Search Results (142)

Background: Iron overload and its associated complications are major concerns in patients with transfusion-dependent β-thalassaemia (TDT). Iron chelation is an important part of TDT therapy with monotherapy or dual iron chelation being the most commonly used strategies. Evidence regarding the efficacy and safety of triple iron chelation therapy remains limited. Case presentation: We present the case of a 21-year-old immigrant from the Middle East with TDT and a history of irregular transfusion management without chelation therapy, leading to clinically significant iron overload. She was successfully treated with the combination of deferoxamine, deferasirox and deferiprone over a course of 8 years. Triple chelation therapy led to sustained reductions in serum ferritin levels and improvement in hepatic and cardiac iron burden on follow-up MRI, with good tolerability. Conclusions: This case highlights the potential role of triple iron chelation therapy as a therapeutic strategy in TDT patients with severe iron overload. Further studies are needed to establish optimal dosing, eligible patients and long-term safety. Full article

Background/Objectives: Transfusion-dependent β-thalassaemia (TDT) is a lifelong condition requiring coordinated multidisciplinary care. In France, where the disease is rare, transition from pediatric to adult care remains poorly structured, potentially compromising adherence and long-term outcomes. Methods: This national retrospective study evaluated current transition practices and their clinical impact among young adults with TDT. Patients aged 20–25 years in December 2022 were identified from the national NaThalY registry. Those diagnosed and managed in France before age 15 were included. Clinical data were collected for the two years preceding and following transition. Transition practices were assessed using a standardized questionnaire sent to pediatric centers. Results: Thirty-four patients were included (mean transition age: 19 years). The rate of response to the questionnaire was 90.5%, with feedback from 19 centers. Only one-third of centers offered joint pediatric–adult consultations, and one-quarter provided transition-focused education. No written transition protocols were reported. Mean pre-transfusion hemoglobin levels were significantly lower after the transition (8.5 vs. 8.0 g/dL; p = 0.01). Ferritin levels showed a non-significant increase, with no statistically significant changes observed in hepatic or cardiac iron concentrations. Conclusions: This study demonstrates marked heterogeneity and limited formalization of transition practices in France. Development of structured, standardized transition pathways is urgently needed to ensure continuity of care and optimal disease management in adults with TDT. Full article

Background and Objective: Iron overload remains a significant clinical concern in patients with transfusion-dependent beta-thalassemia (TDT). This study aims to characterize the iron load and endocrine profile of adult transfusion-dependent beta-thalassemia patients and to evaluate their correlation with growth retardation. Methods: A cross-sectional study was conducted at PIMS Hospital, Islamabad, involving 62 adult patients with homozygous or HbE beta-thalassemia receiving regular blood transfusions. Iron overload was assessed using serum ferritin (SF) and transferrin saturation (TS), while endocrine function was evaluated through measurements of thyroid-stimulating hormone-sensitive (TSH), free thyroxine (FT4), and insulin-like growth factor-1 (IGF-1). Data was analyzed using SPSS v26.0 and R v4.3.1, which included Pearson correlation, chi-square testing, and multivariable regression to explore associations between iron indices and endocrine dysfunction. Results: Serum ferritin demonstrated significant negative correlations with FT4 (r = −0.348, p = 0.005) and IGF-1 (r = −0.302, p = 0.015). MRI T2* pancreas values correlated positively with FT4 (r = 0.268, p = 0.037) and IGF-1 (r = 0.312, p = 0.015). Patients with ferritin > 5000 ng/mL exhibited a higher prevalence of low IGF-1 levels (89.2% vs. 64.0%, p = 0.018). No significant gender-based differences were observed in endocrine parameters. Conclusion: Pancreatic iron burden and elevated serum ferritin were significantly associated with impaired thyroid and growth axis function, highlighting the value of integrating MRI T2* and biochemical markers for early endocrine risk stratification in adult TDT patients. Full article

