bims-conane 2025-07-27 papers

Indian J Hematol Blood Transfus. 2025 Jul;41(3): 545-550

Assessment of Serum Autophagy Related Protein Beclin-1 in Egyptian Adult Beta Thalassemia Patients.

Haydi S Mohamed, Amal M El-Afifi, Nermeen A Nabih, Esraa M Mohamed, Mostafa K El-Razzaz.

Beclin-1 has a significant role in autophagy process (Macro-autophagy). It functions through interaction with autophagy-related genes (Atgs) and other protein molecules during the process of autophagy.Here we assessed the level of serum autophagy related protein Beclin-1 in Egyptian adult beta thalassemia patients and studied its relation to ineffective erythropoiesis, transfusion requirements, iron overload.This case control study included 50 Egyptian adult beta thalassemia patients aged 18 years or more including transfusion dependent and non-transfusion dependent patients, and 25 healthy controls. The patients were selected from the Hematology Department of Ain Shams University Hospitals, Cairo, Egypt.The median (IQR) Beclin-1 level was higher in patients group in comparison to control group with highly significant statistical difference {15ng/ml (13-22) Vs 2.5ng/ml (2-3), p value < 0.001}. We found a statistically significant positive correlation between Beclin-1 level and serum ferritin (r = 0.297, p value 0.036), a negative correlation between Beclin-1 level and EF% (r=-0.379, p value 0.007), this reflects that increased Beclin-1 was associated with iron overload especially cardiac iron overload. Statistically positive correlations between Beclin-1 and liver iron concentration, transfusion/year, serum ferritin, serum iron and transferrin saturation were also found.Elevated level of Beclin-1 in adult beta Thalassemia patients correlated with cardiac and liver iron overload.

Keywords: Autophagy; Beclin-1; Iron overload; Thalassemia

DOI: https://doi.org/10.1007/s12288-024-01865-0

J Blood Med. 2025 ;16 321-330

Utilization of Fetal Hemoglobin Parameters in Predicting Clinical Severity of Sickle Cell Disease: Retrospective Study From a Tanzanian Cohort.

Hadiya M Haji, Florence Urio, Siana Nkya, Clara Chamba, Ahlam Nasser, Magdalena Lyimo, Mwashungi Ally, William Mawalla, Agnes Jonathan, Benson Kidenya, Ritah Mutagonda, Lulu Chirande, Paschal Ruggajo, Emmanuela Ambrose, Emmy Metta, Emmanuel Balandya, Julie Makani.

Background: Fetal hemoglobin (HbF) is found at a measurable amount in red blood cells (RBCs) called F cells. High fetal hemoglobin (HbF) levels are linked with milder forms of sickle cell disease (SCD). However, some patients with high HbF levels still have severe symptoms. This variability has been associated with HbF per F cell (HbF/F cell) concentration; thus, it is hypothesized that high HbF/F cell (≥10 pg) is crucial in determining SCD disease severity rather than the overall HbF and F cell levels. This study assessed the utility of these three HbF parameters as predictors of SCD clinical events in Tanzania.
Methods: A retrospective cohort study was conducted at Muhimbili University of Health and Allied Sciences, involving 92 SCD individuals aged ≥6 years, not on hydroxyurea, between September 2022 and February 2023. Data was collected from the Sickle Pan-African Research Consortium (SPARCO)-Tanzania registry. HbF/F cell was calculated as: HbF/F cell = (HbF% × MCH pg)/F cell%. STATA version 15 was used to analyze the association between HbF parameters and clinical events measured by ordinal logistic regression. A p-value <0.05 was considered statistically significant.
Results: Of the 92 SCD participants, the median age was 16 (IQR: 10-21) years, 53 (57.6%) were below 18 years, and males were 48 (52.2%). Eighty-two patients (89.1%) had HbF/F cells below 10pg. Males had significantly higher HbF/F cell levels with a median of 6.4 (IQR: 4.3-9.5) pg compared to females 5.3 (IQR: 3.5-6.5) pg (p-value = 0.004). Although, we did not observe a statistically significant association between HbF/F cell with clinical parameters, increased HbF and F cell percentages correlated with reduced odds of multiple blood transfusions by 11% (p-value = 0.016) and 3% (p-value = 0.020), respectively.
Conclusion: In this cohort, HbF and F cell levels remain important predictors of disease severity, as higher levels predicted reduced requirement for multiple blood transfusions in SCD patients, while HbF/F cells did not correlate with SCD clinical events.

Keywords: F cell; clinical parameters; disease severity; fetal hemoglobin per F cell; sickle cell

DOI: https://doi.org/10.2147/JBM.S493425

Hemoglobin. 2025 Jul 20. 1-11

Detection of Common α-Hemoglobin Variants in Thailand by Using Real-Time PCR with High Resolution Melting Analysis.

Siriphat Muangpa, Sawichayaporn Jermnim, Prissana Charoenporn, Pawanrat Suannum, Monthira Samaisombat, Peerapon Wong, Nonglak Yimtragool.

