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Objective: Increased survival rate of patients with Transfusion-dependent Thalassemia (TDT) should be in line with their good quality of life (QoL). The study aimed to analyze the relationship between sociodemographic factors and clinical characteristics with the QoL of children with TDT. Methods: A cross-sectional study was conducted at Hasan Sadikin General Hospital from December 2022 to February 2023. A total of 158 eligible subjects aged 5–18 years with TDT were included in the analysis. QoL assessment was performed using child self-report and parent-proxy report questionnaires, along with physical examination findings. Bivariate and multivariate analyses were conducted to analyze the data. Results: A total of 158 subjects who met the research criteria were included in the analysis. Of 58.9% of children with TDT had a low adherence rate to iron chelating therapy (ICT). School function had the lowest score in QoL based on child-self report and parent proxy. Gender (p<0,05) and adherence to ICT (p<0,05) were significantly associated with lower quality of life. Conclusion: Female and adherence to ICT were predictors of children with TDT's QoL. [ABSTRACT FROM AUTHOR]

Background Adrenal insufficiency (AI) in hemoglobin E (HbE)/beta thalassemia, including evaluation of mineralocorticoid axis, had not been studied. Aims and Objectives In this study, we attempted to evaluate the prevalence of AI in HbE/beta thalassemia and wanted to determine if the prevalence of AI varied according to severity of HbE/beta thalassemia and transfusion requirements. Methods In this observational, cross-sectional study, 104 patients with HbE/beta thalassemia were evaluated. Among them, 57 and 47 were transfusion dependent and non-transfusion dependent. According to Mahidol criteria, patients were classified into mild (n = 39), moderate (n = 39), and severe (n = 26) disease. Early morning (8 Am) serum cortisol, plasma ACTH, and plasma aldosterone, renin were measured. Patients with baseline cortisol of 5 to 18 μg/dL underwent both 1 μg and 250 μg short Synacthen test. According to these results, patients were classified as having either normal, subclinical, or overt (primary/secondary) adrenal dysfunction. Results Adrenal insufficiency was found in 41% (n = 43). Among them 83.7% (n = 34) had primary AI and 16.3% (n = 9) had secondary AI. Thirty-three patients (31%) with normal or elevated ACTH and with low or normal aldosterone with high renin were diagnosed as having subclinical AI. There was no difference in prevalence of AI between transfusion dependent and non-transfusion dependent (P =.56) nor was there was any difference in prevalence of AI according to disease severity (P =.52). Conclusion Adrenal insufficiency is common in HbE/beta thalassemia and is independent of transfusion dependency and disease severity. [ABSTRACT FROM AUTHOR]

Background: Cardiac complications in patients with transfusion-dependent thalassemia (TDT) are one of the major causes of mortality in these patients which annually impose economic burden on the endemic countries. Heart T2 MRI is a good modality for evaluating iron overload. Our aim was to investigate the pooled correlation between the serum ferritin level and heart iron overload in TDT patients and compare the effect size in different geographical areas. Methods: PRISMA checklist was used to summarize the literature search. Three major databases were used for the papers and exported into endnote for screening. Data were extracted into an Excel spreadsheet. The data were analyzed using STATA software. CC was considered as the effect size, and the amount of heterogeneity was indicated by I-squared. Meta-regression was used for age. Also, sensitivity analysis was performed. Results: The present study showed a statistically significant negative correlation of the serum ferritin level with heart T2 MRI: -0.30 (95% CI -0.34, -25). This correlation was not significantly affected by the patients' age (p-value: 0.874). Given different geographic area, most of the studies from different countries indicated that the correlation between the serum ferritin and heart T2 MRI was statistically significant. Conclusions: The pooled analysis showed a significant negative moderate correlation between the serum ferritin level and heart T2 MRI in patients with TDT, regardless of their age. This issue underscores the importance of periodical evaluation of serum ferritin level in patients with TDT in developing countries with low financial supports and limited resources. Further studies are suggested to evaluate the pooled correlation of the serum ferritin level with iron concentration of other vital organs. [ABSTRACT FROM AUTHOR]

