Thalassemia Reports

5 pages, 301 KB

Open AccessEditor’s ChoiceCase Report

The First Gene Therapy for Treating an Indonesian Child with Thalassemia Major: A New Hope for Indonesia

by Edi Setiawan Tehuteru, Teck Onn Lim, Anky Tri Rini Kusumaning Edhy, Ludi Dhyani Rahmartani, Stephen Diah Iskandar, Cresentia Irene, Rendi Prawira Gunawan, Reganedgary Jonlean and Grace Erdiana

Thalass. Rep. 2026, 16(1), 1; https://doi.org/10.3390/thalassrep16010001 - 19 Dec 2025

Viewed by 864

Abstract

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 [...] Read more.

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

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10 pages, 222 KB

Open AccessEditor’s ChoiceArticle

Prevalence and Specificity of Red Blood Cell Alloimmunization: Insights from Transfusion-Dependent Populations in Serbia

by Radovan Dinić, Nevenka Bujandrić and Jasmina Grujić

Thalass. Rep. 2025, 15(2), 5; https://doi.org/10.3390/thalassrep15020005 - 7 May 2025

Cited by 1 | Viewed by 3436

Abstract

Background/Objectives: Red blood cell (RBC) alloimmunization is a significant challenge in transfusion medicine, particularly among transfusion-dependent patients, such as those with thalassemia. It arises from the production of antibodies against non-self RBC antigens and can lead to complications like hemolytic transfusion reactions. This [...] Read more.

Background/Objectives: Red blood cell (RBC) alloimmunization is a significant challenge in transfusion medicine, particularly among transfusion-dependent patients, such as those with thalassemia. It arises from the production of antibodies against non-self RBC antigens and can lead to complications like hemolytic transfusion reactions. This study aimed to evaluate the prevalence, specificity, and clinical implications of RBC alloimmunization at the University Clinical Center of Serbia (UCCS), emphasizing transfusion-dependent populations. Methods: This retrospective study analyzed 27,530 transfusion records at UCCS between January 2023 and January 2024. Pre-transfusion testing included ABO and RhD typing, irregular antibody screening, and crossmatching. Data from 630 patients with positive antibody screening were reviewed. Alloantibody specificity was determined using indirect antiglobulin tests and advanced phenotyping methods. Results: Among 27,530 patients, 630 (2.29%) tested positive for irregular antibodies, predominantly males (57.14%) with a mean age of 49.6 years. Alloantibodies were detected in 70.47% of cases, most commonly targeting Rh (53.35%) and Kell (17.15%) systems. Anti-E (27.93%) and anti-D (18.02%) were the most frequent antibodies. Multiple alloantibodies were identified in 18.41% of patients, posing challenges for blood compatibility. In a total of 495 patients with thalassemia, antibodies were found in 9.69%. Alloimmunization was significantly associated with higher numbers of transfusions and pregnancies (p < 0.05). Conclusions: Our findings indicate that alloimmunization is predominantly associated with Rh and Kell antigens, suggesting that implementing targeted antigen matching may reduce the frequency of alloimmunization. While our study does not directly assess the impact of genotypic matching, the prior literature supports its role in enhancing transfusion safety, particularly for high-risk populations like thalassemia patients. Full article

9 pages, 727 KB

Open AccessEditor’s ChoiceArticle

Dysregulation of Iron Homeostasis in β-Thalassemia and Impaired Neutrophil Activity

by Sreenithi Santhakumar, Leo Stephen, Aruna Barade, Uday Kulkarni, Biju George and Eunice S. Edison

Thalass. Rep. 2025, 15(2), 4; https://doi.org/10.3390/thalassrep15020004 - 25 Apr 2025

Cited by 2 | Viewed by 1817

Abstract

Background/Objective: Patients with beta-thalassemia are more susceptible to iron overload and have altered neutrophil function. This study investigated the connections between iron metabolism in neutrophils, neutrophil functionality, and overall iron status in individuals with β-thalassemia and sickle cell anemia. Methods: We recruited [...] Read more.

Background/Objective: Patients with beta-thalassemia are more susceptible to iron overload and have altered neutrophil function. This study investigated the connections between iron metabolism in neutrophils, neutrophil functionality, and overall iron status in individuals with β-thalassemia and sickle cell anemia. Methods: We recruited 18 patients with β-thalassemia, 5 patients with sickle cell anemia, and 15 healthy controls. Our evaluation included measurements of iron and hepcidin concentrations in the serum, along with an analysis of neutrophil function, specifically their phagocytic and oxidative burst capabilities. In addition, we examined the expression of iron transport proteins in neutrophils. Results: Patients with β-thalassemia showed significant iron overload, reduced neutrophil counts, and decreased oxidative burst activity and phagocytosis. Systemic iron status is inversely correlated with the phagocytic capacity of β-thalassemia neutrophils. Regression analysis indicated a significant association between serum iron level, transferrin iron binding capacity, transferrin saturation, and neutrophil percentage. These findings elucidate the essential role of systemic iron levels in neutrophil efficacy against infections. Furthermore, FPN1B and DMT1A mRNA levels were upregulated, and IRP2 was downregulated in the neutrophils of patients with β-thalassemia major and intermedia compared to controls. Conclusions: Elevated systemic iron levels were associated with reduced neutrophil counts and impaired neutrophil function in patients with β-thalassemia. These findings highlight a critical role of systemic iron overload in neutrophil dysfunction. Full article

