SAFETY AND EFFICACY OF THALIDOMIDE IN TRANSFUSION-DEPENDENT β-THALASSEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Main Article Content
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
Work published in KMUJ is licensed under a
Creative Commons Attribution 4.0 License
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
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