Abstract Background Hematopoietic stem cell transplantation (HSCT) is a treatment option with curative intent for patients with transfusion dependent thalassemia (TDT) but its application is limited by the lack of suitable donors and acceptability due to the related morbidity/mortality. Transplantation of autologous genetically modified hematopoietic cells, gene therapy (GT) is emerging as a promising treatment option for TDT as it eliminates graft versus host disease (GVHD) and need for immunosuppression. Early results of GT suggest that many, but not all patients achieve transfusion independence after the procedure. There is little information about the acceptability of GT in patients with TDT. We sought to examine patient/family knowledge about GT in TDT and to examine factors that influence decision-making about this therapy. Methods Parents of children with TDT and adults with TDT were who provided informed consent underwent semi-structured interviews to understand patient/family knowledge and decision-making regarding GT in TDT. Transcribed interviews were coded and the data was examined for emerging themes using a combination of thematic and content analysis. Results Twenty-five study participants with mean age of 38Y (17—52Y) including eight adults living with TDT, and 17 parents of children with TDT underwent semi-structured qualitative interviews. Participant responses coalesced around broad themes related to knowledge of GT, motivating/deterring factors and outcomes. Study participants expressed a desire for ‘cure’ from thalassemia including transfusion independence, chelation reduction and improved quality of life as motivators for considering GT. Insufficient knowledge about the process, long-term outcomes, safety, and side effects as well as the potential for death/failure of the procedure were deterrents for the consideration GT. Reduction in frequency of transfusions, even without elimination of transfusions was an acceptable outcome of GT for most participants. Participant choice for preferred treatment modality was split between indefinitely continuing transfusions which was familiar to them versus GT which was unfamiliar, and with an uncertain outcome. None of the participants had a matched sibling donor; alternate donor HSCT was the least preferred option in this group. Conclusion There is tempered excitement about GT in patients/families with TDT with a general willingness to accept transfusions reduction as the outcome.

Introduction: COVID-19 pandemic imposed challenges towards management of transfusion-dependent thalassemia patients (TDT). The need for regular blood transfusions and iron chelation therapy in these patients added further uncertainty about managing COVID-19 in this subset of patients. Aims: To describe the clinical manifestations of SARS-CoV2 infection in patients with TDT and to evaluate feasibility of home management for patients with mild disease. Methodology: The study involved TDT patients registered with thalassemia day care center, DMCH, who tested positive for COVID-19 by RTPCR. The demographics, clinical characteristics and baseline investigations were recorded. Patients with mild disease were managed at home and others were hospitalized. The daily home monitoring and the hospital course were noted and analyzed. Results: The study involved 14 TDT patients who were infected with SARS-CoV2 with a mean age of 18.9 ± 6.7 years and a male to female ratio of 6:1. Five patients each were in low and high-risk groups and 4 patients were in highest risk group. The symptoms reported by these patients were fever, fatigue, sore throat etc. Two patients were hospitalized with one patient requiring oxygen therapy. He was discharged after 48 hours. The other patient had severe cardiac iron overload and diabetes mellitus. His iron chelation therapy was witheld during hospitalization. He presented with a cardiac arrhythmia later and was cardioverted. Thus, all other patients were continued on iron chelation with deferasirox. Twelve patients were successfully managed at home with regular telephonic monitoring. Conclusion: Patients with thalassemia do not necessarily need hospitalization for management of COVID-19. Home management can be offered to patients with mild disease in a resourse limited setting. Iron chelation with deferasirox can be continued safely.

Introduction: COVID-19 pandemic imposed challenges towards management of transfusion-dependent thalassemia patients (TDT). The need for regular blood transfusions and iron chelation therapy in these patients added further uncertainty about managing COVID-19 in this subset of patients. Aims: To describe the clinical manifestations of SARS-CoV2 infection in patients with TDT and to evaluate feasibility of home management for patients with mild disease. Materials and methods: The study involved TDT patients registered with thalassemia day care center, DMCH, who tested positive for COVID-19 by RTPCR. The demographics, clinical characteristics and baseline investigations were recorded. Patients with mild disease were managed at home and others were hospitalized. The daily home monitoring and the hospital course were noted and analyzed. Results: The study involved 14 TDT patients who were infected with SARS-CoV2 with a mean age of 18.9 ± 6.7 years and a male to female ratio of 6:1. Five patients each were in low and high-risk groups and 4 patients were in highest risk group. The symptoms reported by these patients were fever, fatigue, sore throat etc. Two patients were hospitalized with one patient requiring oxygen therapy. He was discharged after 48 hours. The other patient had severe cardiac iron overload and diabetes mellitus. His iron chelation therapy was with held during hospitalization. He presented with a cardiac arrhythmia later and was cardioverted. Thus, all other patients were continued on iron chelation with deferasirox. Twelve patients were successfully managed at home with regular telephonic monitoring. Conclusion: Patients with thalassemia do not necessarily need hospitalization for management of COVID-19. Home management can be offered to patients with mild disease in a resource limited setting. Iron chelation with deferasirox can be continued safely.

