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Patients with transfusion-dependent β-thalassemia were randomly assigned to receive luspatercept (a binder for TGF-β family member ligands) or placebo. During any 12-week period, a greater percentage of patients in the luspatercept group than in the placebo group had a reduction of at least 33% (70.5% vs. 29.5%) or at least 50% (40.2% vs. 6.3%) in the transfusion requirement.

A year-long, phase 3, randomized trial involving patients with sickle cell disease showed that the median number of pain crises was 25% lower and the median number of hospitalizations was 33% lower with l -glutamine supplementation than with placebo.

Non-transfusion-dependent (NTD) thalassaemia is characterised by ineffective erythropoiesis and haemolytic anaemia, leading to long-term complications, poor quality of life, and early mortality. No oral disease-modifying therapies are approved for β-thalassaemia and no agents are approved for α-thalassaemia. The objective of this study was to evaluate the efficacy and safety of mitapivat, an oral activator of pyruvate kinase, in adults with NTD α-thalassaemia or NTD β-thalassaemia. ENERGIZE is a phase 3, double-blind, randomised, placebo-controlled trial followed by an open-label extension conducted at 70 hospitals in 18 countries globally. Participants had to be aged 18 years or older with NTD α-thalassaemia or NTD β-thalassaemia and haemoglobin concentrations of 10 g/dL or lower. Participants were randomly assigned 2:1 to mitapivat or placebo (100 mg orally twice a day for 24 weeks) via a central interactive response technology system using block randomisation, stratified by baseline haemoglobin concentration and thalassaemia genotype. Everyone was masked to the patients' treatment assignment until the study was unblinded for the analysis of the primary endpoint. The primary endpoint was haemoglobin response (≥1·0 g/dL increase from baseline in mean haemoglobin concentration from week 12 through week 24), analysed in all patients who were randomly assigned. Safety was analysed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT04770753, and is active but not recruiting. Between Nov 8, 2021, and March 31, 2023, 235 patients were screened, of whom 194 were enrolled (123 [63%] were female and 71 [37%] were male). 130 patients were randomly assigned to mitapivat and 64 patients to placebo and formed the full analysis set. One patient in each group was randomly assigned but not given treatment and was therefore excluded from the safety analysis set (mitapivat 129 patients and placebo 63 patients). Seven patients in the mitapivat group and one patient in the placebo group discontinued treatment before the end of the 24-week double-blind period. 55 (42%) of 130 patients in the mitapivat group had a haemoglobin response versus one (2%) of 64 in the placebo group (least-squares mean difference 41% [95% CI 32–50], two-sided p<0·0001). Adverse events were reported in 107 (83%) of 129 patients who received mitapivat and 50 (79%) of 63 patients who received placebo. The most commonly reported adverse events with mitapivat were headache (29 [22%] of 129 patients in the mitapivat group vs six [10%] of 63 in the placebo group), initial insomnia (18 [14%] vs three [5%]), nausea (15 [12%] vs five [8%]), and upper respiratory tract infection (14 [11%] vs four [6%]). No deaths were reported. Mitapivat could be a new oral treatment for adults with NTD α-thalassaemia or NTD β-thalassaemia by increasing haemoglobin concentration and improving fatigue. Agios Pharmaceuticals.

Hydroxyurea is an antimetabolite drug that induces fetal haemoglobin in sickle cell disease. However, its clinical usefulness in β-thalassaemia is unproven. We conducted a randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of hydroxyurea in transfusion-dependent β-thalassaemia. Sixty patients were assigned 1:1 to oral hydroxyurea 10–20 mg/kg/day or placebo for 6 months by stratified block randomisation. Hydroxyurea treatment did not alter the blood transfusion volume overall. However, a significantly higher proportion of patients on hydroxyurea showed increases in fetal haemoglobin percentage (89% vs. 59%; p  < 0.05) and reductions in erythropoietic stress as measured by soluble transferrin receptor concentration (79% vs. 40%; p  < 0.05). Based on fetal haemoglobin induction (> 1.5%), 44% of patients were identified as hydroxyurea-responders. Hydroxyurea-responders, required significantly lower blood volume (77 ± SD27ml/kg) compared to hydroxyurea-non-responders (108 ± SD24ml/kg; p  < 0.01) and placebo-receivers (102 ± 28ml/kg; p  < 0.05). Response to hydroxyurea was significantly higher in patients with HbE β-thalassaemia genotype (50% vs. 0%; p  < 0.01) and Xmn1 polymorphism of the γ-globin gene (67% vs. 27%; p  < 0.05). We conclude that oral hydroxyurea increased fetal haemoglobin percentage and reduced erythropoietic stress of ineffective erythropoiesis in patients with transfusion-dependent β-thalassaemia. Hydroxyurea reduced the transfusion burden in approximately 40% of patients. Response to hydroxyurea was higher in patients with HbE β-thalassaemia genotype and Xmn 1 polymorphism of the γ-globin gene.

