bims-conane 2026-06-28 papers

Indian J Hematol Blood Transfus. 2026 Jul;42(4): 1282-1290

Pilot Study on the Efficacy and Safety of Thalidomide in Transfusion-Dependent and Non-transfusion-Dependent Thalassemia: A Prospective, Non-randomized Interventional Study.

Joydeb Singha, Arjin Philips Jacoby, Soumya Bhattacharya, Sudipta Sekhar Das.

Thalassemia is a heterogeneous group of inherited hemoglobin disorders broadly classified into transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). Chronic transfusion therapy in TDT often leads to complications, including iron overload and alloimmunization. Thalidomide, known for its immunomodulatory and fetal hemoglobin (HbF)-inducing properties, has shown promise in improving hematologic parameters in thalassemia. This study aimed to evaluate the efficacy and safety of thalidomide in patients with TDT and NTDT. A prospective, non-randomized study was conducted over two years at a tertiary care center in Eastern India. A total of 61 patients (25 TDT and 36 NTDT), aged 2-50 years, received thalidomide at 2-3 mg/kg/day for 24 weeks. Clinical and laboratory parameters, including hemoglobin levels, serum ferritin, HbF, organomegaly, and transfusion requirements, were assessed at baseline and post-treatment. Thalidomide therapy resulted in a significant rise in hemoglobin and HbF levels in both TDT and NTDT groups (p < 0.05). Serum ferritin levels, spleen and liver sizes, and transfusion needs were significantly reduced. By six months, 40% of TDT patients became transfusion-independent, while 80.5% of NTDT patients achieved a major hematologic response. Adverse effects were mild and included constipation, rash, and neutropenia. Thalidomide appears to be an effective and well-tolerated treatment in TDT and NTDT, offering benefits such as improved hemoglobin levels and reduced transfusion burden. Larger, randomized trials are warranted to confirm long-term safety and efficacy.

Keywords: Efficacy; Non-transfusion-dependent thalassemia; Thalassemia; Thalidomide; Transfusion-dependent thalassemia

DOI: https://doi.org/10.1007/s12288-025-02162-0

J Clin Apher. 2026 Jun;41(3): e70147

Chronic Red Cell Exchange for the Management of Alpha Thalassemia Major Complicated by Iron Overload.

Daniel Y Chang, Sanjana B Shah, Arielle Langer, Dale Davis, Sean Stowell, Suhayla Sarhan, Kristine Geary, Nelya Christiansen, Kendra Munkacsy, Roger Belizaire, Hiro Nakahara, Ryan Jajosky, David Justus, Li Chai, John Manis, Mischa Covington, Jun Liu.

Alpha thalassemia major is a severe hemoglobinopathy characterized by absent or markedly reduced alpha-globin production, necessitating lifelong blood transfusions. Chronic simple transfusions can lead to significant iron overload, often requiring iron chelation therapy. However, some patients are unable to tolerate chelation or chelation is insufficient, highlighting the need for alternative strategies for managing iron overload. This study is one of the first to evaluate the feasibility, safety, and efficacy of red blood cell exchange (RBCX) as a therapeutic option for managing iron overload while improving hemoglobin function in an alpha thalassemia major patient with iron overload despite chelation therapy. RBCX therapy was performed approximately every 3 weeks over 1 year, with frequent adjustment of exchange parameters to meet pre-transfusion target levels of functional hemoglobin. Serum ferritin levels, hemoglobin electrophoresis, and functional hemoglobin levels were tracked with each exchange transfusion. For each RBCX treatment, variant hemoglobins decreased by 3.8-fold (from 19.9% to 8.9%) and functional hemoglobin levels increased approximately 3.0 g/dL. RBCX was well tolerated and associated with a marked reduction in systemic iron burden, with serum ferritin declining 7.4-fold (86.4%) over 1 year of therapy, followed by a rise after cessation of RBCX. Cardiac iron remained within normal limits throughout the study period. In contrast, liver iron demonstrated a transient increase shortly after initiation of RBCX, but ultimately declined to levels below baseline after 1 year, even during a period in the absence of iron chelation. These findings suggest that RBCX exerts a meaningful effect on iron homeostasis and raises the possibility of a synergistic benefit when combined with iron chelation. This case highlights that RBCX is a viable therapeutic strategy to treat iron overload in patients with alpha thalassemia major.

DOI: https://doi.org/10.1002/jca.70147

J Clin Lab Anal. 2026 Jun 25. e70294

Elevated Hemoglobin A2: A Molecular Revisited, and Implications to β-Thalassemia Screening.

Kritsada Singha, Anupong Pansuwan, Hataichanok Srivorakun, Attawut Chaibunruang, Supawadee Yamsri, Wanicha Tepakhan, Kanokwan Sanchaisuriya, Goonnapa Fucharoen, Supan Fucharoen.

BACKGROUND: In Thailand, the Hb A2 cut-off value for β-thalassemia carrier has been changed from 4.0% to 3.6% since 2015. We examined the molecular basis of β-thalassemia in a large cohort of Thai subjects with this change.
METHODS: A total of 36,313 retrospective specimens encountered during January 2016 to June 2025 were reviewed, and 5909 subjects (16.7%) with Hb A2 ≥ 3.6% were recruited. Diagnosis of thalassemia was based on Hb and DNA analyses.
RESULTS: Among the 5909 subjects, 5395 (91.3%) had Hb A2A, 115 (1.9%) carried Hb variants, and the remaining 399 (6.8%) resulted from misinterpretations. Of 5395 subjects, 5117 (94.8%) carried β-thalassemia, 189 (3.5%) had normal β-globin genes, and 89 (1.6%) had incomplete molecular analysis. Fifty different β-thalassemia genes were identified, including nine hitherto undescribed in Thailand and two novel mutations, βCD81(CTC > CTA) and βIVSII-713(G > A). Falsely elevated Hb A2 was found in 364 of 399 (70.8%) subjects with misinterpretation, 20 (3.9%) represented human errors, and 15 (2.9%) resulted from Hb E blood transfusion. A low proportion of β0- and a high proportion of β+-thalassemias, a normal β-globin gene, and diagnostic errors were observed at borderline Hb A2 levels.
CONCLUSIONS: A change in the Hb A2 cut-off can alter the molecular spectrum of β-thalassemia in Thailand. The molecular basis of β-thalassemia was updated to include 50 mutations, both new and known. Misinterpretation at borderline Hb A2 should be aware and cost-effectiveness should be considered at the screening of β-thalassemia in the region.

