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Hydroxyurea in the treatment of major β-thalassemia and importance of genetic screening

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Abstract

Efforts have been undertaken to find an alternative approach to packed red cell transfusion (PRCT) in major β-thalassemia. Augmentation of fetal hemoglobin (HbF) by hydroxyurea (HU) has been reported to be less effective in this condition as compared to sickle cell anemia due to molecular heterogeneity of the former disease. HU efficacy and its relation to Xmn1 polymorphism and IVSII-1 mutation was evaluated in major β-thalassemics. Forty-five patients, M/F ratio 0.8, aged 6–33 years, received oral HU, 20 mg/kg per day, 4 days per week and daily1 mg folic acid. Thirty-six patients were PRCT dependent (group A) and nine independent (group B). The aim was to stabilize or increase pre-PRCT Hb over 10.0±0.5 g/dl and to reduce the need or cease the PRCT in group A and to increase Hb level and curb the ineffective erythropoesis, e.g., splenomegaly, facial bone deformity, in group B. HU was administered for at least 6 months (mean: 9 months) and discontinued in case of response failure. Screening for Xmn1 polymorphism and IVSII-1 mutation was carried out in most patients. In group A, 25 patients have become PRCT independent for a period of 2.5–7.3 years (mean: 4 years). The mean Hb, pre-HU 10.0 and post-HU 10.7 g/dl (range: 8.8–13.7 g/dl), mean serum ferritin pre- and post-HU was1877 and 525 ng/ml. The PRCT requirement was reduced in one patient, and ten patients did not respond. In group B HU has been given over 3.3 years (range: 2.8–4.8 years), Hb increased from 9.3 to 10.4/dl, and there was no tangible progression of ineffective erythropoesis. Responders in both groups expressed more comfort with this regimen. Xmn1 and IVSII-1 (homo- and/or heterozygosis) are relevant markers in most responding patients. Molecular determination of genetic markers in early childhood will help to identify candidates for pharmacological HbF switching by HU.

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References

  1. Arruda VR, Lima CS, Saad ST, Costa FF (1997)Successful use of hydroxyurea in β-thalassaemia major. N Engl J Med 336:964

    Article  CAS  Google Scholar 

  2. Blau CA, Stamatoynnopoulos G (1993) Evolving therapies in globin gene disorders. In: Lechner K, Gadner H (eds) Haematology trends ‘93 .Schattauer, New York, pp144–58

  3. Bunn HF (1999) Induction of fetal hemoglobin in sickle cell disease. Blood 9:762

    Google Scholar 

  4. Cao A, Gatanello R, Rosatelli MC (1994) Genotype-phenotype correlations in β- thalassaemia. Blood Rev 8:1–12

    CAS  PubMed  Google Scholar 

  5. Charache S (1991) Hydroxyurea as treatment for sickle cell anemia. Hematol Oncol Clin North Am 5:571–583

    CAS  PubMed  Google Scholar 

  6. Choudhry VP, Lal A, Pati HP, Arya LS (1997) Hematological responses to hydroxyurea therapy in multitransfused thalassaemic children. Indian J Pediatr 64:395–398

    CAS  PubMed  Google Scholar 

  7. Dedoussis GV, Mandilara GD, Boussiu M, Loutradis A (2000) Hb F production in beta thalassaemia heterozygotes for the IVSII-1 G➔A beta(0) globin mutation. Implication of the haplotype and the (G)gamma-158 C➔ T mutation on the Hb F level. Am J Hematol 64:151–155

    Article  CAS  PubMed  Google Scholar 

  8. Dover GJ (1998) Hemoglobin switching protocols in thalassaemia. Experience with sodium phenylbutyrate and hydroxyurea. Ann N Y Acad Sci 850:80–86

