Beta-thalassemia Intermedia Research Articles

Orphan designation: Autologous CD34+ haematopoietic stem cells transduced with lentiviral vector encoding the human betaA-T87Q-globin gene, Treatment of beta thalassaemia intermedia and major

Orphan designation: Autologous CD34+ haematopoietic stem cells transduced with lentiviral vector encoding the human betaA-T87Q-globin gene, Treatment of beta thalassaemia intermedia and major

PB2399 BETA THALASSEMIA MINOR PATIENTS: NOT TIRED, BUT DEPRESSED AND ANXIOUS

Background:The quality of life has been influenced unfavourably and the prevalance of either depression or anxiety has been increased in beta thalassemia major (BTM) and beta thalassemia intermedia (BTI) patients. Yet, the studies including the quality of life in beta thalassemia minor (BTm) subjects are limited and just the depression was demonstrated to be frequent in individuals with BTm, compared to the healthy population. Likewise, the data regarding the presence of fatique and anxiety in adult BTm subjects is insufficientAims:We aimed to investigate whether the severity of fatigue and the incidences of depression and anxiety of patients with BTm are different than healthy individuals using Fatigue Severity Scale (FSS) and Hospital Anxiety and Depression Scale (HADS).Methods:Seventy‐seven BTm subjects were included in this study. The individuals (n = 38) using any medications, alcohol or tobacco; and having any chronic diseases and sleeping disturbances, were excluded. The remaining 39 BTm subjects were enrolled in the study. They had also normal biochemical parameters, thyroid function tests and C‐reactive protein (CRP). Twenty‐five healthy control subjects who were matched with age, sex, marital status, educational status and body mass index (BMI), were also included.Results:The BTm and the control groups were comparable in terms of gender, age, BMI, educational status and marital status (p = 0.368, 0.755, 0.851, 0.785, 0.709 respectively) (Table 1). Fatigue Severity Scale score was ≥4 in 23 (59.0%) BTm subjects and in 15 (60%) control subjects (p = 1.0). HADS anxiety score was ≥10 in 20 (51.3%) BTm subjects and in 5 (20.0%) control subjects (p = 0.018) and HADS depression score was ≥ 7 in 20 (51.3%) BTm subjects and 6 (24.0%) healthy control subjects (p = 0.039). There was no correlation of hemoglobin with FSS score (p = 0.526, r = ‐0.105), HADS anxiety score (p = 0.703, r = ‐0.063) or HADS depression score (p = 0.718, r = ‐0.06) in BTm group (Table 2).Summary/Conclusion:We found that both depression and anxiety were higher in BTm patients than healthy individuals, but this difference was not feasible for fatigue.imageimage

Orphan designation: Autologous CD34+ cells transduced with lentiviral vector encoding the human beta globin gene, Treatment of beta thalassaemia intermedia and major

Orphan designation: Autologous CD34+ cells transduced with lentiviral vector encoding the human beta globin gene, Treatment of beta thalassaemia intermedia and major

Orphan designation: Synthetic double-stranded siRNA oligonucleotide directed against TMPRSS6 mRNA and covalently linked to a ligand containing three N-acetylgalactosamine residues, Treatment of beta-thalassaemia intermedia and major

Orphan designation: Synthetic double-stranded siRNA oligonucleotide directed against TMPRSS6 mRNA and covalently linked to a ligand containing three N-acetylgalactosamine residues, Treatment of beta-thalassaemia intermedia and major

Orphan designation: Synthetic double-stranded siRNA oligonucleotide directed against TMPRSS6 mRNA and covalently linked to a ligand containing three N-acetylgalactosamine residues, Treatment of beta-thalassaemia intermedia and major

Orphan designation: Synthetic double-stranded siRNA oligonucleotide directed against TMPRSS6 mRNA and covalently linked to a ligand containing three N-acetylgalactosamine residues, Treatment of beta-thalassaemia intermedia and major

Orphan designation: Autologous CD34+ haematopoietic stem cells transduced with lentiviral vector encoding the human betaA-T87Q-globin gene, Treatment of beta thalassaemia intermedia and major

Orphan designation: Autologous CD34+ haematopoietic stem cells transduced with lentiviral vector encoding the human betaA-T87Q-globin gene, Treatment of beta thalassaemia intermedia and major