Background: Hematopoietic stem cell transplantation (HSCT) is a treatment option with curative intent for patients with transfusion dependent thalassemia (TDT) but its application is limited by the lack of suitable donors and acceptability due to the related morbidity/mortality. Transplantation of autologous genetically modified hematopoietic cells, gene therapy (GT) is emerging as a promising treatment option for TDT as it eliminates graft versus host disease (GVHD) and need for immunosuppression. Early results of GT suggest that many, but not all patients achieve transfusion independence after the procedure. There is little information about the acceptability of GT in patients with TDT. We sought to examine patient/family knowledge about GT in TDT and to examine factors that influence decision-making about this therapy.Methods: Parents of children with TDT and adults with TDT were who provided informed consent underwent semi-structured interviews to understand patient/family knowledge and decision-making regarding GT in TDT. Transcribed interviews were coded and the data was examined for emerging themes using a combination of thematic and content analysis.Results: Twenty-five study participants with mean age of 38Y (17-52Y) including eight adults living with TDT, and 17 parents of children with TDT underwent semi-structured qualitative interviews. Participant responses coalesced around broad themes related to knowledge of GT, motivating/deterring factors and outcomes. Study participants expressed a desire for 'cure' from thalassemia including transfusion independence, chelation reduction and improved quality of life as motivators for considering GT. Insufficient knowledge about the process, long-term outcomes, safety, and side effects as well as the potential for death/failure of the procedure were deterrents for the consideration GT. Reduction in frequency of transfusions, even without elimination of transfusions was an acceptable outcome of GT for most participants. Participant choice for preferred treatment modality was split between indefinitely continuing transfusions which was familiar to them versus GT which was unfamiliar, and with an uncertain outcome. None of the participants had a matched sibling donor; alternate donor HSCT was the least preferred option in this group.Conclusion: There is tempered excitement about GT in patients/families with TDT with a general willingness to accept transfusions reduction as the outcome. [ABSTRACT FROM AUTHOR]

IntroductionCo-inheritance of hereditary hemochromatosis (HFE) gene variants p. C282Y and p.H63D worsen iron overload in transfusion-dependent thalassemia. Data on the HFE gene variants in Sri Lankan patients with thalassemia have not been extensively studied. This study aimed to analyze the p.C282Y and p.H63D variants in transfusion-dependent beta (β) and HbE/β-thalassemia patients and establish an association between these variants and their serum ferritin levels.Materials and MethodsA total of 125 transfusion-dependent β-thalassemia major and HbE/β thalassemia patients were tested for the c.845G>A (p.C282Y) and c.187C>G (p.H63D) HFE gene variants using the multiplex Amplification Refractory Mutation System Polymerase Chain Reaction method. For phenotype-genotype correlation, serum ferritin levels, the erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured. The standard descriptive statistics were used for data analysis.ResultsThe study cohort consisted of transfusion-dependent 123 β-thalassemia and 2 HbE/β-thalassemia patients. The p.C282Y variant was not detected in any patient; allele frequency for the wild type (c.845GG) was 100%. Twenty-three patients were heterozygous for the p.H63D variant allele, and the allele frequencies were c.187CC 91.8%, c.187CG 9.2%, and c.187GG 0%. The mean serum ferritin level was relatively higher (mean level 4,987 ng/ml) in the p.H63D heterozygous (c.187CG) group compared to the wild type (c.187CC) group (mean level 4,571 ng/ml), but the difference was statistically not significant (p = 0.865). Among the total study population, CRP, ESR, and serum glutamine aspartate transaminase (SGPT) were elevated in 9 (7.2%), 65 (52%), and 82 (65.6%) patients, respectively. Among the p.H63D c.187CG group, elevated CRP, ESR, and SGPT were present in 5 (5%), 15 (12%), and 18 (14.4%) patients, respectively. The detected sample number was low to correlate with the confounding effect of inflammatory disorders and liver damage on the serum ferritin levels.ConclusionsThe HFE gene variant p.C282Y is unlikely to cause iron overload in the Asian β-thalassemia patients; the rarity of this variant in the study cohort replicates the findings of other South Asian population studies of this variant. The presence of the p.H63D variant could be a potential risk factor for iron overload in the β-thalassemia patients. A more extensive cohort study is required to validate this finding.