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10 pages, 487 KB

Open AccessEditor’s ChoiceReview

New Perspectives on the Impact of Iron Chelation Therapy on the Gut Microbiome in Thalassemia Patients

by Sara Deumić, Neira Crnčević, Mirsada Hukić, Muamer Dizdar and Monia Avdić

Thalass. Rep. 2025, 15(1), 2; https://doi.org/10.3390/thalassrep15010002 - 10 Feb 2025

Cited by 1 | Viewed by 4733

Abstract

Thalassemia, a genetic condition characterized by defective hemoglobin synthesis, is often managed with transfusion therapy, which can lead to iron overload—a significant contributor to morbidity and mortality due to organ damage and pathogenic infections. Iron chelation therapy, the cornerstone of managing iron toxicity, [...] Read more.

Thalassemia, a genetic condition characterized by defective hemoglobin synthesis, is often managed with transfusion therapy, which can lead to iron overload—a significant contributor to morbidity and mortality due to organ damage and pathogenic infections. Iron chelation therapy, the cornerstone of managing iron toxicity, may inadvertently influence the gut microbiome, a critical modulator of immunity and metabolism. This review provides new insights into the interplay between iron chelation therapy and gut microbiome dynamics in thalassemia patients. It synthesizes findings on how chelators such as deferoxamine, deferasirox, and deferiprone influence microbial composition, iron availability, and systemic inflammation. Emerging evidence highlights alterations in gut microbial diversity, with reduced beneficial taxa and increased pathogenic populations, driven by changes in luminal iron levels. This imbalance contributes to immune dysregulation, systemic inflammation, and susceptibility to infections. The review advocates for tailored treatment strategies that integrate microbiome-targeted interventions alongside traditional chelation therapy to improve patient outcomes. By combining genetic profiling, dietary adjustments, and microbiome modulation, this approach offers a promising avenue for personalized medicine in thalassemia care. Full article

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11 pages, 274 KB

Open AccessEditor’s ChoiceReview

β-Thalassemia in Bangladesh: Current Status and Future Perspectives

by Arnob Mitro, Didar Hossain, Md Muhibur Rahman, Beauty Dam and Mohammad Jakir Hosen

Thalass. Rep. 2024, 14(3), 49-59; https://doi.org/10.3390/thalassrep14030007 - 8 Jul 2024

Viewed by 9331

Abstract

β-thalassemia, a life-threatening inheritable hemoglobin disorder caused by mutations in the HBB gene, poses a significant public health challenge in the world. Although no comprehensive work has been carried out in Bangladesh, the world prevalence and small-scale works indicated the possibility of a [...] Read more.

β-thalassemia, a life-threatening inheritable hemoglobin disorder caused by mutations in the HBB gene, poses a significant public health challenge in the world. Although no comprehensive work has been carried out in Bangladesh, the world prevalence and small-scale works indicated the possibility of a high prevalence of this disease in the country. Therefore, this review aims to explore the present situation of β-thalassemia in Bangladesh and propose approaches to mitigate its impact in the future. Limited awareness, a high incidence of consanguineous marriage, and inadequate access to healthcare are possible factors responsible for the high prevalence of thalassemia in Bangladesh, while the absence of public health policy and a national health insurance system further exacerbate the situation. The understanding of the genetic landscape and modern treatment strategies for β-thalassemia is hindered by the lack of comprehensive data on the mutation spectrum. In addition to conventional therapy such as blood transfusion, advanced practices such as splenectomy, hematopoietic stem cell transplantation, and emerging therapies such as gene therapy show promise for future cures but have yet to be widely implemented in this country. To effectively address the challenges of β-thalassemia, it is crucial to adopt comprehensive strategies, including a public awareness campaign, public health intervention, mandatory premarital screening, genetic counselling, and a national thalassemia prevention program. Additionally, understanding the spectrum of mutations and new therapeutic interventions is crucial for advanced healthcare strategies. Full article

11 pages, 246 KB

Open AccessEditor’s ChoiceReview

Psychological Burden among Pediatric Thalassemia Major Patients in Indonesia: A Review

by Teny Tjitra Sari, Ludi Dhyani Rahmartani, Angga Wirahmadi, Nathasha Brigitta Selene, Stephen Diah Iskandar and Pustika Amalia Wahidiyat

Thalass. Rep. 2024, 14(2), 33-43; https://doi.org/10.3390/thalassrep14020005 - 14 May 2024

Cited by 3 | Viewed by 7185

Abstract

Thalassemia a common hereditary blood disorder resulting in anemia. It is an important public health problem, with a high prevalence in Southeast Asia and Mediterranean countries, and preventable through screening programs. However, due to its chronic nature, permanent physical changes, troublesome complications, and [...] Read more.