Keywords: Hb A2 levels; diagnostic errors; molecular spectrum; β‐Thalassemia

DOI: https://doi.org/10.1002/jcla.70294

Acta Haematol. 2026 Jun 26. 1-20

Dapagliflozin in Patients with homozygous β-Thalassemia and Albuminuria.

Konstantinos Tsiotsios, Sotirios Spyridon Vamvakas, Vasiliki Labropoulou, Vasileios Lazaris, Panagiota Davoulou, Dimitra Kalavrizioti, Adamantia Bratsiakou, Themistoklis Paraskevas, Alexandra Kourakli, Dimitrios Goumenos, Evangelos Papachristou, Argiris Symeonidis, Marios Papasotiriou.

Introduction Patients with homozygous β-thalassemia show continuously improved survival, which has contributed to the development of kidney complications, predominantly expressed as increased albuminuria. In particular, patients with transfusion-dependent thalassemia (TDT), frequently develop chronic kidney complications related to chronic anemia, iron overload, and exposure to iron chelation therapy. Although sodium-glucose co-transporter 2 inhibitors (SGLT-2is) have demonstrated renoprotective effects in patients with chronic kidney disease (CKD) from other causes, their efficacy in patients with homozygous β-thalassemia and established CKD remains unknown. Methods In this prospective, open-label study we investigated the impact of dapagliflozin (10 mg/day), in patients with homozygous β-thalassemia and an albumin to creatinine ratio (ACR)>30 mg/g. Study end-points included the effect on ACR and kidney function at 6 months after treatment initiation. Furthermore, we examined the effect on systolic (SBP) and diastolic blood pressure (DBP), and on urine monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) levels. Results Twelve patients with ACR>30 mg/g received dapagliflozin and 18 patients with normal ACR were followed up for 6 months. Twenty three healthy adult individuals age- and sex-matched to the β-thalassemia group were used as normal controls. Patients with ACR>30 mg/g showed a significant reduction of ACR and SBP at 6 months (p=0.034, p=0.025 respectively) while kidney function remained stable. Patients with homozygous β-thalassemia showed increased baseline urine MCP-1 levels, while MMP-9 showed no differences versus normal controls. Those, who received dapagliflozin exhibited a significant decrease in urine MCP-1 (p=0.022) while MMP-9 remained stable. There were no significant adverse events. Conclusion Dapagliflozin at a standard dose of 10 mg daily is safe and effectively reduces albuminuria and urinary MCP-1 in patients with homozygous β-thalassemia and established CKD, suggesting potential kidney anti-inflammatory effects. Further studies with larger cohorts and longer follow-up are needed to determine its impact on CKD progression and long-term outcomes.

DOI: https://doi.org/10.1159/000552285

Cureus. 2026 May;18(5): e109539

Spectrum of Hemoglobinopathies in Microcytic Hypochromic Anemia: A Cross-Sectional Study From Western India.

Asha Goyal, Radha Sharma, Shiv Prakash Sharma, Yogesh K Gupta, Vivek Sharma.

INTRODUCTION: Hemoglobinopathies are common genetic disorders with high prevalence in India. This study aimed to determine the spectrum of hemoglobinopathies among patients with microcytic hypochromic anemia at a tertiary care center in Jaipur, Western India.
METHODS: This cross-sectional study enrolled 150 patients with microcytic hypochromic anemia (mean corpuscular volume (MCV) <80 fL, mean corpuscular hemoglobin (MCH) <27 pg) and clinically suspected hemoglobinopathy. Patients with a recent blood transfusion were excluded. Venous blood samples were analyzed using complete blood count and high-performance liquid chromatography (HPLC). Statistical analysis was performed using chi-square tests.
RESULTS: Among 150 patients, 63 (42.0%) were diagnosed with the beta-thalassemia trait, making it the most common abnormality. A normal HPLC pattern was observed in 50 (33.3%) patients. Beta-thalassemia major was diagnosed in 12 (8.0%) patients, followed by hemoglobin S (HbS) trait in seven (4.7%), hemoglobin E (HbE) homozygous in six (4.0%), hereditary persistence of fetal hemoglobin (HPFH) in four (2.7%), and other rare variants in eight (5.3%) patients. Female predominance was observed among abnormal cases (62.0% females vs. 38.0% males; female: male ratio 1.6:1; χ²=5.76, p=0.016). The highest proportion of cases was observed in the <10 years age group (30.0%), followed by the 21-30 years age group (22.0%) (χ²=28.43, p=0.005).
CONCLUSION: Beta-thalassemia trait is the predominant hemoglobinopathy in this region. High prevalence in children under 10 years and females of reproductive age underscores the need for targeted screening programs in schools and antenatal clinics.

Keywords: beta thalassemia trait; hemoglobinopathies; high-performance liquid chromatography; india; microcytic hypochromic anemia

DOI: https://doi.org/10.7759/cureus.109539