The autonomic nervous system (ANS) plays a key role in cardiovascular regulation by maintaining hemodynamic and metabolic homeostasis through balanced sympathetic and parasympathetic activity. While autonomic dysfunction is classically associated with diabetes, neurodegenerative diseases, autoimmune neuropathies, and chronic cardiovascular conditions, growing evidence suggests that disturbances in iron metabolism represent an underrecognized contributor to cardiac autonomic dysregulation. This narrative review summarizes data from 107 studies on ANS disorders, including 49 investigating cardiovascular involvement. Reported abnormalities included reduced heart rate variability and baroreflex sensitivity, prolonged P-wave duration and QT dispersion, and deviations in non-invasive autonomic testing parameters. In iron overload states, these changes appear to be driven primarily by oxidative stress, whereas in iron deficiency they are likely mediated by tissue hypoxia. Importantly, several studies indicate that normalization of iron homeostasis may partially reverse autonomic dysfunction. This potentially reversible component underscores the clinical relevance of screening for and correcting iron imbalance not only to improve hematological status but also to reduce cardiovascular risk. Large-scale, multicenter studies using standardized autonomic assessment protocols are required to clarify prognostic implications and inform evidence-based clinical guidelines. Full article

β-thalassemia and sickle cell disease are two inherited hematological diseases due to defective hemoglobin synthesis or to the production of hemoglobin with altered properties. These two conditions have prolonged survival with modern support therapies, albeit life-long, complex, expensive and resource-consuming. Studies carried out in the last three decades have shown that allogeneic hematopoietic stem cell transplantation (allo-HSCT) and gene therapy may offer a curative approach for these diseases. Allo-HSCT should be performed early in life to reduce disease-related complications like irreversible tissue damage due to iron overload in patients with transfusion-dependent β-thalassemia (TDT) and systemic vasculopathy in patients with sickle cell disease (SCD). HSCTs from a matched-sibling donor or a matched-unrelated donor represent the best therapeutic option; however, haploidentical HSCT in both TDT and SCD is now increasingly performed as a valuable and viable option for a larger number of these patients. An alternative curative strategy is based on gene therapy. These curative approaches, particularly those of gene therapy, are available only in a part of the world. Gene therapy diffusion is strongly limited by its high technological and infrastructure requirements and its very high cost. Criteria must be defined for the optimal selection of TDT and SCD patients for allo-HSCT or gene therapy. Full article

Background: Haemoglobinopathies such as beta-thalassemia (β-thal), alpha-thalassemia (α-thal) and sickle cell disease (SCD) are characterised by pathogenic gene variations (mutations) in the globin genes. Patients with haemoglobinopathies have the same disease-causing coding variations with very different disease phenotypes, from requiring blood transfusions to being non-symptomatic. The gap between the expected clinical outcomes based on primary coding mutations (the genotype) and the actual observed symptoms (the phenotype) often remains unexplained. We refer to the contribution of secondary genetic modifiers—specifically, non-coding variants of the genome that alter globin gene expression and pathophysiology—as the “missing heritability” of the clinical presentation [Primary Mutation + Missing Heritability (Non-Coding Variants) = Actual Clinical Phenotype]. Objectives: This systematic review aims to find evidence connecting genetic differences outside of the protein-coding region, as in promoters, enhancers or untranslated regions (UTRs), to the clinical severity (phenotype) of beta-thalassemia, alpha-thalassaemia and SCD. We summarise the molecular basis of phenotypic variation among haemoglobinopathy patients with identical variations to reveal their missing heritability and to enhance our understanding of prognostic strategies. Methods: This systematic review was performed in accordance with the PRISMA 2020 guidelines. We used search terms related to haemoglobinopathies, non-coding variation, SNP, promoters, enhancers and clinical severity to search major databases (PubMed and Google Scholar) as of October 2025. A total of 527 (out of 572) abstracts were fit for initial screening to identify the eligible reports. Due to heterogeneity in study designs and reported outcomes, findings were synthesised descriptively and grouped by variant mechanism (cis-acting and trans-acting). The final analysis included 89 articles that demonstrated a direct association between a non-coding genomic variant and a quantitative measure of clinical severity. Results: Two main groups of non-coding variants (NCVs) that modulate foetal haemoglobin (HbF) induction were identified. The first major group comprises cis-acting variants within globin gene clusters (HBG2 promoter XmnI polymorphism, HBB promoter mutations and α-globin enhancer variants), while the second major group comprises trans-acting quantitative trait loci (QTLs) (BCL11A and HBS1L-MYB loci). Non-globin NCVs in the UGT1A1 promoter were also found to influence the severity measures in β-thal and SCD. NCVs primarily alter the binding of transcription factors and the looping dynamics of chromatin, modulating the α/β chain balance ratio and γ-globin repression. The XmnI polymorphism is the most prominent cis-acting modifier associated with β-thal intermedia. The promoter polymorphisms in TNF-α and VCAM1 are associated with vascular complications in SCD. Conclusions: NCVs are fundamental when determining the clinical measures of haemoglobinopathies, in addition to coding variants. NCV screening should be integrated for clinical prognosis for the accurate prediction of haemoglobinopathy severity and associated high-risk complications. NCVs may represent promising targets for next-generation gene editing and therapeutic intervention strategies aimed at modifying the severity of β-thal, α-thal and SCD. Full article