Shaema Amin,1 Sana Jalal,2 Kosar Ali,3 Luqman Rasool,4 Tara Osman,4 Omed Ali,5 Abdalhamid M-Saeed4 1Hiwa Hematology/Oncology Sulaymaniyah Cancer Center, Sulaymaniyah, Iraq; 2Department of Pathology, College of Medicine, University of Sulaymaniyah, Sulaymaniyah, Iraq; 3Department of Medicine, College of Medicine, University of Sulaymaniyah, Sulaymaniyah, Iraq; 4Thalassemia and Congenital Blood Disorders Center, Sulaymaniyah, Iraq; 5Otolaryngology Head and Neck Surgery Center, Sulaymaniyah Teaching Hospital, Sulaymaniyah, IraqCorrespondence: Shaema AminHiwa Hematology/Oncology Sulaymaniyah Cancer Center, Sulaymaniyah, IraqTel +964-7701499546Email shaema.salih.amin@gmail.comBackground: β-thalassemia is a significant problem in the northeastern part of Iraq, and has imposed a huge burden on the health authorities.Objective: To identify the molecular characterization and morbidity prevalence in transfusion-dependent thalassemia (TDT) and non-transfusion dependent thalassemia (NTDT) phenotypes in northeastern Iraq.Patients and Methods: This is a cross-sectional study conducted on 242 β-thalassemia patients from 162 families. Reverse hybridization technique and direct gene sequencing were used to characterize β-thalassemia mutations, and medical records of the patients were reviewed with a well-designed questionnaire.Results: A total of 22 β-globin mutations arranged in 53 different genotypes were identified: IVS-II-1 (G> A) (35.7%), followed by IVS-I-6 (T> C) (18.0%), and codon 8/9 (+G) (8.5%) were the most frequent. Among disease-related morbidities, bone disease amounted to (66.9%), followed by endocrinopathies (32.2%), hepatobiliary complications (28.9%), and pulmonary hypertension (9.9%), whereas thrombosis, extramedullary hemopoiesis, and leg ulcers were less frequent.Conclusion: The overall complications rate was 78.9%, with a growing probability of complications with advanced age, with evidently higher rates in patients with β0β0 and β0β+ genotypes that explain the role of underlying genetic defects in the pathophysiology of disease complications.Keywords: transfusion dependent thalassemia, non-transfusion dependent thalassemia, HBB mutations, morbidities, risk factors, Iraq

Abstract Background Thalassemia is a hereditary hemolytic anemia with a severity ranging from mild, non-transfusion dependent to severe chronic anemia requiring lifelong transfusion. Transfusional iron overload is a major complication in patients with transfusion-dependent thalassemia (TDT). Telomeres are sequences of nucleotides forming the end caps of chromosomes that act as a DNA repair system. Iron overload in thalassemia can cause increased oxidative stress which leads to cellular damage and senescence. This may result in telomere length shortening. The degree of telomere length shortening may reflect the severity of thalassemia. Methods This research aimed to study the leukocyte telomere length in patients with TDT in comparison to non-thalassemic individuals and to identify the clinical and laboratory parameters that are associated with telomere length. We conducted a cross-sectional study in patients with TDT aged ≥18 years. Leukocyte telomere length was measured by real-time quantitative PCR. Results Sixty-five patients with TDT were enrolled onto the study. There were 37 female patients (54.4%). The median age was 27 (18–57) years, and mean pre-transfusion hemoglobin level was 7.1 (± 1.07) g/dL. The mean telomere to single copy gene (T/S) ratios of patients with TDT and the controls were 0.72 ± 0.18 and 0.99 ± 0.25, respectively (p

Background: Hypertriglyceridemia thalassemia syndrome (HTS) is not a well understood entity, and is mainly identified in the Indian subcontinent. We present a unique case of this syndrome along with severe autoimmune haemolysis that presented with life-threatening anaemia. Observations: An infant with transfusion dependent thalassemia (TDT) presented with suspected mismatched blood transfusion leading to severe haemolysis. Severe haemolysis, lipemic serum were initial findings. Detailed evaluation revealed IgG, C3d positive mixed autoimmune haemolytic anaemia (AIHA), severe hypertriglyceridemia that improved with steroids and least mismatched packed red cell transfusion. Conclusion: Children with thalassemia presenting with excessive hemolysis may have mismatched transfusion reaction, alloimmunization or an autoimmune hemolysis. Baseline extended blood grouping, detailed immune hemolytic work-up aids in prompt diagnosis. HTS on a background of autoimmune hemolysis is rare and needs urgent medical support.

