SAFETY AND EFFICACY OF THALIDOMIDE IN TRANSFUSION-DEPENDENT β-THALASSEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Main Article Content

Zahid Ali
https://orcid.org/0000-0002-3795-5316
Mohammad Ismail
Muhammad Tariq Masood Khan
Inayat Ur Rehman

Abstract

OBJECTIVE: The current meta-analysis was carried out to identify the efficacy and safety of thalidomide in transfusion-dependent β-thalassemia (TDT) patients.


METHODS: Six databases: PubMed, EMBASE, Scopus, Cochrane Library, EBSCOhost, and MEDLINE were searched until November 18, 2021, for studies that assessed the efficacy of thalidomide in TDT patients by using the following search terms: “Thalidomide”, “thalidomid”, “thalomid”, “N-phthaloylglutamimide”, and Thalassemia” using Boolean or wildcard operators. Original research publications in English with observational and/or experimental designs having a sample size ≥10, regardless of age and gender, used thalidomide for ≥3 months exploring the impact of thalidomide in ameliorating transfusion needs among TDT patients were included in this meta-analysis. Data were independently extracted by two reviewers using a data extraction form. The National Institutes of Health tool was used for quality assessment.


RESULTS: Nine studies collectively involving 407 TDT patients fulfilled eligibility criteria. Thalidomide was associated with complete cessation of blood transfusion requirements with an overall response of 54% (95% CI, 34–75%) to a transfusion-independent state; heterogeneity was considered high with an I2 of 94.7%, p-value<0.001. Mild adverse events were reported in 44% of patients.


CONCLUSION: Thalidomide is a well-tolerated, effective and safe drug among TDT patients, these findings, however, should be confirmed through well-designed clinical trials.


PROSPERO Review registration number: CRD42021289950.

Article Details

How to Cite
Ali, Z., M. Ismail, M. T. M. Khan, and I. U. Rehman. “SAFETY AND EFFICACY OF THALIDOMIDE IN TRANSFUSION-DEPENDENT β-THALASSEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS”. KHYBER MEDICAL UNIVERSITY JOURNAL, vol. 14, no. 3, Sept. 2022, pp. 201-6, doi:10.35845/kmuj.2022.22729.
Section
Systematic Review & Meta-Analysis

References

Algiraigri AH, Wright NA, Paolucci EO, Kassam A. Hydroxyurea for lifelong transfusion-dependent β-thalassemia: a meta-analysis. Pediatr Hematol Oncol 2017;34(8):435-48. https://doi.org/10.1080/08880018.2017.1354948

De Sanctis V, Kattamis C, Canatan C, Soliman AT, Elsedfy H, Karimi M, et al. β-thalassemia distribution in the old world: an ancient disease seen from a historical standpoint. Mediterr J Hematol Infect Dis 2017;9(1):e2017018. https://doi.org/10.4084/mjhid.2017.018

Barnett, R. Thalassaemia. The Lancet. 2019;394(10204):1135. https://doi.org/10.1016/s0140-6736(19)32169-5

Cappellini M, Cohen A, Eleftheriou A, Piga A, Porter J, Taher A. Blood Transfusion Therapy in β-Thalassaemia Major. Chapter 2. In: Guidelines for the Clinical Management of Thalassaemia. 2nd Revised edition. Thalassaemia International Federation; 2008. Accessed on: December 06, 2021. Available from URL: https://www.ncbi.nlm.nih.gov/books/NBK173967/

Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood 2011;118(13):3479-88. https://doi.org/10.1182/blood-2010-08-300335

Vichinsky E, Neumayr L, Trimble S, Giardina PJ, Cohen AR, Coates T, et al. Transfusion complications in thalassemia patients: a report from the Centers for Disease Control and Prevention (CME). Transfusion. 2014;54(4):972-81. https://doi.org/10.1111/trf.12348

Longo F, Piolatto A, Ferrero GB, Piga A. Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs. Int J Mol Sci 2021;22(13):7229. https://doi.org/10.3390/ijms22137229

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. Front. Pharmacol. 2021;12:722502. https://doi.org/10.3389/fphar.2021.722502

Begum M, Moslem MHM, Begum NNF, Rahman MZ. Outcome of treatment with thalidomide in transfusion dependent thalassemia patients: a prospective study in a Thalassemia Center, Dhaka, Bangladesh. Am J Pediatr 2020;6(3):168-71. http://dx.doi.org/10.11648/j.ajp.20200603.11

Chandra J, Parakh N, Sidharth, Singh N, Sharma S, Goel M, et al. Efficacy and safety of thalidomide in patients with transfusion-dependent thalassemia. Indian Pediatr 2021;58(7):611-6

Yassin AK. Promising response to thalidomide in symptomatic β-thalassemia. Indian J Hematol Blood Transfus 2020;36(2):337-41. https://doi.org/10.1007/s12288-019-01231-5

Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Medicine 2009;6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097

National Institte of Health (NIH). Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group. Accessed on: December 10, 2021. Available from URL: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools

StataCorp L. StataCorp stata statistical software: Release 15. StataCorp LP.: College Station, TX, USA 2017.

Nag A, Radhakrishnan VS, Kumar J, Bhave S, Mishra DK, Nair R, et al. Thalidomide in patients with transfusion-dependent E-beta thalassemia refractory to hydroxyurea: a single-center experience. Indian J Hematol Blood Transfus. 2020;36(2):399-402. https://doi.org/10.1007/s12288-020-01263-2

Jiskani SA, Memon S. Effect of thalidomide in patients with β–thalassemia major. Hematol Transfus Int J 2018;6(6):234-6. https://doi.org/10.15406/htij.2018.06.00191

Ramanan V, Kelkar K. Role of thalidomide in treatment of beta thalassemia. J Blood Disord Med 2017;3(1):8-10. http://dx.doi.org/10.16966/2471-5026.119

Yang K, Wu Y, Zhou Y, Long B, Lu Q, Zhou T, et al. Thalidomide for patients with β-thalassemia: a multicenter experience. Mediterr J Hematol Infect Dis 2020;12(1):e2020021. https://doi.org/10.4084/mjhid.2020.021

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 β-thalassemia patients. Blood Cells Mol Dis 2020;84:102442. https://doi.org/10.1016/j.bcmd.2020.102442

Díaz-García JD, Gallegos-Villalobos A, Gonzalez-Espinoza L, Sanchez-Niño MD, Villarrubia J, Ortiz A. Deferasirox nephrotoxicity—the knowns and unknowns. Nat. Rev. Nephrol. 2014;10(10):574-86. https://doi.org/10.1038/nrneph.2014.121

Oda K, Katayama K, Tanoue A, Murata T, Hirota Y, Mizoguchi S et al. Acute kidney injury due to thin basement membrane disease mimicking Deferasirox nephrotoxicity: a case report. BMC Nephrol 2018;19(1):1-6. https://doi.org/10.1186/s12882-018-1180-2

Khan MTM. Thalidomide in Thalassemia: A Fortune in Making. Int J Pathol 2019;17(3):97-98

Delea TE, Sofrygin O, Thomas SK, Baladi JF, Phatak PD, Coates TD. Cost effectiveness of once-daily oral chelation therapy with Deferasirox versus infusional Deferoxamine in Transfusion-dependent Thalassaemia patients. Pharmacoeconomics 2007;25(4):329-42. https://doi.org/10.2165/00019053-200725040-00005

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