Orphan designation: human apotransferrin, Treatment of beta-thalassaemia intermedia and major

Orphan designation: human apotransferrin, Treatment of beta-thalassaemia intermedia and major

Orphan designation: human apotransferrin, Treatment of beta-thalassaemia intermedia and major

Orphan designation: human apotransferrin, Treatment of beta-thalassaemia intermedia and major

Hb Knossos (HBB: c.82G\u2009>\u2009T), \u03b2-globin CD 5 (\u2212CT) (HBB: c.17_18delCT) and \u03b4-globin CD 59 (\u2212a) (HBD: c.179delA) mutations in a Syrian patient with \u03b2-thalassemia intermedia

BackgroundBeta thalassemia (β-thal) is an inherited hemoglobin disorder characterized by reduced synthesis of the hemoglobin that results in microcytic hypochromic anemia. β-Thalassemia intermedia (TI) is a clinical term of intermediate gravity between the carrier state and β-thalassemia major (β -TM).Case presentationWe describe a 12-year-old male proband originating from Al-Quneitra province - southwest Syria. Hematological investigations revealed, pallor and anemia (Hb 9 g/dl). The mean cell volume (MCV) 64 fL; mean cell hemoglobin (MCH) 21.8 pg. Capillary electrophoresis (CE) electropherogram revealed low level of Hb A1 (36.2%), high level of Hb F (62.2%) and low level of Hb A2 (1.6%). The proband requires blood transfusion occasionally. Direct DNA sequencing and Polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) for mutations detection were used. The molecular analysis revealed the presence of rare β+ Hb Knossos codon 27 (G > T) (HBB: c.82G > T) variant associated with β0 codon 5 [−CT] (HBB: c.17_18delCT) mutation in beta-globin (β-globin) gene and δ0 codon 59 [−A] (HBD: c.179delA) mutation in delta-globin (δ-globin) gene. The proband tested negative for the common deletional forms of alpha thalassemia (α-thal). Polymorphism of the Xmn-I locus (HBG2: c.-211C > T) revealed that the proband had a homozygous [TT] for Xmn-1 locus.ConclusionsTo our knowledge, this is the first report of beta thalassemia intermedia due to combination of Hb Knossos /codon 5 [−CT] associated with δ0 codon 59 [−A] in Syrian patient. On the other hand, in Syria, β-thal carriers who have low level of Hb A2 due to decreased δ-chain production, different δ-thal gene mutations must be screened to avoid the failure diagnosis of β-thal disease.

Multiple Alloantibodies Induced Autoimmune Hemolytic Anemia in Beta Thalassemia Woman with Megaloblastic Anemia during Pregnancy: A Case Report and Literature Review

Thalassemia is prevalent in Southern China and pregnancy with thalassemia becomes not rare in this area. Due to the unique pathophysiologic mechanism, pregnant complications in beta thalassemia are more complicated than normal pregnancy, such as hypercoagulation state, infant intrauterine growth restriction, impaired heart function and anemia. Despite of these, the clinical outcome of beta thalassemia pregnancy has been reported better currently. In this article, we report one interesting and distinct case of beta thalassemia pregnancy with complicated anemia. A pregnant woman, with beta thalassemia intermedia and underlying megaloblastic anemia, suffers the complex autoimmune hemolytic anemia after delivery. Screening for antibodies identifies two alloantibodies, anti-E IgG and anti-Lea IgM antibodies, which both contribute to the autoimmune hemolytic anemia. Glucocorticoid combined with immunoglobin has a good response and warm blood transfusion is also important in the treatment.

Assessment of Iron Overload and Role of Genetic Modifiers in Patients with Beta Thalassemia Intermedia

Assessment of Iron Overload and Role of Genetic Modifiers in Patients with Beta Thalassemia Intermedia

Orphan designation: 1-(3-methylbutanoyl)-L-aspartyl-L-threonyl-L-histidyl-L-phenylalanyl-L-prolyl-(L-cystinyl-L-isoleucyl-[(N6-(S)-4-carboxy-4-palmitamidobutanoyl)-L-lysinyl]-L-phenylalanyl-L-glutamyl-L-prolyl-L-arginyl-L-serinyl-L-lysinyl-L-glycinyl-L-cystinyl)-L-lysinamide, disulfide, acetate salt, Treatment of beta-thalassaemia intermedia and major