To evaluate any association between pre-transfusion hemoglobin (Hb) levels and thalassemia complications and to identify the Hb cutoff values to predict thalassemia complications. We performed a cross-sectional study in thalassemia patients who attended the Adult Hematology Clinic of the tertiary care University Hospital from October 2017 to October 2018. A point-biserial correlation was used to identify any association between Hb levels and thalassemia complications. A receiver operating characteristic (ROC) curve was used to identify the diagnostic ability of Hb levels to predict thalassemia complications and identify Hb cutoff values. Out of the 102 patients, there were 53 transfusion dependent thalassemia (TDT) patients and 49 non-transfusion dependent thalassemia (NTDT) patients. In theTDT group, Hb levels showed a negative correlation with severe hepatic iron overload and hypogonadism. The cutoff Hb levels to predict severe hepatic iron overload and hypogonadism were ≤7.01 and 6.81 g/dL, respectively, at which points the area under the ROC curve (AUC) were 0.721 and 0.708, respectively. In the NTDTgroup, Hb levels were negatively correlated with hepatic iron overload, osteoporosis, and pulmonary hypertension. The cutoff values of Hb levels to predict hepatic iron overload, osteoporosis, and pulmonary hypertension were ≤8.24, 7.16, and 7.16 g/dL, respectively, at which points the AUC were 0.923, 0.715, and 0.725, respectively. Lower Hb level was associated with more frequent complications in both TDT and NTDT patients. The Hb cutoff levels to predict these complications were identified. [ABSTRACT FROM AUTHOR]

Early mixed chimerism (MC) can lead to secondary graft rejection post allogeneic hematopoietic stem cell transplantation in transfusion dependent thalassemia (TDT) patients. Reduction of immunosuppression and donor lymphocyte infusions is the mainstay for treating MC. We report our experience of administering unmanipulated stem cell boost (SCB) in reversing progressive early MC. There were 70 transplants done for 69 TDT patients at our center between September 2005 and January 2020. Mixed chimerism was defined by > 5% recipient cells and the severity was assigned according to the proportion of recipient cells as level 1 = < 10%, level 2 = 10–25%, level 3 = > 25%. For patients developing MC level 2 and 3, we administered unmanipulated SCB and analyzed its safety and efficacy. Out of 70 transplants 7 (10%) had MC level 2 (3/7) and 3 (4/7). These patients received unmanipulated SCB at a median CD34 cell dose of 4.5 × 106/kg (range—3.5 × 106/kg–5.5 × 106/kg). Overall Response (stable MC and/or transfusion independency) to unmanipulated SCB was seen in 5 patients (71.4%). Five patients (71.4%) developed acute graft versus host disease (GVHD) of which 1 patient expired due to severe GVHD. SCB infusion was well tolerated by majority of our patients. The 3 year overall survival and thalassemia free survival was 85.7% (6/7) and 57.1% (4/7) respectively. Timely monitoring of chimerism is important for detecting early MC. Development of acute GVHD is common after administration of unmanipulated SCB and requires vigilance and prompt management. Unmanipulated SCB is a feasible modality for treating progressive MC and salvaging the graft especially in resource-constrained settings. [ABSTRACT FROM AUTHOR]

Background: Thalassemia is a chronic disease requiring lifelong treatment. The adherence to regular iron chelation therapy is important to ensure complication-free survival and good quality of life. The study aim to assess the adherence to iron chelation therapy (ICT) in patients with transfusion-dependent thalassemia (TDT), evaluate various causes of non-adherence and study the impact of non-adherence on the prevalence of complications secondary to iron overload. Materials and Methods: Patients with TDT on ICT for > 6 months were enrolled in the study. Hospital records were reviewed for demographic details, iron overload status, treatment details, and the prevalence of complications. A study questionnaire was used to collect information on adherence to ICT, knowledge of patients, and the possible reasons for non-adherence. Results: A total of 215 patients with a mean age of 15.07+7.68 years and an M: F ratio of 2.2:1 were included in the study. Non-adherence to ICT was found in 10.7% of patients. Serum ferritin levels were significantly higher in the non-adherent group (3129.8+1573.2 µg/l) than the adherent population (2013.1+1277.1 µg/l). Cardiac as well as severe liver iron overload was higher in the non-adherent patients. No correlation was found between disease knowledge and adherence to ICT. Difficulties in drug administration and many medicines to be taken daily were statistically significant reasons for non-adherence. There was no difference in the co-morbidities arising due to the iron overload in the two groups. Conclusion: Nearly 11% of patients with TDT were non-adherent to ICT. Non-adherence results in higher iron overload.