Background/Objectives: Thalassemia is highly prevalent in Indonesia, and its treatment imposes a significant financial burden. To date, thalassemia management in Indonesia remains largely limited to supportive therapies. This report aims to present the monitoring of the first Indonesian pediatric thalassemia patient to undergo gene therapy. Methods: Medical summaries were gathered across multiple time points. The gene therapy process consisted of several phases: screening, apheresis and cell manufacturing, conditioning, cell infusion, and post-treatment follow-up. The therapy utilized autologous CD34+ hematopoietic stem and progenitor cells (HSPCs), which were genetically modified using a lentiviral vector carrying the beta-globin gene. The primary outcome of this study was transfusion independence, determined through serial assessments of hematological parameters over a six-month period following gene therapy. Results: A 15-year-old female had been diagnosed with thalassemia major at the age of five. DNA analysis revealed compound heterozygous mutations Hb Malay (codon 19, AAC^Asn > AGC^Ser) and IVS1-nt5 (G > C). She had been receiving regular blood transfusions every 3–4 weeks, and hemosiderosis was detected in the liver and pancreas. Given the patient’s age—over 10 years—hematopoietic stem cell transplantation carries increased risks, making gene therapy the most suitable curative option. During the six-month follow-up period after gene therapy, the patient remained transfusion-independent and experienced no complications. Conclusions: In selecting an appropriate curative therapy for thalassemia patients, several factors must be considered. The successful implementation of the first gene therapy in an Indonesian pediatric thalassemia patient should serve as a catalyst for the continued development and expansion of curative treatment options for thalassemia patients across the country. Full article

Background/Objectives: Sickle cell disease (SCD) and β-thalassemia are autosomal recessive disorders of erythroid cells due to gene mutations occurring at the level of the β-globin gene. The severe forms of these hemoglobinopathies observed in individuals homozygous for these defective genes need intensive treatments, are associated with a poor quality of life, and allogeneic hematopoietic stem cell represents the only curative treatment option that can be offered to a limited proportion of patients. Methods: This work is a narrative review supported by a systematic literature search and analysis. Results: To bypass this limitation, autologous hematopoietic stem cell transplantation has been developed in these patients, in which patients’ HSCs are harvested and genetically modified ex vivo, then transplanted back into patients after conditioning for stem cell transplantation. There are two different approaches for gene therapy of hemoglobinopathies, one based on gene addition or gene silencing using lentiviruses as vectors and the other based on gene editing strategies using CRISPR-Caspase 9 technology or base editing. Several gene therapy products have been successfully evaluated in these patients, achieving transfusion independence and correction of hematological abnormalities durable over time. Conclusions: Several gene therapy products have been approved for the treatment of SCD and β-thalassemic patients and offer potentially curative treatment for these patients. Full article

