International Journal of Hematology

, Volume 106, Issue 6, pp 748–756 | Cite as

Hydroxyurea for hemoglobin E/β-thalassemia: a systematic review and meta-analysis

Original Article
  • 408 Downloads

Abstract

Hemoglobin E-beta thalassemia (Hb E/β-thalassemia) is a distinct, yet common, type of β-thalassemia, in which the patient co-inherits a β-thalassemia allele from one parent, and a structural variant, Hb E, from the other parent. This co-inheritance leads to remarkable clinical heterogeneity, varying degrees of chronic anemia, and a wide spectrum of complications due to ineffective erythropoiesis and iron overload. Hydroxyurea (HU), an oral chemotherapeutic drug, is expected to decrease disease severity. To assess the clinical efficacy and safety of HU in Hb E/β-thalassemia patients. We searched MEDLINE, EMBASE, Cochrane databases, and major preceding conferences for studies that assessed HU in Hb E/β-thalassemias patients. The effect size was estimated as a proportion (responder/sample size). Qualities of eligible studies were assessed using NIH tools. A total of five [one randomized clinical trial (RCT) and four observational] studies involving 106 patients were included. HU was associated with a significant RR of 46% with no statistical heterogeneity. No serious adverse effects were reported. Patients with Hb E/β-thalassemia may benefit from a trial of HU, though large RCTs assessing efficacy should be conducted to confirm the findings of this meta-analysis and to assess long-term toxicity and response sustainability.

Keywords

Hb E/β-thalassemia β-Thalassemia Hydroxyurea Meta-analysis Blood transfusion 

Notes

Acknowledgements

The authors thank the authors of the studies included in our meta-analysis for providing additional information about their studies at our request.

Author contributions

AA envisioned and designed the study, and wrote the manuscript; AK edited the protocol wrote the protocol, searched the literature, extracted the data, evaluated the quality of eligible studies, analyzed and interpreted the data, extracted the data, evaluated the quality of eligible studies, analyzed and interpreted the data and edited the manuscript.

Compliance with ethical standards

Conflict of interest

All authors state that they do not have any conflicts of interest to declare.

