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Muhammad Idrees
Yasar Mehmood Yousafzai
Muhammad Tariq Masood Khan
Asif Ali
Inayat Ur Rahman


Mutations, β-thalassemia, thalidomide, demographics, responders, precision medicine


Background: β-thalassemia is a significant public health problem in Pakistan with higher carrier rate and disease frequencies. Its mutation prevalence is highly geographical and ethnicity dependent.

Objective: To investigate the prevalence of genetic mutations and demographics in transfusion-dependent β-thalassemia (TDT) patients in Pakistani communities.

Methodology: Samples were gathered from TDT patients who had been diagnosed and met the inclusion criteria. The SPPS 27 was applied to analyze comprehensive patient demographics, clinical history, and prognostic data. For detection of genetic mutations in TDT patients’ DNA extraction and polymerase chain reaction (PCR) were applied using the relevant screening protocols.

Results: A total of 384 patients of TDT were screened from almost 79 various ethnic castes of Pakistan. The Cd 8-9 (+G) mutation was discovered to have the highest number of mutations followed by IVS 1-5. In demographics, Dera Ghazi Khan led in the disease prevalence, followed by Peshawar, Malakand, and Kohat divisions. The areas that have a remarkably high Excellent and Good (Ex+G) responders were Rawalpindi, Multan, Faisalabad, Gujrat, Sukkur, Shaheed Benazirabad, and Merged Districts (Fata). The areas that have comparatively poor Ex+G responders (≤50%) were Sargodha, Sahiwal, Loralai, Pasheen, and Gilgit-Baltistan.

Conclusion: Our findings determined the prevalence of genetic mutations and demographics of TDT patients in the diverse community of Pakistan with significant response to low-dose thalidomide in most of the Pakistani communities. For precision medicine and further ensuring the safety and efficacy of low-dose thalidomide in TDT patients, multicenter and large scale clinical trials with Bayesian approach are recommended.