Background: Pediatric patients with beta-thalassemia (BT) face unique immunologic challenges due to chronic transfusions and viral exposure. Hepatitis C virus (HCV), a common infection in polytransfused individuals, may influence immune polarization. However, the combined effect of chronic HCV and host immunogenetics on allergic sensitization remains incompletely understood. Objective: To assess total serum IgE levels and allergic manifestations in HCV-positive vs. HCV-negative BT patients, and explore associations with common polymorphisms in IL10, TLR7, IL4, and IFNG genes Methods: This cross-sectional observational study enrolled 46 BT patients (37 HCV-positive, 9 HCV-negative) and 50 healthy controls. Clinical allergy history, total IgE levels (ELISA), and skin prick tests (SPT) for aeroallergens were collected. Genotyping for IL10 −1082, TLR7 rs179008, IL4 −589, and IFNG +874 polymorphisms was performed. Associations between genotypes, HCV status, and IgE levels were analyzed descriptively due to small sample size Results: HCV-positive BT patients had lower mean IgE levels (18.73 ± 4.2 IU/mL) and fewer reported allergic symptoms (21.6%) compared to HCV-negative counterparts (118.76 ± 7.9 IU/mL; 55.5%). The IL10 −1082 AA and TLR7 rs179008 TT genotypes were more common in the HCV-positive group and were associated with lower IgE levels. No associations were noted for IL4 or IFNG variants. Splenectomy appeared to further modify IgE levels in HCV-negative patients. Due to limited power and absence of multivariate analysis, findings are exploratory. These preliminary observations may inform future studies of immune deviation in chronically infected pediatric cohorts. Conclusions: Chronic HCV infection may contribute to immune tolerance and reduced allergic expression in BT patients, potentially modulated by IL10 and TLR7 genotypes. Further studies with functional immune profiling and larger cohorts are required. Full article

Chronic anemia is commonly diagnosed in older adults and serves an important indicator of both reactive and clonal conditions. Many underlying diseases, such as myelodysplastic syndromes and multiple myeloma, are more prevalent amongst the elderly, while novel therapeutic approaches have transformed pediatric disorders of poor prognosis, such as beta-thalassemia, to a chronic disease of older adults. Thus, the increasing prevalence of chronic anemia in older ages is largely attributed to more frequent diagnostic and therapeutic evaluations and demographic changes. The etiology of anemia in adults is complex, ranging from genetic mutations to bone marrow failure syndromes, chronic kidney disease, nutritional deficiencies, and inflammatory processes, while in some cases no clear etiology is found. For this reason, extensive research is ongoing to introduce novel therapeutic targets and improve quality of life. Management of anemia in adults depends on severity and especially on the underlying conditions of each patient. Metabolic pathway analyses have revealed alterations in various pathways, including glycolysis, pyruvate, propanoate, glycerophospholipid, galactose, fatty acid, starch, and sucrose metabolism along with fatty acid elongation in mitochondria, glycerolipid, glyoxylate, and dicarboxylate metabolism in adult patients with chronic anemia compared to healthy individuals, which may serve as potential new therapeutic targets. In this review, we aim to (i) summarize current evidence regarding metabolic disturbances in diseases of age-related hematopoietic dysregulation, being represented by multiple myeloma and myelodysplastic syndromes, and in β-thalassemia, a disease model of accelerating cellular aging; and (ii) describe novel therapeutic metabolic-targeted options for the aforementioned diseases, focusing on the need for continuous research in this field. Full article