Orphan designation: 1-(3-methylbutanoyl)-L-aspartyl-L-threonyl-L-histidyl-L-phenylalanyl-L-prolyl-(L-cystinyl-L-isoleucyl-[(N6-(S)-4-carboxy-4-palmitamidobutanoyl)-L-lysinyl]-L-phenylalanyl-L-glutamyl-L-prolyl-L-arginyl-L-serinyl-L-lysinyl-L-glycinyl-L-cystinyl)-L-lysinamide, disulfide, acetate salt, Treatment of beta-thalassaemia intermedia and major

Orphan designation: 1-(3-methylbutanoyl)-L-aspartyl-L-threonyl-L-histidyl-L-phenylalanyl-L-prolyl-(L-cystinyl-L-isoleucyl-[(N6-(S)-4-carboxy-4-palmitamidobutanoyl)-L-lysinyl]-L-phenylalanyl-L-glutamyl-L-prolyl-L-arginyl-L-serinyl-L-lysinyl-L-glycinyl-L-cystinyl)-L-lysinamide, disulfide, acetate salt, Treatment of beta-thalassaemia intermedia and major

Orphan designation: 1-(3-methylbutanoyl)-L-aspartyl-L-threonyl-L-histidyl-L-phenylalanyl-L-prolyl-(L-cystinyl-L-isoleucyl-[(N6-(S)-4-carboxy-4-palmitamidobutanoyl)-L-lysinyl]-L-phenylalanyl-L-glutamyl-L-prolyl-L-arginyl-L-serinyl-L-lysinyl-L-glycinyl-L-cystinyl)-L-lysinamide, disulfide, acetate salt, Treatment of beta-thalassaemia intermedia and major

Global analysis of erythroid cells redox status reveals the involvement of Prdx1 and Prdx2 in the severity of beta thalassemia.

β-thalassemia is a worldwide distributed monogenic red cell disorder, characterized by an absent or reduced beta globin chain synthesis. The unbalance of alpha-gamma chain and the presence of pathological free iron promote severe oxidative damage, playing crucial a role in erythrocyte hemolysis, exacerbating ineffective erythropoiesis and decreasing the lifespan of red blood cells (RBC). Catalase, glutathione peroxidase and peroxiredoxins act together to protect RBCs from hydrogen peroxide insult. Among them, peroxiredoxins stand out for their overall abundance and reactivity. In RBCs, Prdx2 is the third most abundant protein, although Prdxs 1 and 6 isoforms are also found in lower amounts. Despite the importance of these enzymes, Prdx1 and Prdx2 may have their peroxidase activity inactivated by hyperoxidation at high hydroperoxide concentrations, which also promotes the molecular chaperone activity of these proteins. Some studies have demonstrated the importance of Prdx1 and Prdx2 for the development and maintenance of erythrocytes in hemolytic anemia. Now, we performed a global analysis comparatively evaluating the expression profile of several antioxidant enzymes and their physiological reducing agents in patients with beta thalassemia intermedia (BTI) and healthy individuals. Furthermore, increased levels of ROS were observed not only in RBC, but also in neutrophils and mononuclear cells of BTI patients. The level of transcripts and the protein content of Prx1 were increased in reticulocyte and RBCs of BTI patients and the protein content was also found to be higher when compared to beta thalassemia major (BTM), suggesting that this peroxidase could cooperate with Prx2 in the removal of H2O2. Furthermore, Prdx2 production is highly increased in RBCs of BTM patients that present high amounts of hyperoxidized species. A significant increase in the content of Trx1, Srx1 and Sod1 in RBCs of BTI patients suggested protective roles for these enzymes in BTI patients. Finally, the upregulation of Nrf2 and Keap1 transcription factors found in BTI patients may be involved in the regulation of the antioxidant enzymes analyzed in this work.