Background: Thalassemia is a hereditary hemolytic anemia with a severity ranging from mild, non-transfusion dependent to severe chronic anemia requiring lifelong transfusion. Transfusional iron overload is a major complication in patients with transfusion-dependent thalassemia (TDT). Telomeres are sequences of nucleotides forming the end caps of chromosomes that act as a DNA repair system. Iron overload in thalassemia can cause increased oxidative stress which leads to cellular damage and senescence. This may result in telomere length shortening. The degree of telomere length shortening may reflect the severity of thalassemia. Methods: This research aimed to study the leukocyte telomere length in patients with TDT in comparison to non-thalassemic individuals and to identify the clinical and laboratory parameters that are associated with telomere length. We conducted a cross-sectional study in patients with TDT aged ≥18 years. Leukocyte telomere length was measured by real-time quantitative PCR. Results: Sixty-five patients with TDT were enrolled onto the study. There were 37 female patients (54.4%). The median age was 27 (18–57) years, and mean pre-transfusion hemoglobin level was 7.1 (± 1.07) g/dL. The mean telomere to single copy gene (T/S) ratios of patients with TDT and the controls were 0.72 ± 0.18 and 0.99 ± 0.25, respectively (p < 0.0001). There was a significant correlation between the T/S ratio and age (p = 0.0002), and hemoglobin level (p = 0.044). There was no correlation between telomere length and other factors. Conclusions: Our study showed that TDT patients had shorter leukocyte telomere length compared with controls. Leukocyte telomere shortening in TDT was an aging-dependent process and associated with lower hemoglobin level. [ABSTRACT FROM AUTHOR]

To test the postulated hypothesis that splenectomy may influence the development of Hypothyroisdism (HT) in Transfused Dependent Thalassemia (TDT) young patients, basic factors known to influence the development of hypothyroidism were evaluated in 52 TDT adult patients (25 splenectomized) with HT. Precise analysis of data not only failed to disclose any statistical differences but revealed similarities, between splenectomized and non- splenectomized patients in respect to: i) the age at diagnosis of HT and ii)the ferritin levels on diagnosis and at the year of study. Interestingly a statistically higher age at diagnosis was recorded in central HT irrespective of splenectomy.

In this cross-sectional study we assessed the vascular alterations in retinal and choriocapillaris perfusion in patients affected by β-thalassemia, by means of optical coherence tomography angiography (OCTA). A total of 124 eyes of 62 patients (mean age 44.74 ± 5.79 years old) affected by β-thalassemia (transfusion dependent thalassemia (TDT), non-transfusion dependent thalassemia (NTDT) and minor) were compared to 40 eyes of twenty healthy subjects. We evaluated the vessel density (VD) in superficial capillary plexus, deep capillary plexus, radial peripapillary capillary, choriocapillaris and the foveal avascular zone area. The TDT group showed a statistically significant reduction in retinal and choriocapillaris VD respect to controls and the other groups (p < 0.05). No statistically significant difference was found in OCTA parameters between β-thalassemia minor and controls. The NTDT group showed a significant reduction in VD in deep capillary plexus respect to controls and β-thalassemia minor. Significant negative correlations were shown in TDT group between foveal avascular zone and hemoglobin (r = −0.437, p = 0.044) and between ferritin levels and VD of choriocapillaris (r = −0.431, p = 0.038). The OCTA parameters provided a deeper understanding on retinal and choriocapillaris vascular impairment affected by tissue hypoxia levels and the oxidative stress in different clinical phenotypes of the β-thalassemia.

