Deciphering Effects of Thalidomide on Red Blood Cells in Transfusion Dependents Beta Thalassemia Patients

Summary

The goal of this Non-Randomized Clinical Trial is to determine the effects of thalidomide on red blood cells in transfusion dependent beta thalassemia patients. The main aims of this study are: * To determine the therapeutic effect of Thalidomide on hemoglobin. * To analyze association of different β- globin mutations with response to thalidomide in β-thalassemia patients. * To analyze association of Single Nucleotide Polymorphisms (SNPS) of HBG2, BCL11A and HBS1L-MYB with response to thalidomide in β-thalassemia patients. * To correlate GATA1 and KLF1 gene expression with response to thalidomide in β-thalassemia patients. Patients will be grouped into thalidomide and non-thalidomide groups on the basis of their willingness to receive thalidomide therapy. Thalidomide will be given at an average dose of 1.5mg/kg/day (range 1-2mg/kg/day). Patients will be followed up for 12 months and data will be collected at different visits. After 12 months of thalidomide therapy patients will be divided into responders and non-responders for comparative analyses on the basis of increase in hemoglobin level.

Timeline

Start

2022-01-25

Primary completion

2023-07-20

Completion

2023-10-31

Publications

• Background Ren Q, Zhou YL, Wang L, Chen YS, Ma YN, Li PP, Yin XL. Clinical trial on the effects of thalidomide on hemoglobin synthesis in patients with moderate thalassemia intermedia. Ann Hematol. 2018 Oct;97(10):1933-1939. doi: 10.1007/s00277-018-3395-5. Epub 2018 Jun 22.
• Background Aerbajinai W, Zhu J, Gao Z, Chin K, Rodgers GP. Thalidomide induces gamma-globin gene expression through increased reactive oxygen species-mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis. Blood. 2007 Oct 15;110(8):2864-71. doi: 10.1182/blood-2007-01-065201. Epub 2007 Jul 9.
• Background Yang K, Wu Y, Ma Y, Xiao J, Zhou Y, Yin X. The association of HBG2, BCL11A, and HBS1L-MYB polymorphisms to thalidomide response in Chinese beta-thalassemia patients. Blood Cells Mol Dis. 2020 Sep;84:102442. doi: 10.1016/j.bcmd.2020.102442. Epub 2020 Apr 26.
• Background Ehnert S, Linnemann C, Braun B, Botsch J, Leibiger K, Hemmann P, Nussler AAK. One-Step ARMS-PCR for the Detection of SNPs-Using the Example of the PADI4 Gene. Methods Protoc. 2019 Jul 25;2(3):63. doi: 10.3390/mps2030063.
• Background Grzasko N, Chocholska S, Goracy A, Hus M, Dmoszynska A. Thalidomide can promote erythropoiesis by induction of STAT5 and repression of external pathway of apoptosis resulting in increased expression of GATA-1 transcription factor. Pharmacol Rep. 2015 Dec;67(6):1193-200. doi: 10.1016/j.pharep.2015.05.011. Epub 2015 May 29.
• Background Martinez PA, Li R, Ramanathan HN, Bhasin M, Pearsall RS, Kumar R, Suragani RNVS. Smad2/3-pathway ligand trap luspatercept enhances erythroid differentiation in murine beta-thalassaemia by increasing GATA-1 availability. J Cell Mol Med. 2020 Jun;24(11):6162-6177. doi: 10.1111/jcmm.15243. Epub 2020 Apr 29.
• Background Jalali Far MA, Dehghani Fard A, Hajizamani S, Mossahebi-Mohammadi M, Yaghooti H, Saki N. Thalidomide is more efficient than sodium butyrate in enhancing GATA-1 and EKLF gene expression in erythroid progenitors derived from HSCs with beta-globin gene mutation. Int J Hematol Oncol Stem Cell Res. 2016 Jan 1;10(1):37-41.
• Background Guillem F, Dussiot M, Colin E, Suriyun T, Arlet JB, Goudin N, Marcion G, Seigneuric R, Causse S, Gonin P, Gastou M, Deloger M, Rossignol J, Lamarque M, Choucair ZB, Gautier EF, Ducamp S, Vandekerckhove J, Moura IC, Maciel TT, Garrido C, An X, Mayeux P, Mohandas N, Courtois G, Hermine O. XPO1 regulates erythroid differentiation and is a new target for the treatment of beta-thalassemia. Haematologica. 2020 Sep 1;105(9):2240-2249. doi: 10.3324/haematol.2018.210054.
• Background Yang K, Wu Y, Zhou Y, Long B, Lu Q, Zhou T, Wang L, Geng Z, Yin X. Thalidomide for Patients with beta-Thalassemia: A Multicenter Experience. Mediterr J Hematol Infect Dis. 2020 May 1;12(1):e2020021. doi: 10.4084/MJHID.2020.021. eCollection 2020.
• Rahman IU, Khan MTM, Ali Z, Ahmad S, Shahid M, Zafar S, Aamir FF, Khan I, Ali M, Jelani M, Khan K, Ahmad N, Yousafzai Y, Mian AA, Siraj S. Thalidomide confers therapeutic benefit in beta thalassemia patients by enhancing hemoglobin and hematopoietic gene expression: A non-randomized clinical trial. Blood Cells Mol Dis. 2025 Jul-Sep;113-114:102936. doi: 10.1016/j.bcmd.2025.102936. Epub 2025 May 23.

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