Thalassemia a common hereditary blood disorder resulting in anemia. It is an important public health problem, with a high prevalence in Southeast Asia and Mediterranean countries, and preventable through screening programs. However, due to its chronic nature, permanent physical changes, troublesome complications, and lifelong treatment, pediatric patients with thalassemia major are more prone to mental disorders and cognitive impairment. Internalizing and externalizing problems are higher in pediatric patients with thalassemia. Children with β-thalassemia major exhibit lower IQ scores than healthy children. Neurophysiology and neuroimaging examinations have shown abnormal results in children with thalassemia. Co-morbidity with mental disorders increases the mortality, morbidity, and total healthcare costs of patients with thalassemia. Therefore, routine evaluation of mental health problems is recommended to accommodate the early detection and prompt treatment of mental disorders. A multidisciplinary approach for thalassemia patients and families should be delivered by providing appropriate medical care, psychosocial support, and good transition care to improve survival and well-being, assist good social integration and daily functioning, and cope with the stress of chronic disease. Full article

7 pages, 7614 KB

Open AccessEditor’s ChoiceCase Report

Unveiling Extramedullary Hematopoiesis: A Case Report Highlighting the Causes, Symptoms, and Management Strategies

by Konstantinos Manganas, Aikaterini Xydaki, Angeliki Kotsiafti, Olympia Papakonstantinou and Sophia Delicou

Thalass. Rep. 2024, 14(2), 26-32; https://doi.org/10.3390/thalassrep14020004 - 10 Apr 2024

Cited by 3 | Viewed by 4497

Abstract

Extramedullary hematopoiesis (EMH) serves as a compensatory mechanism in chronic hemolytic anemias, such as thalassemia, and can result in spinal cord compression. This case report highlights a 36-year-old woman with transfusion-dependent β-thalassemia (TDT) who presented with lower extremity motor deficiency, pelvic paresthesia, and [...] Read more.

Extramedullary hematopoiesis (EMH) serves as a compensatory mechanism in chronic hemolytic anemias, such as thalassemia, and can result in spinal cord compression. This case report highlights a 36-year-old woman with transfusion-dependent β-thalassemia (TDT) who presented with lower extremity motor deficiency, pelvic paresthesia, and bladder dysfunction. The patient had a history of lower back pain, bilateral lower limb weakness, and demonstrated poor compliance with iron chelation therapy. MRI findings indicated spinal cord compression attributable to extramedullary hematopoiesis. Due to the infeasibility of surgical intervention, the patient underwent hypertransfusion and iron chelation therapy. While neurological symptoms improved, urinary retention persisted. The patient continues to receive iron chelation treatment and undergo transfusions. Managing extramedullary hematopoiesis in thalassemia necessitates an individualized treatment approach. Full article

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8 pages, 1295 KB

Open AccessEditor’s ChoiceCase Report

A Case Report of Hyperhemolytic Syndrome in Sickle Cell Disease, with a Special Focus on Avoiding the Use of Transfusions

by Omar Obajed Al-Ali, György Pfliegler, Ferenc Magyari, Fanni Borics, László Imre Pinczés, Árpád Illés and Boglárka Brúgós

Thalass. Rep. 2024, 14(1), 18-25; https://doi.org/10.3390/thalassrep14010003 - 4 Mar 2024

Cited by 1 | Viewed by 5962

Abstract

In patients with sickle cell disease (SCD), transfusions pose risks like delayed hemolytic transfusion reaction (DHTR) and hyperhemolytic syndrome (HHS). We present the case of a 61-year-old Nigerian male patient with SCD, developing hyperhemolytic syndrome (HHS) post-orthopedic surgery due to alloimmunization from blood [...] Read more.

In patients with sickle cell disease (SCD), transfusions pose risks like delayed hemolytic transfusion reaction (DHTR) and hyperhemolytic syndrome (HHS). We present the case of a 61-year-old Nigerian male patient with SCD, developing hyperhemolytic syndrome (HHS) post-orthopedic surgery due to alloimmunization from blood transfusions. Surgery induced massive hemorrhage, requiring RBC transfusions. Postoperatively, he developed HHS with jaundice, hemoglobinuria, and fever. Despite additional transfusions, his condition worsened, leading to hematological consultation on postoperative day +9. Laboratory findings showed positive DAT and multiple alloantibodies. The diagnosis of HHS was established and treatment involved high-dose methylprednisolone, intravenous immunoglobulin (IVIG), and erythropoietin. The patient was discharged on postoperative day +24 with stable hemoglobin levels, tapering doses of methylprednisolone, and continuous administration of hydroxyurea prescribed. HHS pathogenesis involves extensive intravascular hemolysis, exacerbated by alloimmunization. Diagnostic challenges and therapy selection complexity underscore the need for cautious transfusion strategies in HHS, reserving them for hemodynamic instability or hypoxia. This case highlights promptly recognizing and managing HHS in SCD for improved outcomes and avoiding unnecessary transfusions. Full article

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