This study aimed to determine the potential iron-chelating effects of silymarin in patients with β-thalassemia major receiving standard iron-chelation therapy. We evaluated whether addition of silymarin to standard iron-chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo-controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other groups. Silymarin efficacy was assessed by measuring serum iron level, ferritin level, total iron-binding capacity and liver and cardiac function on magnetic resonance imaging. Silymarin treatment resulted in a negative change in the serum iron and ferritin levels and a positive change in the total iron-binding capacity levels (treatment effect, p < .001, p = .06, and p = .05, respectively). Silymarin treatment led to positive changes in cardiac and liver function in both treatment sequences of study; however, this was not statistically significant. There was a negative change in liver iron concentration in both treatment sequences (treatment effect, p = .02). In conclusion, combined iron-chelation and silymarin therapy was effective for improving the iron-burden status in patients with β-thalassemia major. [ABSTRACT FROM AUTHOR]

Iron overload (IOL) is highly prevalent among patients with hemoglobinopathies; both transfusion dependent thalassemia (TDT) and non-transfusion dependent thalassemia (NTDT). Whether IOL is secondary to regular transfusions like in TDT, or develops from increased intestinal absorption like in NTDT, it can cause significant morbidity and mortality. In TDT patients, iron accumulation in organ tissues is highly evident, and leads to organ toxicity and dysfunction. IOL in NTDT patients is cumulative with advancing age, and concern with secondary morbidity starts beyond the age of 10 years, as shown by the OPTIMAL CARE study. Several modalities are available for the diagnosis and monitoring of IOL. Serum ferritin (SF) assessment is widely available and heavily relied on in resource-poor countries. Non-invasive iron monitoring using MRI has become the gold standard to diagnose IOL. Three iron chelators are currently available for the treatment of IOL: deferoxamine (DFO) in subcutaneous or intravenous injection, oral deferiprone (DFP) in tablet or solution form, and oral deferasirox (DFX) in dispersible tablet (DT) and film-coated tablet (FCT). Today, the goal of ICT is to maintain safe levels of body iron at all times. Appropriate tailoring ICT with chelator choices and dose adjustment must be implemented in a timely manner. Clinical decision to initiate, adjust and stop ICT is based on SF, MRI-LIC and cardiac T2*. In this article, we review the mechanism of IOL in both TDT and NTDT, the pathophysiology behind it, its complications, and the different ways to assess and quantify it. We will also discuss the different ICT modalities available, and the emergence of novel therapies. [ABSTRACT FROM AUTHOR]

Thalassemias are emerging as a global public health concern. Due to remarkable success in the reduction of childhood mortality by controlling infectious diseases in developing countries, thalassemias are likely to be a major public health concern in the coming decades in South Asia. Despite the fact that Bangladesh lies in the world's thalassemia belt, the information on different aspects (epidemiology, clinical course, mortality, complications and treatment outcomes) of thalassemias is lacking. In this comprehensive review, the aim is to to depict the epidemiological aspects of thalassemias, mutation profile and current treatment and management practices in the country by sharing the experience of dealing with 1178 cases over 2009-2014 time periods in a specialized thalassemia treatment centre. We have also discussed the preventative strategies of thalassemias from the context of Bangladesh which could be effective for other developing countries. [ABSTRACT FROM AUTHOR]