Curcuminoids, polyphenol compounds in turmeric, possess several pharmacological properties including antioxidant, iron-chelating, and anti-inflammatory activities. Effects of curcuminoids in thalassemia patients have been explored in a limited number of studies using different doses of curcuminoids. The present study aims to evaluate the effects of 24-week curcuminoids supplementation at the dosage of 500 and 1000 mg/day on iron overload, oxidative stress, hypercoagulability, and inflammation in non-transfused β-thalassemia/Hb E patients. In general, both curcuminoids dosages significantly lowered the levels of oxidative stress, hypercoagulability, and inflammatory markers in the patients. In contrast, reductions in iron parameter levels were more remarkable in the 1000 mg/day group. Subgroup analysis revealed that a marker of hypercoagulability was significantly decreased only in patients with baseline ferritin ≤ 1000 ng/ml independently of curcuminoids dosage. Moreover, the alleviation of iron loading parameters was more remarkable in patients with baseline ferritin > 1000 ng/ml who receive 1000 mg/day curcuminoids. On the other hand, the responses of oxidative stress markers were higher with 500 mg/day curcuminoids regardless of baseline ferritin levels. Our study suggests that baseline ferritin levels should be considered in the supplementation of curcuminoids and the appropriate curcuminoids dosage might differ according to the required therapeutic effect. Thai Clinical Trials Registry (TCTR): TCTR20200731003; July 31, 2020 “retrospectively registered”

•This study was a post hoc analysis of a randomized controlled trial with 100 patients with β-thalassemia major.•Thalidomide can improve the lifespan and reduce hemolysis of red blood cells in patients with β-thalassemia major.•Provide a new treatment alternative for improving the quality of life of patients with β-thalassemia major. Recent studies have shown the thalidomide's therapeutic potential in treatment of patients with β-thalassemia major. However, the effect of thalidomide on metabolism and lifespan of red blood cells (RBCs) is rarely reported. This study was a post hoc analysis of a randomized controlled trial (Chinese Clinical Trial Registry, ChiCTR1800015702). One hundred patients with β-thalassemia major were randomly assigned 1:1 to treatment with a placebo or thalidomide. The primary outcomes were the differences in RBC lifespan, reticulocyte count, and peripheral nucleated RBC count of patients after treatment of 12 weeks. Other indicators of hemolytic reaction were also analyzed. Compared with the placebo group after treatment of 12 weeks, the thalidomide group showed a longer RBC lifespan (16.29 ± 6.42 vs 12.90 ± 4.98 days; P = 0.004), smaller mean corpuscular volume (68.34 ± 7.79 vs 78.01 ± 6.33 fl; P < 0.001), smaller mean corpuscular hemoglobin (21.62 ± 2.85 vs 24.68 ± 2.69 pg; P < 0.001), and lower lactate dehydrogenase (190.00 [148.00 - 305.00] vs 251.00 [199.20 - 327.80]; P = 0.014). Meanwhile, thalidomide significantly increased the RBC lifespan at 24 weeks (21.24 ± 8.30 days; P < 0.001) and 48 weeks (23.21 ± 8.42 days; P < 0.001) when compared with baseline (12.8 ± 6.0 days). Thalidomide increases the RBC lifespan and reduces hemolytic reactions in patients with β-thalassemia major. Chinese Clinical Trial Registry identifier: ChiCTR1800015702.

