A Pragmatic Scoring Tool to Predict Hydroxyurea Response Among β-Thalassemia Major Patients in Pakistan

Ansari, Saqib Hussain; Hussain, Zeeshan; Zohaib, Muhammad; Parveen, Sadia; Kaleem, Bushra; Qamar, Hina; Adil, Omair; Khan, Muhammad Tahir; Shamsi, Tahir

doi:10.1097/mph.0000000000002136

Cited by 2 publications

(2 citation statements)

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“…However, 20% demonstrated a partial response and 43.75% demonstrated no response to HU. 14 This called for a search for an adjunct or alternative therapy to improve the outcomes in these patients. Thalidomide is an immune modulator that is being studied for its HbF induction potential and has demonstrated significant transfusion reduction in patients with BTM and BTI.…”

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confidence: 99%

Evaluation of the combination therapy of hydroxyurea and thalidomide in β-thalassemia

Ansari¹,

Ansari

Munir³

et al. 2022

Blood Advances

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Transfusion-related complications and lack of resources in low-to-middle-income countries have led to a search for novel therapies to reduce the need for blood transfusions in β-thalassemia patients. Hydroxyurea (HU) has demonstrated promising outcomes; additionally, thalidomide has also shown improvement in hemoglobin (Hb) levels for patients with β-thalassemia in some studies. This study presents the findings of a single-arm non-randomized trial to evaluate the efficacy of combination therapy of HU and thalidomide in children with β -thalassemia. A total of 135 patients [median age 6 (IQR 3-10) years], 77 (57%) males and 58 (43%) females were followed first using HU alone, for six months, and then using the combination of HU and thalidomide for another six months. The primary outcome was a response to therapy, as measured by the number of transfusions required and hemoglobin levels, for patients while receiving HU alone and then while using the combination therapy. Study findings showed a significant decline in blood transfusion volume (p < 0.001) and a significant increase in median Hb levels within 3 and 6 months of the combination therapy (p < 0.001). Eighty-nine (65.93%) participants were good responders, 16 (11.85%) were responders, and 30 (22.22%) were non-responders; whereas, the responders had variable genetic mutations. A total of 38 adverse events were reported which resolved on supportive treatment or temporary hold of the intervention. The combination therapy demonstrated promising results and could be considered for a diverse patient population with β-thalassemia. This trial was registered at www.clinicaltrial.gov as # NCT 05132270.

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Section: Introductionmentioning

confidence: 99%

Evaluation of the combination therapy of hydroxyurea and thalidomide in β-thalassemia

Ansari¹,

Ansari

Munir³

et al. 2022

Blood Advances

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“…In another study, specific SNPs in Xmn1 and BCL11A genes were correlated with Hydroxyurea (HU) response in Pakistani β-Thalassemia patients and found that although BCL11A polymorphisms were more prevalent in the Hydroxyurea (HU) responders, their association with HU response was not found to be statistically significant. 12 Other studies investigated Xmn1 polymorphisms in Pakistani thalassemia patients using polymerase chain reaction. [13][14][15][16] The presence of rs4671393 Polymorphisms in mentioned patients (Control, B-thalassemia, S-Bthalassemia), has been compared with their fetal hemoglobin levels by Kruskal-Wallis test.…”

Section: Discussionmentioning

confidence: 99%

Responses of β-thalassemia and compound heterozygote of Sickle/βthalassemia of BCL11A Gene Polymorphism in Pakistani Patients

Soomro,

Wahid,

Mehmood

et al. 2023

Pak J Med Sci

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Background and Objective: Beta-thalassemia major (β-Thal) and compound heterozygote of Sickle β-thalassemia (S-β Thal) are hereditary autosomal recessive disorders resulting from mutations or deletion in β-globin gene cluster. Patients with increased HbF levels having polymorphism at BCL11A site loci have shown clinical significance. The present study aimed to assess the frequency of BCL11A gene polymorphism in a study population of β-Thal, S-β Thal & Controls using Sanger sequencing leading to plot the HbF response of polymorphism with reference to wild type. Methods: The sample size of the study is n=180, groups were divided in Controls, β-thal & S-β thal. One ml blood was drawn from patients and controls to extract DNA for PCR amplification and BCL11A locus genotyping using Sanger sequencing. This study was carried out at Dow Research Institute of Biotechnology and Biomedical Sciences, for one year from March 2021 to February 2022. Results: The HbF response of three groups is hyperbolic with 83 for β-Thal, 16 for S-β Thal and close to zero for controls. The frequency of heterozygous variant GA of BCL11A gene polymorphism is 51%. The frequency of homozygous variant GG is 49%. Complete absence of wild type AA in patient group. The frequency of BCL11A polymorphism in control group was 43% (with male 18% and female 21%) showing wild type status of 57%. Conclusions: The patient groups of SCD and Beta thalassemia are devoid of wild type status. The wild type status of BCL11A is 57% even in control population. Higher level of HbF in B-thalassemia and SCD and B Thalassemia is a cost-effective screening marker before switching to an expensive genotyping testing. doi: https://doi.org/10.12669/pjms.39.6.7183 How to cite this: Soomro N, Wahid M, Mehmood M, Danish SH. Responses of β-thalassemia and compound heterozygote of Sickle/βthalassemia of BCL11A Gene Polymorphism in Pakistani Patients. Pak J Med Sci. 2023;39(6):---------. doi: https://doi.org/10.12669/pjms.39.6.7183 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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A Pragmatic Scoring Tool to Predict Hydroxyurea Response Among β-Thalassemia Major Patients in Pakistan

Cited by 2 publications

References 54 publications

Evaluation of the combination therapy of hydroxyurea and thalidomide in β-thalassemia

Evaluation of the combination therapy of hydroxyurea and thalidomide in β-thalassemia

Responses of β-thalassemia and compound heterozygote of Sickle/βthalassemia of BCL11A Gene Polymorphism in Pakistani Patients

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