TY - JOUR
T1 - Thalidomide confers therapeutic benefit in beta thalassemia patients by enhancing hemoglobin and hematopoietic gene expression
T2 - A non-randomized clinical trial
AU - Rahman, Inayat Ur
AU - Khan, Muhammad Tariq Masood
AU - Ali, Zahid
AU - Ahmad, Shafiq
AU - Shahid, Muhammad
AU - Zafar, Shafaq
AU - Aamir, Faheela Faizi
AU - Khan, Imran
AU - Ali, Muhammad
AU - Jelani, Musharraf
AU - Khan, Khalid
AU - Ahmad, Nafees
AU - Yousafzai, Yasar
AU - Mian, Afsar Ali
AU - Siraj, Sami
N1 - Publisher Copyright:
© 2025 Elsevier Inc.
PY - 2025/7/1
Y1 - 2025/7/1
N2 - Bacground: Transfusion-dependent β-thalassemia (TDT) requires regular transfusions, often causing iron overload and organ damage. Thalidomide, a fetal hemoglobin (HbF) inducer, may reduce transfusion needs, but scientific data are limited. Methods: This two-arm, non-randomized clinical trial followed a total of 164 TDT patients over 30 months: 72 received thalidomide and 92 underwent standard transfusions. Complete blood count was assessed at baseline and 6, 12, 18, 24, and 30 months. SNP genotyping and β-globin mutation analysis were performed using sanger sequencing. GATA-1 and KLF gene expression were assessed at baseline and after 30 months via qRT-PCR Results: Hemoglobin level in the thalidomide group significantly increased from 6.12 ± 0.65 g/dL to 8.36 ± 2.04 g/dL (p < 0.001). Among thalidomide-treated patients, 34.7 % were excellent responders (ER), 25 % good responders (GR), 13.9 % partial responders (PR), and 26.4 % non-responders (NR). ERs showed the highest GATA-1 [3.09 (IQR 2.0–3.38)] and KLF [3.24 (IQR 3.01–5.42)] expression levels (p < 0.001). Better response was observed in patients with AFT >12 months and those carrying the minor allele C at HBS1L-MYB rs9399137 (p < 0.05) Conclusion: Thalidomide effectively increases hemoglobin levels and reduces transfusion needs in TDT patients, particularly through upregulation of GATA-1 and KLF. AFT and SNP genotype at HBS1L-MYB rs9399137 may help predict response Trial registration: ClinicalTrials.gov
AB - Bacground: Transfusion-dependent β-thalassemia (TDT) requires regular transfusions, often causing iron overload and organ damage. Thalidomide, a fetal hemoglobin (HbF) inducer, may reduce transfusion needs, but scientific data are limited. Methods: This two-arm, non-randomized clinical trial followed a total of 164 TDT patients over 30 months: 72 received thalidomide and 92 underwent standard transfusions. Complete blood count was assessed at baseline and 6, 12, 18, 24, and 30 months. SNP genotyping and β-globin mutation analysis were performed using sanger sequencing. GATA-1 and KLF gene expression were assessed at baseline and after 30 months via qRT-PCR Results: Hemoglobin level in the thalidomide group significantly increased from 6.12 ± 0.65 g/dL to 8.36 ± 2.04 g/dL (p < 0.001). Among thalidomide-treated patients, 34.7 % were excellent responders (ER), 25 % good responders (GR), 13.9 % partial responders (PR), and 26.4 % non-responders (NR). ERs showed the highest GATA-1 [3.09 (IQR 2.0–3.38)] and KLF [3.24 (IQR 3.01–5.42)] expression levels (p < 0.001). Better response was observed in patients with AFT >12 months and those carrying the minor allele C at HBS1L-MYB rs9399137 (p < 0.05) Conclusion: Thalidomide effectively increases hemoglobin levels and reduces transfusion needs in TDT patients, particularly through upregulation of GATA-1 and KLF. AFT and SNP genotype at HBS1L-MYB rs9399137 may help predict response Trial registration: ClinicalTrials.gov
KW - BCL11A
KW - GATA
KW - HBS1L-MYB
KW - Thalidomide
KW - Transfusion-dependent β-thalassemia
UR - https://www.scopus.com/pages/publications/105006731016
U2 - 10.1016/j.bcmd.2025.102936
DO - 10.1016/j.bcmd.2025.102936
M3 - Article
AN - SCOPUS:105006731016
SN - 1079-9796
VL - 113-114
JO - Blood Cells, Molecules, and Diseases
JF - Blood Cells, Molecules, and Diseases
M1 - 102936
ER -