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1. Jaing T-H, Chang T-Y, Chen S-H, Lin C-W, Wen Y-C, Chiu C-C. Molecular genetics of β-thalassemia: A narrative review. Medicine. 2021;100(45).
2. Suali L, Mohammad Salih FA, Ibrahim MY, Jeffree MSB, Thomas FM, Siew Moy F, et al. Genotype-Phenotype Study of β-Thalassemia Patients in Sabah. Hemoglobin. 2022;46(6):317-24.
3. De Simone G, Quattrocchi A, Mancini B, di Masi A, Nervi C, Ascenzi P. Thalassemias: From gene to therapy. Molecular Aspects of Medicine. 2022;84:101028.
4. Donze C, Benoit A, Thuret I, Faust C, Network N, Gauthier A, et al. β‐Thalassemia in childhood: Current state of health in a high‐income country. British Journal of Haematology. 2023.
5. Usman M, Moinuddin M, Ghani R. Molecular genetics of beta-thalassaemia syndrome in Pakistan. EMHJ-Eastern Mediterranean Health Journal, 16 (9), 972-976, 2010. 2010.
6. Ansari SH, Shamsi TS, Ashraf M, Farzana T, Bohray M, Perveen K, et al. Molecular epidemiology of β-thalassemia in Pakistan: Far reaching implications. Indian journal of human genetics. 2012;18(2):193.
7. Jalil T, Yousafzai YM, Rashid I, Ahmed S, Ali A, Fatima S, Ahmed J. Mutational analysis of Beta thalassaemia by Multiplex Arms-Pcr in Khyber Pakhtunkhwa, Pakistan. Journal of Ayub Medical College Abbottabad. 2019;31(1):98-103.
8. Mohammad SNNAi, Iberahim S, Wan Ab Rahman WS, Hassan MN, Edinur HA, Azlan M, Zulkafli Z. Single Nucleotide Polymorphisms in XMN1-HBG2, HBS1L-MYB, and BCL11A and Their Relation to High Fetal Hemoglobin Levels That Alleviate Anemia. Diagnostics. 2022;12(6):1374.
9. Kattamis A, Forni GL, Aydinok Y, Viprakasit V. Changing patterns in the epidemiology of β‐thalassemia. European Journal of Haematology. 2020;105(6):692-703.
10. Biswas B, Naskar NN, Basu K, Dasgupta A, Basu R, Paul B. Transfusion-transmitted infections, its risk factors and impact on quality of life: An epidemiological study among β-thalassemia major children. Asian Journal of Transfusion Science. 2022;16(1):99.
11. Batool T, Humayun A, Khan M, Azam MI, Khan I, Younas NS. Incidence, characteristics and laboratory parameters of epistaxis in children with β-Thalassemia major at a Tertiary Care Hospital of South Punjab, Pakistan. The Professional Medical Journal. 2023;30(04):506-10.
12. Fortina P, Dotti G, Conant R, Monokian G, Parrella T, Hitchcock W, et al. Detection of the most common mutations causing beta-thalassemia in Mediterraneans using a multiplex amplification refractory mutation system (MARMS). Genome Research. 1992;2(2):163-6.
13. Ahmed S, Anwar M. XmnI Gγ‐polymorphism in six unrelated Pakistani families with Inv/Del Gγ (Aγδβ) δβ‐thalassemia. American journal of hematology. 2005;80(4):303-5.
14. Banan M, Bayat H, Azarkeivan A, Mohammadparast S, Kamali K, Farashi S, et al. The X mn I and BCL11A single nucleotide polymorphisms may help predict hydroxyurea response in Iranian β-thalassemia patients. Hemoglobin. 2012;36(4):371-80.
15. Minaidou A, Stephanou C, Tamana S, Xenophontos M, Lederer C, Kountouris P, Kleanthous M. P128: ITHANET: AN INFORMATION AND DATABASE COMMUNITY PORTAL FOR HAEMOGLOBINOPATHIES. HemaSphere. 2022;6:31.
16. Hokland P, Daar S, Khair W, Sheth S, Taher AT, Torti L, et al. Thalassaemia—A global view. British Journal of Haematology. 2023;201(2):199-214.
17. McGann PT, Nero AC, Ware RE. Clinical features of β-thalassemia and sickle cell disease. Gene and Cell Therapies for Beta-Globinopathies. 2017:1-26.
18. Khateeb B, Moatter T, Shaghil AM, Haroon S, Kakepoto GN. Genetic diversity of beta-thalassemia mutations in Pakistani population. Journal of Pakistan Medical Association. 2000;50(9):293.
19. Yasmeen H, Toma S, Killeen N, Hasnain S, Foroni L. The molecular characterization of Beta globin gene in thalassemia patients reveals rare and a novel mutations in Pakistani population. European journal of medical genetics. 2016;59(8):355-62.
20. Shah M, Danish L, Khan NU, Zaman F, Ismail M, Hussain M, et al. Determination of mutations in iron regulating genes of beta thalassemia major patients of Khyber Pakhtunkhwa, Pakistan. Molecular Genetics & Genomic Medicine. 2020;8(9):e1310.