References

  1. 1.
    Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010;115(22):4331–6.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Olivieri NF, Pakbaz Z, Vichinsky E. Hb E/beta-thalassaemia: a common and clinically diverse disorder. Indian J Med Res. 2011;134(4):522.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Vichinsky EP. Changing patterns of thalassemia worldwide. Ann N Y Acad Sci. 2005;1054(1):18–24.CrossRefPubMedGoogle Scholar
  4. 4.
    Vichinsky E. Hemoglobin E syndromes. Hematology Am Soc Hematol Educ Program. 2007;2007:79–83. doi: 10.1182/asheducation-2007.1.79.Google Scholar
  5. 5.
    Sripichai O, Makarasara W, Munkongdee T, Kumkhaek C, Nuchprayoon I, Chuansumrit A, et al. A scoring system for the classification of β-thalassemia/Hb E disease severity. Am J Hematol. 2008;83(6):482–4.CrossRefPubMedGoogle Scholar
  6. 6.
    Weatherall DJ, Clegg JB. Historical perspectives: the many and diverse routes to our current understanding of the thalassaemias. The Thalassaemia Syndromes, 4th edn; 2001. p. 1–62.Google Scholar
  7. 7.
    Delea TE, Edelsberg J, Sofrygin O, Thomas SK, Baladi JF, Phatak PD, et al. Consequences and costs of noncompliance with iron chelation therapy in patients with transfusion-dependent thalassemia: a literature review. Transfusion. 2007;47(10):1919–29.CrossRefPubMedGoogle Scholar
  8. 8.
    Musallam KM, Taher AT, Cappellini MD, Sankaran VG. Clinical experience with fetal hemoglobin induction therapy in patients with beta-thalassemia. Blood. 2013;121(12):2199–212.CrossRefPubMedGoogle Scholar
  9. 9.
    Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA. 2000;283(15):2008–12.CrossRefPubMedGoogle Scholar
  10. 10.
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9.CrossRefPubMedGoogle Scholar
  11. 11.
    NIH. Study quality assessment tools. Available at: http://www.nhlbi.nih.gov/health-pro/guidelines/in-develop/cardiovascular-risk-reduction/tools. Accessed 10 Mar 2015.
  12. 12.
    Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Arch Public Health. 2014;72(1):39.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.CrossRefPubMedGoogle Scholar
  14. 14.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ Br Med J. 2003;327(7414):557.CrossRefGoogle Scholar
  15. 15.
    Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.CrossRefPubMedGoogle Scholar
  17. 17.
    StataCorp. 2013. Stata Statistical Software: Release 13. College Station TSL. StataCorp. 2013. Stata Statistical Software: Release 13. College Station: StataCorp LP.Google Scholar
  18. 18.
    Bohara VV, Ray S, Chakrabarti P, Ray SS, Nath UK, Chaudhuri U. Optimizing the dose of hydroxyurea therapy for patients with beta-thalassemia intermedia (Hb E-beta-thalassemia): a single center study from Eastern India. Hemoglobin. 2014;38(1):44–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Italia K, Jijina F, Merchant R, Swaminathan S, Nadkarni A, Gupta M, et al. Comparison of in vitro and in vivo response to fetal hemoglobin production and -mRNA expression by hydroxyurea in hemoglobinopathies. Indian J Hum Genet. 2013;19(2):251–8.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Italia KY, Jijina FF, Merchant R, Panjwani S, Nadkarni AH, Sawant PM, et al. Effect of hydroxyurea on the transfusion requirements in patients with severe HbE-beta-thalassaemia: a genotypic and phenotypic study. J Clin Pathol. 2010;63(2):147–50.CrossRefPubMedGoogle Scholar
  21. 21.
    Singer ST, Kuypers FA, Olivieri NF, Weatherall DJ, Mignacca R, Coates TD, Vichinsky EP. Fetal haemoglobin augmentation in E/β0 thalassaemia: clinical and haematological outcome. Br J Haematol. 2005;131(3):378–88.CrossRefPubMedGoogle Scholar
  22. 22.
    Fucharoen S, Siritanaratkul N, Winichagoon P, Chowthaworn J, Siriboon W, Muangsup W, et al. Hydroxyurea increases hemoglobin F levels and improves the effectiveness of erythropoiesis in beta-thalassemia hemoglobin E disease. Blood. 1996;87(3):887–92.PubMedGoogle Scholar
  23. 23.
    Algiraigri AH, Wright NA, Kassam A. Hydroxyurea for β-thalassemia major: a meta-analysis. Blood. 2014;124(21):4894.Google Scholar
  24. 24.
    Algiraigri AH, Radwi M. Long-term safety of hydroxyurea in sickle cell anemia and other benign diseases: systematic review and meta-analysis. Blood. 2014;124(21):560.Google Scholar
  25. 25.
    Moore RD, Charache S, Terrin ML, Barton FB, Ballas SK. Cost-effectiveness of hydroxyurea in sickle cell anemia. Investigators of the multicenter study of hydroxyurea in sickle cell anemia. Am J Hematol. 2000;64(1):26–31.CrossRefPubMedGoogle Scholar
  26. 26.
    Kavanagh BD, Fischer IBA, Segreti EM, Wheelock JB, Boardman C, Roseff SD, et al. Cost analysis of erythropoietin versus blood transfusions for cervical cancer patients receiving chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2001;51(2):435–41.CrossRefPubMedGoogle Scholar
  27. 27.
    Delea TE, Sofrygin O, Thomas SK, Baladi J-F, 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.CrossRefPubMedGoogle Scholar
  28. 28.
    Algiraigri AH, Wright NA, Paolucci EO, Kassam A. Hydroxyurea for nontransfusion-dependent β-thalassemia: a systematic review and meta-analysis. Hematol Oncol Stem Cell Ther. 2017. doi: 10.1016/j.hemonc.2017.02.002.PubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  1. 1.Department of HematologyKing Abdulaziz University HospitalJeddahSaudi Arabia
  2. 2.King Faisal Special Hospital and Research CenterJeddahSaudi Arabia
  3. 3.Department of Community Health ScienceUniversity of CalgaryCalgaryCanada

Personalised recommendations