Update on the use of deferasirox in the management of iron overload

Regular blood transfusions as supportive care for patients with chronic anemia inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload cause significant morbidity and mortality if not effectively treated with chelation therapy. Based on a comprehensive clinical development program, the once-daily, oral iron chelator deferasirox (Exjade®) is approved for the treatment of transfusional iron overload in adult and pediatric patients with various transfusion-dependent anemias, including β-thalassemia and the myelodysplastic syndromes. Deferasirox dose should be titrated for each individual patient based on transfusional iron intake, current iron burden and whether the goal is to decrease or maintain body iron levels. Doses of >30 mg/kg/day have been shown to be effective with a safety profile consistent with that observed at doses <30 mg/kg/day. Recent data have highlighted the ability of deferasirox to decrease cardiac iron levels and to prevent the accumulation of iron in the heart. The long-term efficacy and safety of deferasirox for up to 5 years of treatment have now been established. The availability of this effective and generally well tolerated oral therapy represents a significant advance in the management of transfusional iron overload

TSH-Suppressive Therapy: A Thorny Issue

Thyroid stimulating hormone (TSH)-suppressive therapy with levothyroxine is a cornerstone of thyroid carcinoma follow-up therapy, but the achievement of therapeutic goals must be balanced against L-T4 side effects. We describe the case of a 64-year-old cardiopathic patient with papillary thyroid carcinoma and autoimmune thyroiditis, whose cardiac condition worsened during TSH-suppressive therapy. TSH concentrations also fluctuated widely because of changing intestinal absorption due to coeliac disease

Metastatic Spreading of Community Acquired Staphylococcus aureus Bacteraemia

A 29-year-old woman presented to the Fondazione IRCCS “Cà Granda” Ospedale Maggiore, a tertiary care university hospital in Milan (Italy), with skin lesions, fever, myalgia, joint pain and swelling, and a one-week history of low back pain. The diagnosis was Staphylococcus aureus (S. aureus) bacteraemia spreading to skin, bones, and joints and a lumbosacral epidural abscess L5-S2. Neither initial focus nor predisposing conditions were apparent. The antibiotic therapy was prolonged for six-weeks with the resolution of fever, skin lesions, articular inflammation, and the epidural abscess. Community-acquired S. aureus infections can affect patients without traditional healthcare-associated risk factors, and community acquisition is a risk-factor for the development of complications. Raised awareness of S. aureus bacteraemia, also in patients without healthcare-associated risk factors, is important in the diagnosis, management, and control of this infection, because failure to recognise patients with serious infection and lack of understanding of empirical antimicrobial selection are associated with a high mortality rate in otherwise healthy people

2021 update on clinical trials in β‐thalassemia

AbstractThe treatment landscape for patients with β‐thalassemia is witnessing a swift evolution, yet several unmet needs continue to persist. Patients with transfusion‐dependent β‐thalassemia (TDT) primarily rely on regular transfusion and iron chelation therapy, which can be associated with considerable treatment burden and cost. Patients with non‐transfusion‐dependent β‐thalassemia (NTDT) are also at risk of significant morbidity due to the underlying anemia and iron overload, but treatment options in this patient subgroup are limited. In this review, we provide updates on clinical trials of novel therapies targeting the underlying pathology in β‐thalassemia, including the α/non‐α‐globin chain imbalance, ineffective erythropoiesis, and iron dysregulation

Emerging drugs in randomized controlled trials for sickle cell disease: are we on the brink of a new era in research and treatment?

ABSTRACT Introduction: Sickle cell disease (SCD) is caused by a mutation in the HBB gene which is key for making a component of hemoglobin. The mutation leads to the formation of an abnormal hemoglobin molecule called sickle hemoglobin (HbS). SCD is a chronic, complex disease with a multiplicity of pathophysiological targets; it has high morbidity and mortality. Hydroxyurea has for many years been the only approved drug for SCD; hence, the development of new therapeutics is critical. Areas covered: This article offers an overview of the key studies of new therapeutic options for SCD. We searched the PubMed database and Cochrane Database of Systemic Reviews for agents in early phase clinic trials and preclinical development. Expert opinion: Although knowledge of SCD has progressed, patient survival and quality of life must be improved. Phase II and phase III clinical trials investigating pathophysiology-based novel agents show promising results in the clinical management of SCD acute events. The design of longterm clinical studies is necessary to fully understand the clinical impact of these new therapeutics on the natural history of the disease. Furthermore, the building of global collaborations will enhance the clinical management of SCD and the design of primary outcomes of future clinical trials

2021 Thalassaemia International Federation Guidelines for the Management of Transfusion-dependent Thalassemia

Beta-thalassemia and particularly its transfusion-dependent form (TDT) is a demanding clinical condition, requiring life-long care and follow-up, ideally in specialized centers and by multidisciplinary teams of experts. Despite the significant progress in TDT diagnosis and treatment over the past decades that has dramatically improved patients' prognosis, its management remains challenging. On one hand, diagnostic and therapeutic advances are not equally applied to all patients across the world, particularly in several high-prevalence eastern regions. On the other, healthcare systems in low-prevalence western countries that have recently received large numbers of migrant thalassemia patients, were not ready to address patients' special needs. Thalassaemia International Federation (TIF), a global patient-driven umbrella federation with 232 member-associations in 62 countries, strives for equal access to quality care for all patients suffering from thalassemia or other hemoglobinopathies in every part of the world by promoting education, research, awareness, and advocacy. One of TIF's main actions is the development and dissemination of clinical practice guidelines for the management of these patients. In 2021, the fourth edition of TIF's guidelines for the management of TDT was published. The full text provides detailed information on the management of TDT patients and the clinical presentation, pathophysiology, diagnostic approach, and treatment of disease complications or other clinical entities that may occur in these patients, while also covering relevant psychosocial and organizational issues. The present document is a summary of the 2021 TIF guidelines for TDT that focuses mainly on clinical practice issues and recommendations

Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective

A significant amount of attention has recently been devoted to the mechanisms involved in hemoglobin (Hb) switching, as it has previously been established that the induction of fetal hemoglobin (HbF) production in significant amounts can reduce the severity of the clinical course in diseases such as beta-thalassemia and sickle cell disease (SCD). While the induction of HbF using lentiviral and genome-editing strategies has been made possible, they present limitations. Meanwhile, progress in the use of pharmacologic agents for HbF induction and the identification of novel HbF-inducing strategies has been made possible as a result of a better understanding of gamma-globin regulation. In this review, we will provide an update on all current pharmacological inducer agents of HbF in beta-thalassemia and SCD in addition to the ongoing research into other novel, and potentially therapeutic, HbF-inducing agents

Hepatocellular carcinoma in hepatitis-negative patients with thalassemia intermedia: a closer look at the role of siderosis

Abstract Patients with thalassemia are often exposed to several risk factors for developing hepatocellular carcinoma (HCC) due to their repeated transfusions. However, even transfusion-independent patients with thalassemia intermedia (TI) can develop HCC, which is mainly attributed to a state of iron overload. We report here two cases and review the literature for the association between TI and HCC. Along with our cases, a total of 36 cases of HCC in thalassemic patients were reported in the literature. Of these, 22 (61%) were TI patients with 6 (27%) of them being hepatitis B and C negative. There was no consistency in their characteristics; therefore, we recommended screening thresholds for HCC in TI patients based on their total liver iron concentration (LIC)

Pregnancy outcome in patients with β-thalassemia intermedia at two tertiary care centers, in Beirut and Milan

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