•42 patients received a 500 mg/day quercetin and 42 others took a 500 mg/day placebo for 12 w.•Quercetin could significantly reduce ferritin and other serum iron factors (P > 0.05).•Quercetin significantly reduced hs-CRP (P = 0.046), but not TNF-α (p = 0.310).•According to our results, quercetin may be useful to reduce ferritin and inflammation in thalassemia major patients. The aim of this study was to determine whether quercetin can reduce iron overload and inflammation in thalassemic patients. Eighty four patients were recruited to this study and randomly assigned to two groups: 42 patients received a 500 mg/day quercetin tablet and 42 others took a 500 mg/day starch placebo for 12 weeks. Demographic, anthropometric and biochemical evaluation were performed. ANCOVA analysis revealed that compared to the control group, quercetin could reduce high sensitivity C-reactive protein (hs-CRP) (P = 0.046), iron (p = 0.036), ferritin (p = 0.043), and transferrin saturation (TS) (p = 0.008) and increase transferrin (p = 0.045) significantly, but it had no significant effect on total iron binding capacity (TIBC) (p = 0.734) and tumor necrosis factor α (TNF-α) (p = 0.310). Quercetin could ameliorate the iron status in thalassemia major, but its effect on inflammation is indistinctive.

IntroductionDespite the improvement in medical management, many patients with transfusion-dependent β-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent β-thalassaemia with very high iron overload.Methods and analysisThis is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent β-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6 months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6 months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures.Ethics and disseminationEthical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P/06/02/2023). The trial results will be disseminated in scientific publications in reputed journals.Trial registration numberThe trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR/2023/010).

Oxidative stress is a major mechanism contributing to the progression of β-thalassemia. To assess the effect of vitamin E and N-acetyl cysteine (NAC) as antioxidant agents on total oxidative stress (TOS) status and total antioxidant capacity (TAC) in patients with transfusion-dependent β-thalassemia (TDT). In this open-label randomized controlled trial, from May to August 2019, 78 eligible patients with TDT over the age of 18 were enrolled. All patients were registered at the Thalassemia Clinic of Shiraz University of Medical Sciences in Southern Iran. Patients were randomly allocated to the NAC group (10 mg/kg/day, orally), vitamin E group (10 U/kg/day, orally), and control group. The duration of the study was 3 months. The mean age of the participants was 28.5 ± 5.1 (range: 18–41) years. At the end of the study, TOS significantly decreased only in the vitamin E group (mean difference (MD), 95% confidence interval (CI): 0.27 (0.03–0.50), P = 0.026). TAC significantly decreased in both supplemented groups at the 3rd month of treatment (NAC group: MD (95% CI): 0.11 (0.04–0.18), P = 0.002 and vitamin E group: 0.09 (0.01–0.16), P = 0.022 respectively). Hemoglobin did not significantly change at the end of the study in each group (P > 0.05). Mild transient adverse events occurred in 4 patients of the NAC group and 5 patients of the vitamin E group with no need to discontinue the treatment. Vitamin E can be a safe and effective supplement in improving oxidative stress in patients with TDT. Moreover, it seems that a longer duration of using antioxidant supplements needs to make clinical hematologic improvement in TDT patients.

Background Iron overload‐induced oxidative stress and transfusion‐acquired hepatitis C virus (HCV) infection are the main reasons of liver damage in beta thalassemia major (β‐TM). Objectives Based on metformin’s hepatic benefits in nondiabetic populations, the study aims to investigate the safety and the potential hepatoprotective effect of metformin in HCV‐infected β‐TM adolescent patients. Methods This was a prospective, randomised, parallel, controlled, open‐label study in which 60 HCV‐infected β‐TM adolescent patients aged 11 to 18 years and receiving no antiviral therapy were selected and randomly assigned to treatment or control group in 1:1 allocation. Both groups were receiving β‐TM standard‐of‐care regimen, whereas metformin (500 mg, twice daily) was added to the treatment group's regimen only. Patients were prospectively followed up for 6 months with assessment of liver biochemical profile, oxidative stress markers, liver fibrosis, clinical symptom improvement and metformin's adverse effects. Results Aspartate aminotransferase serum level decreased significantly over time in the treatment group only (P = .013). However, improvement was not clinically significant and did not attain normality. Change in total antioxidant capacity and malondialdehyde serum levels indicated significantly improved oxidative stress status in the treatment group versus significant deterioration in the control group (P < .001). Fibrosis grade improvement was observed in 14 patients in the treatment group versus one improved case in the control group. Conclusion The use of metformin in HCV‐infected β‐TM adolescent patients as an adjuvant antioxidant hepatoprotective agent is promising and can improve liver damage.