Evaluation of Endocrine Complications in Beta-Thalassemia Intermedia Patients: A Cross Sectional Multi-Center Study

The diagnosis of beta thalassemia intermedia (BTI) is mainly based on the severity of clinical phenotype. It is associated with a wide range of specific complications including extramedullary hematopoiesis, leg ulcers, gallstones, hypercoagulable state, pulmonary hypertension (PHT), endocrine disorders and osteoporosis. The commonest endocrine complication in beta thalassemia major (TM) patients is hypogonadism followed by hypothyroidism and diabetes but the data on endocrine disorders in BTI patients are scarce. The aim of this study is to determine the prevalence of endocrine complications in a large series of BTI patients.Methods: In this multi-countries cross-sectional study, all BTI patients registered at 12 thalassemic treatment centers in Iran (2 Centers), Italy (2 Centers), Greece, Turkey (2 centers), Oman, Qatar, Jordan, Cyprus and United Kingdom were enrolled during 2017. Non transfusion- dependent beta-thalassemia patients or those who received blood transfusion 3-4 times or less annually, were evaluated. Required information was collected from medical records using a designed questionnaire. Demographic data, clinical characteristics and laboratory data included age, sex, splenectomy, type of treatment (blood transfusion, iron chelation, hydroxyurea), hormonal assays, bone mineral density, calcium -phosphorous metabolism, serum ferritin, liver function tests, fetal and total hemoglobin levels, platelet and nucleated red blood cell counts, were collected.Results: A total of 721 BTI patients were enrolled in the survey from 9 countries. The most prevalent disease-related complications were osteoporosis (21.6%) and hypogonadism (12.6%) followed by: central hypothyroidism (8.3%), non-insulin-dependent diabetes mellitus (7.8%), primary hypothyroidism (5.5%), insulin-dependent diabetes mellitus (4.2%), hypoparathyroidism (2.2%), growth hormone deficiency (1.1%), adrenal mass (1%) and thyroid cancer (0.5%).Conclusion: This study evaluated the largest cohort of BTI patients with endocrine disorders. Although BTI patients are non-transfusion dependent or only occasionally transfused, iron-overload due to increased intestinal iron absorption and enhanced bone marrow activity cause endocrine disorders and osteoporosis. This study demonstrate that although endocrine complications are less common in patients with BTI compared to data reported in literature in TM patients , a regular monitoring with timely diagnosis and proper management underscoring on osteoporosis and gonadal disorders are crucial to prevent endocrine complications in these patients. DisclosuresNo relevant conflicts of interest to declare.

Orphan designation: Bitopertin, Treatment of beta-thalassaemia intermedia and major

Orphan designation: Bitopertin, Treatment of beta-thalassaemia intermedia and major

The survival rate of patients with beta-thalassemia major and intermedia and its trends in recent years in Iran.

OBJECTIVESThalassemia is a common genetic disease in Iran, especially in the north and south of Iran. The present study sought to determine the survival rate of patients with thalassemia in highly endemic regions of Iran and its variation in patients born before and after 1971.METHODSThe present historical cohort study extracted data from the health records of patients with beta-thalassemia major, beta-thalassemia intermedia, and sickle beta-thalassemia who had presented to thalassemia treatment centers in the past years. The collected data were analyzed using the Kaplan-Meier test, the log-rank test, and the chi-square test.RESULTSOf the total of 5,491 medical records (2,647 men and 2,634 women; mean age, 23.81±11.32 years), 3,936 belonged to patients with beta-thalassemia major, and 999 and 89 to patients with beta-thalassemia intermedia and sickle beta-thalassemia, respectively. In 467 cases, the type of thalassemia was not clear. The cumulative survival rate was calculated as 0.92, 0.83, 0.74, and 0.51 by ages 25, 35, 45, and 55, respectively. The hazard ratio of death was 4.22 (p<0.05) for beta-thalassemia major and 0.77 for beta-thalassemia intermedia (p=0.70). It was calculated as 1.45 for men patients and as 3.82 for single patients.CONCLUSIONSThe present study showed relatively high survival rates in patients with thalassemia. The survival of patients was unfavorable in poorer regions (Zahedan and Iranshahr). Factors including women gender, a higher level of education, being married, and living in metropolises decreased the risk of death at younger ages and improved survival.