21. Rashid A, Tabassum S, Naeem A, Naveed A, Iqbal H, Tabassum S, Rafiq H. A rare and novel mutation in A beta-globin gene of thalassemia patient of pakistan: A case report. Annals of Medicine and Surgery. 2022;84:104918.
22. Ansari SH, Parveen S, Siddiqui S, Perveen K, Ahmed G, Kaleem B, et al. Managing thalassemia in the developing world: an evidence-based approach for prevention, transfusion independency, and curative treatment with hematopoietic stem cell transplantation. Blood advances. 2018;2(Suppl 1):42.
23. Khaliq S. Thalassemia in Pakistan. Hemoglobin. 2022;46(1):12-4.
24. Chen J, Zhu W, Cai N, Bu S, Li J, Huang L. Thalidomide induces haematologic responses in patients with β‐thalassaemia. European Journal of Haematology. 2017;99(5):437-41.
25. Kalra M, Khanna VK, Trehan A, Mahajan A. Thalidomide in transfusion dependent thalassemia: hope or hype. Journal of Pediatric Hematology/Oncology. 2017;39(6):485.
26. Li Y, Ren Q, Zhou Y, Li P, Lin W, Yin X. Thalidomide has a significant effect in patients with thalassemia intermedia. Hematology. 2018;23(1):50-4.
27. Ren Q, Zhou Y-L, Wang L, Chen Y-S, Ma Y-N, Li P-P, Yin X-L. Clinical trial on the effects of thalidomide on hemoglobin synthesis in patients with moderate thalassemia intermedia. Annals of hematology. 2018;97:1933-9.
28. Jain M, De R, Jitani A, Chakrabarti P, Mondal P, Baul S. Efficacy of thalidomide and hydroxyurea as HB F inducer in non-transfusion dependent thalassemia. Indian J Hematol Blood Transfus. 2019;35(1):S54.
29. Li X, Hu S, Liu Y, Huang J, Hong W, Xu L, et al. Efficacy of thalidomide treatment in children with transfusion dependent β-thalassemia: A retrospective clinical study. Frontiers in Pharmacology. 2021;12:722502.
30. Yang K, Wu Y, Zhou Y, Long B, Lu Q, Zhou T, et al. Thalidomide for patients with β-thalassemia: a multicenter experience. Mediterranean journal of hematology and infectious diseases. 2020;12(1).
31. Ansari SH, Ansari I, Wasim M, Sattar A, Khawaja S, Zohaib M, et al. Evaluation of the combination therapy of hydroxyurea and thalidomide in β-thalassemia. Blood Advances. 2022;6(24):6162-8.
32. Chen J-M, Zhu W-J, Liu J, Wang G-Z, Chen X-Q, Tan Y, et al. Safety and efficacy of thalidomide in patients with transfusion-dependent β-thalassemia: a randomized clinical trial. Signal Transduction and Targeted Therapy. 2021;6(1):405.
33. Dehghani Fard A, Kaviani S, Saki N, Mortaz E. Induction of fetal hemoglobin as a novel therapeutic strategy for β-hemoglobinopathy. IRCMJ.
34. Jain M, Chakrabarti P, Dolai TK, Ghosh P, Mandal PK, Baul SN, De R. Comparison of efficacy and safety of thalidomide vs hydroxyurea in patients with Hb E-β thalassemia-a pilot study from a tertiary care Centre of India. Blood Cells, Molecules, and Diseases. 2021;88:102544.
35. Kadane JB. Bayesian methods for health‐related decision making. Statistics in medicine. 2005;24(4):563-7.
36. Sheppard JW, Kaufman MA. A Bayesian approach to diagnosis and prognosis using built-in test. IEEE Transactions on Instrumentation and Measurement. 2005;54(3):1003-18.
37. Donagher J, Martin JH, Barras MA. Individualised medicine: why we need Bayesian dosing. Internal Medicine Journal. 2017;47(5):593-600.
38. Garczarek U, Muehlemann N, Richard F, Yajnik P, Russek-Cohen E. Bayesian strategies in rare diseases. Therapeutic Innovation & Regulatory Science. 2023;57(3):445-52.
39. Jahangiri M, Rahim F, Saki N, Saki Malehi A. Application of Bayesian Decision Tree in Hematology Research: Differential Diagnosis of β-Thalassemia Trait from Iron Deficiency Anemia. Computational and Mathematical Methods in Medicine. 2021;2021:1-10.
40. Muhammad Idrees, Muhammad T M Khan, Waleed Bawazir, Mohannad S. Hazzazi, Saeed M. Kabrah, Malik A. Altayar, Soad Al-Jaouni, Majed N. Almashjary, Steve Harakeh, Yasar M Yousafzai. Safety and Efficacy of Low-Dose Thalidomide in Patients with Transfusion Dependent Thalassemia: A Clinico-Hematological Assessment. Journal of Population Therapeutics and Clinical Pharmacology. 2023:30(17):1344–1353.

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