Introduction: In hemoglobinopathies, the amount of globin synthesis in hemoglobin (Hb) or its structure is altered. Clinical features are related to the rate and kind of structural aberrations. The heterozygous form of the Lepore syndrome resembles minor thalassemia both clinically and hematologically. On electrophoresis, abnormal Hb Lepore fractions are found at a rate of 5–15%, with a mildly higher percentage of HbF and lower HbA. In general, Hb Lepore heterozygotes are asymptomatic. Case presentation: A 32-year-old male was admitted to our hospital with complaints of pain and swelling in multiple large joints and high-grade fever for 11 days. His past history was unremarkable; one of his sisters had the β-thalassemia trait. On physical examination, he was moderately anemic, with mild hepatomegaly and normal spleen; both knees and ankles were tender and swollen. Laboratory showed mild microcytic hypochromic anemia with variables similar to the thalassemia trait and signs of inflammation with very high CRP, serum ferritin, and leukocytosis. Blood sugars were increased. Hb electrophoresis showed an abnormal pattern with mild elevation in HbS, normal Hb F, mild reduction in HbA, and high HbA2, compatible with heterozygosity for the Hb Lepore beta chain variant. He was initially diagnosed with diabetes (treated with insulin) and sepsis from unknown origin, but fever and joint pains did not respond to NSAIDs or antibiotics. He had very good response on high-dose methylprednisolone. Undifferentiated arthritis was diagnosed in the patient with Hb Lepore, and he was treated with oral prednisolone and sulfasalazine (SSZ). At follow up, the patient was doing well. He refused further investigations and did not allow testing on his family members. In summary: Hb Lepore is a rare hemoglobinopathy linked to thalassemia, which may manifest with musculoskeletal problems. Our patient with the Hb Lepore trait presented with undifferentiated polyarthritis and fever, but in our case, a causal relationship remains unclear. This is one of the first adult cases of Hb Lepore in Bangladesh and the first with arthritis of unknown origin. The prevalence of Hb Lepore in Bangladesh is unknown. Full article

Background/Objectives: Erythrocyte alloimmunization is a critical complication impacting the efficacy of transfusion therapy in patients with thalassemia. This study seeks to evaluate the prevalence, characterization, and determinants of erythrocyte alloimmunization in multi-transfused thalassemia patients in south of Morocco. Methods: A retrospective study was conducted at the Moroccan Blood and Blood Derivatives Agency in Marrakech (Morocco) over 2 years, from June 2022 to June 2024, including 89 patients with beta-thalassemia receiving regular transfusions. The clinical, demographic, and transfusion characteristics of patients who developed alloimmunization were compared with those of non-alloimmunized patients. Results: Analysis of 89 β-thalassemia patients in the Marrakech region, mostly young and suffering from major form (67%), shows a significant male predominance (p = 0.004) and a high frequency of blood group O+ (49.4%). Alloimmunization mainly affects major forms and males and is associated with frequent annual transfusions (over 12 per year), usually resulting in the use of 24 to 60 packed red blood cell units annually. Alloimmunized patients mostly present anti-K and anti-E antibodies, indicating the involvement of the Kell and Rh systems. The direct Coombs test was more often positive in these patients (21.4% vs. 7.9%, p < 0.01). Conclusions: The high prevalence of alloimmunization in thalassemia patients in the Marrakech region highlights the need for a rigorous and personalized transfusion strategy, including molecular genotyping and alternative therapies. Full article

Background/Objectives: Thalassemias, a hereditary condition commonly linked to chronic anemia, require regular blood transfusions and repeated blood draws for assessments of hemoglobin (Hb) content, which can be uncomfortable. A promising substitute for laboratory hemoglobin testing is non-invasive spectrophotometric hemoglobin (SpHb) monitoring; however, its applicability particularly among blood transfusion-dependent thalassaemic patients needs to be investigated. This study’s primary goal was to investigate the relationships and agreements between SpHb, g/dL, and an automated hematology analyzer (Hb, g/dL) in this particular patient population. The secondary goal was to track how blood transfusions affect SpHb, g/dL, laboratory Hb, and pleth variability index (PVI, %). Methods: In this study, sixty patients were included. A Masimo Radical-7 pulse CO-oximeter was used to measure the SpHb, and a Sysmex XN-1000 hematological analyzer measured the laboratory Hb. Results: The results revealed a significant correlation between SpHb and laboratory Hb (n = 108, r = 0.587, p < 0.001) but also demonstrated that SpHb consistently overestimated laboratory Hb levels, with a mean bias of −1.18 g/dL (95% CI: −1.4344 to −0.9267). The Bland–Altman analysis showed a good degree of reliability between this bias (SpHb–Hb) and laboratory Hb (g/dL), with an Intra Class Correlation (ICC) of 0.613 but with a wide 95% CI ranging from 0.557 to 0.736 (t = 3.817, p < 0.001). The 95% limits of agreement ranged from −3.7893 to +1.4228 g/dL. Conclusions: This significant bias restricted the application of SpHb as a trustworthy method for assessing hemoglobin levels in patients with blood transfusion-dependent thalassemia. Nonetheless, the capability to monitor SpHb and PVI variations during blood transfusions offered a real-time assessment of the impact of transfusions on patients’ hemoglobin levels and volume status. Full article