α-Hemoglobin (Hb) variants are common genetic mutations worldwide. The appropriate techniques must be followed to scan and identify these variants, particularly in routine investigations for thalassemia and hemoglobinopathies in countries with high prevalence of α and β-thalassemia. High resolution melting (HRM) analysis is a popular and effective technique for identifying genetic variations with rapid output results. This study designed four newly developed primer pairs that had full coverage of the HBA genes for detection of α-Hb variants using real-time PCR with HRM analysis. Forty-one blood samples were collected from individuals with known or suspected α-Hb variants. The results demonstrated clearly distinguished melting patterns of nine α-Hb variants including Hb Constant Spring, Hb Q-Thailand, Hb Pakse', Hb Hekinan, Hb Nakhon Ratchasima, Hb Siam, Hb Thailand, Hb Queens, and Hb Quong Sze compared with the wild-type sample pattern. All mutations were confirmed by DNA nucleotide sequencing. This study presents the first case report of the combination of Hb Shaare Zedek co-inherited with Hb Hekinan in a Thai patient. Interactions between these two Hb variants displayed a high level of Hb F (23.5%) on an HPLC Hb chromatogram and a mild symptom phenotype with low mean corpuscular volume (71.3 fL) and mean corpuscular hemoglobin (21.8 pg) in the proband. Overall, HRM analysis is a suitable, rapid, and powerful technique for the identification of gene mutations, and for the diagnosis of common and rare α-Hb variants to prevent and control thalassemia in Thailand.

Keywords: HRM analysis; Hb Shaare Zedek; real-time PCR; α-hemoglobin variants

DOI: https://doi.org/10.1080/03630269.2025.2528728

Indian J Hematol Blood Transfus. 2025 Jul;41(3): 551-557

Characterisation of β-thalassemia mutations in a tertiary care referral hospital in southern India- A descriptive study.

Dheebika Kuppusamy, Angalena Ramachandran, Nivedita Nanda, Chinnaiah Govindareddy Delhi Kumar, Rakhee Kar.

Purpose: Thalassemia is the most prevalent autosomal single-gene disorder. More than 250 mutations that impact β-globin gene expression levels through diverse mechanisms are known to cause β-thalassemia. Regional variations in β-thalassemia mutations are common. This study was undertaken to study the common β-thalassemia mutations in a tertiary care hospital in Puducherry, southern India.
Methods: The study was conducted over two years (2020-2021). Patients with β-thalassemia, their carrier parents and siblings, mainly from Puducherry and various districts of Tamil Nadu, were included to screen prevalent mutations. The genomic DNA isolated from whole blood samples was hybridized using a strip assay kit by reverse dot blot hybridization. For a few samples, DNA sequencing was done from a referral lab.
Results: Among the 92 cases, comprising 40 index cases and 52 family members, IVS I-5(G > C) was the most common mutation detected, accounting for 78%, followed by Cd 15(G > A) at 5.3% of all mutant alleles. Additional β-thalassemia mutations identified included - 28 (A > G) and Poly A site (T > C) through sequencing, along with FS Cd 41/42 (-TCTT) and Cd 8/9 (+ G) detected via strip assay. One index case of Sickle-β thalassemia with IVS I-5(G > C) + Cd 6(A > T) and another case of HbE-β thalassemia with Cd8/9(+ G) + Cd 26(G > A) mutant alleles was also identified. Uncharacterized mutant alleles in the study accounted for 4.5%.
Conclusion: This study helped us to identify the common mutation patterns in our hospital population. Additional mutations could be detected by sequencing beyond those identified through strip assay. Mutation screening plays a crucial role in genetic counselling and prenatal diagnosis.

Keywords: IVS I-5; Sequencing; Southern india; Β-thalassemia mutation; β-Globin strip assay

DOI: https://doi.org/10.1007/s12288-024-01886-9

Transplant Cell Ther. 2025 Jul 16. pii: S2666-6367(25)01323-5. [Epub ahead of print]

A ten-year follow-up study of children with thalassemia major post transplantation using treosulfan, thiotepa, and fludarabine-based conditioning regimen and its impact on growth and puberty.

Kavitha Ganesan, Vijayashree Muthukumar, Anupama Nair, Nithya Seshadri, Minakshi Balwani, Anuraag Nalla Reddy, Soundaram Valliyappan, Ramya Uppuluri, Revathi Raj.

BACKGROUND: We present a uniform cohort of children with thalassemia major who underwent treosulfan-based conditioning for hematopoietic stem cell transplantation (HSCT) and its impact on growth and puberty.
PATIENTS AND METHODS: The study included retrospective analysis of children up to 18 years of age who underwent allogeneic HSCT for transfusion-dependent thalassemia major between 2010 to 2020 with a minimum follow-up period of two years.
RESULTS: Of 202 children in the study, 59% were males and 41% were females and 110/202 (54%) had a matched family donor (MFD), 62/202 (31%) haploidentical and 30/202 (15%) matched unrelated donor (MUD). Seventy-three (36%) were <5 years of age at HSCT, 90 (45%) between 5 to 10 years, and 39 (19%) were over 10 years of age. The mean height SDS at HSCT was -0.574 and at the current assessment, the mean height SDS was -0.669 (p=0.391). There was no significant reduction in growth potential. Twenty-nine (14.4%) were short at the time of HSCT (height SDS <-2) and at the current assessment, six (20.7%) continued to remain short, while 23 (79.3%) had catch-up growth and moved to height SDS ≥-2. The mean height SDS during HSCT in Class 1 thalassemia was -0.216, -0.478 in Class 2, and -0.898 in Class 3 respectively (p=0.026). The current height SDS in these classes are -0.115, -0.710, and -0.929 respectively, confirming that children in Class 1 and 2 were able to catch up on their growth; however, Class 3 patients failed to catch up growth after HSCT (p=0.010). In the children currently above 10 years of age, 17 (43.6%) were in Tanner stage 5. Of the 83 female children, 45 (54.2%) attained spontaneous menarche. Fourteen (6.9%) children required growth hormone supplementation.
CONCLUSION: Our study demonstrates the impact of treosulfan-based conditioning on growth and puberty in children with thalassemia major. Despite the higher cost of treosulphan, growth potential was maintained and pubertal growth was per age for majority of the children in the cohort.

Keywords: GVHD; Treosulphan; growth; hematopoietic stem cell transplantation; puberty

DOI: https://doi.org/10.1016/j.jtct.2025.07.011