PSY177 - HEALTH-RELATED QUALITY OF LIFE OF PATIENTS WITH BETA-THALASSEMIA

Beta-thalassemias are a group of genetic hemoglobinopathies. Those with beta-thalassemia minor typically do not require clinical interventions for anemia whereas beta-thalassemia intermedia or major patients require intermittent or chronic blood transfusions with iron-chelation therapies, respectively. This study aimed to review the humanistic burden of beta-thalassemia on patients and caregivers. Systematic searches were conducted in MEDLINE, EMBASE and Cochrane CENTRAL to identify relevant studies published in English in the past 10 years. No geographic restrictions were applied and all studies with population size N≥100 were considered. 133 publications (of 911 references identified) were selected for full-text screening. This resulted in 25 included full-text publications which evaluated the humanistic burden of beta-thalassemia, as measured by generic health-related quality of life (QoL) instruments such as SF-36, WHOQoL, EQ5D and PedsQL. The majority of studies (n=14) were conducted in beta-thalassemia major only, while eleven studies included patients with beta-thalassemia intermedia or other types of thalassemia. Almost half of the studies (n=12) were conducted in Iran and the remaining studies sampled populations from various geographic areas including North America, Europe, Australia, and Asia. The QoL was negatively impacted in both pediatric and adult patients, compared to age- and sex-matched healthy controls. Conflicting QoL findings emerged in patients who were transfusion-dependent compared to those who were not transfusion-dependent. Between patients requiring iron-chelation, QoL was better in those receiving oral chelation compared to those receiving injectable chelation. Based on the available data, beta-thalassemia has a negative impact on the QoL of affected individuals, and use of oral chelation therapies may be associated with a better QoL relative to injectable chelation therapies.

Efficacy and safety of resveratrol, an oral hemoglobin F-augmenting agent, in patients with beta-thalassemia intermedia.

Recently, resveratrol showed induction of γ-globin mRNA synthesis in human erythroid precursors and reducing oxidative stress in red cells of thalassemia patients in many in vitro studies. We aimed to investigate the efficacy and safety of resveratrol, for the first time, in non-transfusion-dependent beta-thalassemia intermedia (B-TI) in Southern Iran. In this double-blind randomized clinical trial, 54 patients with B-TI were investigated during 6months between October 2016 and March 2017. Patients were randomly allocated into three groups by simple randomization method. Group 1 (hydroxyurea (HU) and placebo, 18 patients), group 2 (resveratrol/piperine and placebo, 16 patients), and group 3(HU and resveratrol/piperine, 20 patients). Primary end point was considered as change in hemoglobin (Hb) levels and need for blood transfusion. Drug safety was considered as a secondary end point. Mean age of the patients was 28.2 ± 5.6 (18-42) years. Response rate was not significantly different among the three groups (P > 0.05). Higher percentages of adverse events were detected in groups 2 (31.3%) and 3 (25%) compared to group 1 (5.6%). However, the difference was not statistically significant (P > 0.05). All reported adverse events were gastrointestinal symptoms. Resveratrol showed a similar efficacy with HU in the small population of non-transfusion B-TI patients during a 6-month follow-up. Complications, mostly gastrointestinal, were observed more frequently in resveratrol groups compared to the HU group. Although it was not statistically significant, more attention should be given to safety and efficacy of resveratrol as an oral HbF-augmenting agent.

Blood transfusion versus hydroxyurea in beta-thalassemia in Iran: a cost-effectiveness study

ABSTRACTIntroduction: Thalassemia intermedia is a type of anemia which has several treatments modalities. We aimed to study the cost effectiveness of two treatments, including blood transfusion and hydroxyurea, in patients with beta-thalassemia intermedia in south of Iran referred to a referral center affiliated to Iran, Shiraz University of Medical Sciences in 2015.Materials and methods: This was a cost-effectiveness study which was conducted on 122 patients with beta-thalassemia intermedia. The indicator of effectiveness in this study was the reduction of growth disorder (normal BMI). Data analysis was done using SPSS 21, Excel 2010 and Treeage 2011. Finally, the one-way sensitivity analysis was performed to determine the robustness of the results.Results: The average annual costs of blood transfusion and the use of hydroxyurea in 2015 were 20733.27 purchasing power parity (PPP)$ and 7040.29 PPP$, respectively. The effectiveness of blood transfusion was57.4% while in hydroxyurea group was 60.7%.Conclusion: The results showed that the cost effectiveness of using hydroxyurea was more than that of blood transfusion. Therefore, it is recommended that the use of hydroxyurea in the treatment of patients with beta-thalassemia intermedia would become the first priority, and more basic and supplementary insurance coverage for treating such patients using hydroxyurea should be considered.