Deferasirox (DFX) is an oral iron chelator for thalassemia patients with iron overload. DFX was FDA-approved as a first-line treatment for chronic iron overload. In Thailand, DFX was indicated as second-line therapy for patients unresponsive to deferiprone. Objectives: This study aimed to investigate the efficacy and safety of DFX monotherapy. Methods: All transfusion-dependent thalassemia patients who received second-line DFX monotherapy were identified from the thalassemia registry between May 2007 and May 2022. The primary endpoint was the change in body iron stores, measured by serum ferritin at week 24. At treatment end, patients with a serum ferritin (SF) level < 1000 ng/mL in transfusion-dependent thalassemia (TDT) were categorized as the ferritin response group. Multivariate analysis identified factors driving group differences. Results: Forty-two patients were enrolled with a mean age of 35.5 (13–57) years. Of these, 73.81% had beta-thalassemia. The median initial DFX dose was 20.26 (17.85–22.22) mg/kg/day, with a median treatment follow-up of 2 (1.80–2.45) years. Median SF was decreased from 2516 (1712 to 3065) ng/mL to 1027.5 (598–1867) ng/mL (p < 0.001). Of 21 (50%) patients in the ferritin response group, independent factors were age > 15 years and lower initial SF, with OR = 7.13 (95% CI 1.05–48.49, p = 0.045) and OR = 0.93 (95% CI 0.87–1.00, p = 0.039). The most common adverse events were gastric irritation symptoms (11.90%). Conclusions: Deferasirox is an effective oral iron chelator for thalassemia, with manageable side effects. Half of patients reached target SF levels. Adults (>15 years) with lower initial SF levels had a better response to DFX. Full article

Background: It has been shown that human leucocyte antigen (HLA) alleles are related to certain diseases. Some alleles were associated with alloimmunization in individuals with thalassemia. In this study, we studied the distribution of HLA alleles among beta thalassemia (BT) patients compared to healthy controls. Material and Methods: The HLA results of 100 patients with BT and 100 healthy controls were obtained for the study. The HLA-A, -B and -DRB1 tissue typing were performed at the laboratory. The low-resolution sequence-specific primer (SSP)–polymerase chain reaction (PCR-SSP) (Olerup HLA-A,B,DR typing kit, USA) and sequence-specific oligonucleotide (SSO)–PCR (LABType HLA-A,B,DR kit, ABD) methods were performed using the Luminex genotyping kits. All related data were retrospectively analyzed. Results: One in five patients (21%) underwent hematopoietic stem cell transplantation (HSCT). Patients with HSCT had significantly lower frequency of HLA-B *14, HLA-DRB1 *11 and HLA-DRB1 *16 alleles and had a higher frequency of HLA-A *66, HLA-B *41, HLA-B *55, HLA-DRB1 *3 alleles compared to patients without HSCT (p < 0.05). The HLA-A *3, HLA-B *41 and HLA-B *55 alleles were more commonly seen in HSCT patients compared to the healthy group (p = 0.04). Female patients showed a higher frequency of HLA-B *58 and HLA-DRB1 *4 alleles (p = 0.04). Conclusions: This study demonstrated that HLA-B *41 and -B *55 alleles were closely related to HSCT among BT patients. It might be considered that the variance in certain HLA-B alleles in BT patients might cause difficulty in finding a matched donor in this limited population. Full article