agent that has been evaluated in a Phase 2, randomized trial and showed a significant benefit in raising hemoglobin level by at least 1 g/dL in adults with NTDT and a baseline hemoglobin level ≤10 g/dL.

Management of luspatercept therapy in patients with transfusion-dependent β-thalassaemia.

Patients with transfusion-dependent β-thalassaemia require lifelong, regular red blood cell transfusions for survival; however, frequent blood transfusions are associated with an increased risk of iron overload, transfusion-transmitted disease and alloimmunization, as well as reduced quality of life. Luspatercept, an erythroid maturation agent that promotes late-stage erythroid maturation independently of erythropoietin, has demonstrated efficacy in reducing transfusion burden in patients with transfusion-dependent β-thalassaemia. In this review, we discuss treatment initiation, ongoing evaluation, dose adjustment and management of adverse events in transfusion-dependent patients with β-thalassaemia receiving luspatercept, and we provide guidance on how to determine whether patients are deriving clinical benefit.

Clinical Classification, Screening, and Diagnosis in Beta-Thalassemia and Hemoglobin E/Beta-Thalassemia.

This article reviews the classification of beta-thalassemia syndromes, correlating clinical severity and genotype in the earlier classification, and broadening it recently based on clinical severity and transfusion status. The classification is dynamic, and individuals may progress from transfusion-independent to transfusion-dependent. Early and accurate diagnosis prevents delays in instituting treatment and comprehensive care, and precludes inappropriate and potentially harmful interventions.

Thalassaemia-A global view.

The thalassaemias are a group of genetic disorders of haemoglobin which are endemic in the tropics but are now found worldwide due to migration. Basic standard of care therapy includes regular transfusions to maintain a haemoglobin level of around 10 g/dL, together with iron chelation therapy to prevent iron overload. Novel therapies, bone marrow transplantation, and gene therapy are treatment options that are unavailable in many countries with stressed economies.

Optimal strategies for carrier screening and prenatal diagnosis of α- and β-thalassemia.

The thalassemias are inherited quantitative disorders of hemoglobin synthesis with a significant worldwide burden, which result in a wide spectrum of disease from the most severe transfusion-dependent form to the mildest asymptomatic carrier state. In this article, we discuss the importance of carrier, prenatal, and newborn screening for thalassemia. We examine the rationale for who should be screened and when, as well as the current methodology for screening.

Health-related quality of life and fatigue in children and adults with pyruvate kinase deficiency.

Pyruvate kinase deficiency (PKD) is the most common cause of congenital nonspherocytic hemolytic anemia. Although recognition of the disease spectrum has recently expanded, data describing its impact on health-related quality of life (HRQoL) are limited. In this prospective international cohort of 254 patients (131 adults and 123 children) with PKD, we used validated measures to assess the impact of disease on HRQoL (EuroQol 5-Dimension Questionnaire, Pediatric Quality of Life Inventory Generic Core Scale version 4.

Pyruvate kinase deficiency in children.

Background: Pyruvate kinase deficiency (PKD) is a rare, autosomal recessive red blood cell enzyme disorder, which leads to lifelong hemolytic anemia and associated complications from the disease and its management.

Methods: An international, multicenter registry enrolled 124 individuals younger than 18 years old with molecularly confirmed PKD from 29 centers. Retrospective and prospective clinical data were collected.

Comorbidities and complications in adults with pyruvate kinase deficiency.

Objectives: Pyruvate kinase (PK) deficiency is caused by PKLR gene mutations, leading to defective red blood cell glycolysis and hemolytic anemia. Rates of comorbidities and complications by transfusion history and relative to the general population remain poorly quantified.

Methods: Data for patients aged ≥ 18 years with two confirmed PKLR mutations were obtained from the PK deficiency Natural History Study (NCT02053480).

An assessment of the continuing medical education needs of US physicians in the management of patients with beta thalassemia.

Patients with beta thalassemia are benefitting from longer life expectancies, highlighting the importance of appropriate transition from pediatric to adult care. Data are limited regarding continuity of care and adult hematologists' management of patients with beta thalassemia. We conducted a survey of practicing US hematologists to identify practice gaps, attitudes, and barriers to optimal patient management among US-practicing hematologists.

Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers.

Systematic Literature Review of the Burden of Disease and Treatment for Transfusion-dependent β-Thalassemia.

Purpose: β-Thalassemia is an inherited blood disorder characterized by reduced or no production of adult hemoglobin. Systematic identification of the burden of β-thalassemia with contemporary treatments is lacking in published literature. Thus, a gap exists in understanding the baseline burden on which to assess future treatments.

Bone Marrow Failure in Children: Approach to Diagnosis and Treatment.

Bone marrow failure has many different etiologies, including genetic defects which manifest with specific syndromes, as well as acquired conditions as a result of insults to the bone marrow leading to aplasia. The clinical picture is varied and clues for the underlying cause may or may not be evident at the time of presentation, frequently leading to a complex workup with a battery of tests often done to rule out genetic defects. The treatment approach for bone marrow failure is very dependent on the underlying cause, which makes it all the more critical to have an accurate diagnosis.