To study clinical and echocardiographic parameters in Transfusion Dependent Thalassemia (TDT) patients, correlating them with T2*CMRI. To identify features of Speckle Tracking Echocardiography (STE) in those with severe TDT to prioritize patients in need of early T2*CMRI and aggressive chelation. Hemosiderosis from life-long transfusions in TDT is amplified in Low- and Middle-Income Countries (LMIC) when access to resources may be scarce, delaying timely chelation. T2* imaging is the gold standard to non-invasively estimate myocardial iron and guide therapy. In resource constraint areas, we propose use of STE to prioritize those with severe disease to obtain early T2* CMRI. TDT patients (N = 25) who underwent clinical, echocardiographic, and CMRI evaluation were included, with recruitment of age matched controls. Echocardiographic indices of ventricular function and strain were correlated with T2*. Severe disease was defined as T2* < 10 ms. Differences among patients with severe disease and controls were analyzed in addition to differences between those with normal and abnormal T2*. There was moderate (R −0.60, p = 0.002) inverse correlation between T2* and peak systolic global longitudinal strain (GLS) and regional basal strain (R −0.62, p < 0.001) indicating these parameters were lower in patients with severe disease when compared with controls and non-severe TDT group. GLS and most indices of regional strain were lower in patients with severe disease (T2* < 10 ms) when compared with the control group (p < 0.05). The Apex- base ratio reached significance (p = 0.02) in patients with abnormal T2*(<20 ms) when compared with normal T2*(<20 ms) in TDT positive patients. Early decrease in global and regional strain can serve as a useful tool to identify patients with severe TDT before reduction in ejection fraction. This study makes a case for utilizing STE as an adjunct or initial screen to T2* CMRI in LMIC to prioritize patients in need of T2*CMRI to facilitate aggressive iron chelation protocols. • Hemosiderosis from life-long transfusions in Transfusion Dependent Thalassemia (TDT) is amplified in Low- and Middle-Income Countries (LMIC) when access to resources maybe scarce, delaying timely chelation. • T2* imaging is the gold standard to non-invasively estimate myocardial iron and guide therapy. However, a dedicated CMRI machine with T2* capabilities is limited in LMIC areas in comparison to the global reach of echocardiography • Our study found a decrease in global and regional strain despite normal ejection fraction in patients with severe TDT • The Apex-base strain ratio was significant in patients with abnormal T2* vs normal T2* in TDT patients • In resource constraint areas, we propose use of Speckle Tracking Echocardiography (STE) to prioritize those with severe disease to obtain early T2* CMRI. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is associated with significant morbidity and shortened life expectancy. Similarly, patients with transfusion dependent beta thalassemia (TdT) require life-long transfusion therapy, chelation therapy and significant organ dysfunction. Allogeneic transplantation from a matched family donor provided the only curative option for patients with SCD and TdT. Unfortunately, less than 20% of patients have a fully matched related donor and results using unrelated donor transplant were associated with high rate of complications. Ex vivo gene therapy through globin gene addition has been investigated extensively and recent encouraging preliminary data resulted in regulatory approval in patients with TdT. Recent improvements in our understanding of the molecular pathways controlling erythropoiesis and globin switching from fetal hemoglobin to adult hemoglobin offer a new and exciting therapeutic options. Rapid and substantial advances in genome editing tools using CRISPR/Cas9, have raised the possibility of genetic editing and correction in patient derived hematopoietic stem and progenitor cells. We will review results of gene editing approach that can induce fetal hemoglobin production in patients with SCD and TdT., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Beta thalassemia major, one of the most prevalent hemoglobinopathy throughout the word, can be cured by allogenic stem cell transplantation (SCT) (Bone Marrow Transplant 36:971-975, ). Many patients, however, lack a suitably matched related sibling donor. Unrelated umbilical cord blood (UCB) can be used as an alternative stem cell source for these patients. This report describes SCT for nine children with beta-thalassemia major using partially HLA-matched unrelated UCB. Conditioning included oral busulfan 16 mg/kg (day −10 to −7), cyclophosphamide (Cy) 200 mg/kg (day −5 to −2), fludarabine 90 mg/kg (day −13 to −11), and antithymocyte globulin (rabbit) 7.5 mg/kg (day −3 to −1). The infused cell dose was 10.71 × 10/kg total nucleated cells (TNC) (range 6.5-17 × 10/kg TNC). The patients ranged in age from 1.5 to 7 years, in weight from 10.5 to 17 kg. A second transplant with two unrelated cord blood units was attempted in two patients who had primary graft failure. The retransplant recipients were preconditioned with i.v Cy 120 mg/kg (day −3 to −2). Five of the nine patients engrafted promptly with 50-100 % donor chimerism (56 %). They engrafted at a median of 17 days (range 12-19). One patient is transfusion free for 36 months; a second patient is transfusion free for 18 months and a third is transfusion free for 9 months. There was no transplant related mortality. Four of the nine children had autologous recovery without engraftment. Primary graft rejection is the major complication. Post transplant complications were mild hepatic veno-occlusive disease, acute GVHD grade II, and CMV interstitial pneumonia. The chronic GVHD was limited and could be controlled by Methylprednisolone combined with Mycophenolate. The lack of a marrow donor registry in India makes UCBT from related and unrelated donors a good alternative. Transplant should be delayed until the child is at least 18 months of age. The dose of UCB stem cells is the most important factor for engraftment. UCB has the advantages of rapid availability and low risk of severe GVHD despite donor-recipient HLA disparity (Transplant Proc 37:2667-2669, ). We demonstrate the feasibility of this procedure in the setting of a developing country. [ABSTRACT FROM AUTHOR]