    CAS  PubMed  Google Scholar 

  9. Fucharoen S, Siritanaratkul N, Winichagoon P, Chowthaworn J, Siriboon W, Muangsup W, Chaicharoen S, Poolsup N, Chindavijak B, Pootrakul P, Piankijagum A, Schechter AN, Rogers GP (1996) Hydroxyurea increases hemoglobin F levels and improves the effectiveness of erythropoiesis in β-thalassaemia/hemoglobin E disease. Blood 87:887–892

    CAS  PubMed  Google Scholar 

  10. Hoppe C, Vichinsky E, Lewis B, Foote D, Styles L (1999) Hydroxyurea and sodium phenylbutyrate therapy in thalassaemia intermedia. Am J Hematol 62:221–227

    CAS  PubMed  Google Scholar 

  11. Huang SZ, Ren ZR, Chen MJ, Xu HP, Zeng YT, Rodgers GP, Zeng FY, Schechter AN (1994) Treatment of β-thalassaemia with hydroxyurea (HU)—effect of HU on globin gene expression. Sci China 37:1350–1359

    CAS  Google Scholar 

  12. Kinney TR, Helme RW, O’Brabski EE, Ohene-Frempong K, Wang W, Daeschner C, et al. (1999) Safety of hydroxyurea in children with sickle-cell anemia: results of the HUG-KIDS study. A phase I/II trial. Blood 94:1550–1554

    CAS  PubMed  Google Scholar 

  13. Loukopoulos D, Voskaridou E, Stamoulakatou A, Pappassotiriou Y, Kalotychou V, Loutradi A, Cozma G, Tsiarta H, Pavlides N (1998) Hydroxyurea therapy in thalassaemia. Ann N Y Acad Sci 850:120–128

    CAS  PubMed  Google Scholar 

  14. Najmabadi H, Karimi-Nejad R, Sahebjam S, Pourfarzad F, Teimourian Sh, Sahebjam F, Amirizadeh N, Karimi-Nejad MH (2001) The β-thalassaemia mutation spectrum in the Iranian population Hemoglobin 25:285–296

  15. Olivieri NF (1998) Thalassaemia: clinical management. Bailliere’s Clin Haematol 11:147–162

    CAS  Google Scholar 

  16. Olivieri NF, Rees DC, Ginder GD,Thein SL, Waye JS, Chang L, Brittenham GM, Weatherall DJ (1998) Elimination of transfusions through induction of fetal hemoglobin synthesis in Cooley’s anemia. Ann N Y Acad Sci 850:100–109

    CAS  PubMed  Google Scholar 

  17. Olivieri NF, Weatheral DJ (1998) The therapeutic reactivation of fetal haemoglobin. Hum Mol Genet 7:1655–1658

    CAS  PubMed  Google Scholar 

  18. Rachmielewitz EA, Aker M (1998) The role of recombinant human erythropoetin in the treatment of thalassaemia. Ann N Y Acad Sci 850:129–138

    CAS  PubMed  Google Scholar 

  19. Rodgers GP (1998) Pharmacological therapy. Bailliere’s Clin Haematol 11:239–255

    CAS  Google Scholar 

  20. Rodgers GP, Saunthararajah Y (2000) Advances in experimental treatment of beta-thalassaemia. Expert Opin Investig Drugs 10:925–934

    Google Scholar 

  21. Rund D, Rachmilewitz E (2000) New trends in the treatment of β-thalassaemia. Crit Rev Oncol Hematol 33:105–118

    Article  CAS  PubMed  Google Scholar 

  22. Steinberg MH, Rodgers GP (2001) Pharmacological modulation of fetal hemoglobin. Medicine 80:328–344

    Article  CAS  PubMed  Google Scholar 

  23. Vichinsky EP, Lubin BH (1994) A cautionary note regarding hydroxyurea in sickle cell disease. Blood 83:1124–1128

    CAS  PubMed  Google Scholar 

  24. Wang WC, Wyun LW, Rogers ZR, Scott JP, Lane PA, Ware RE (2001) A two year trial of hydroxyurea in very young children with sickle cell anemia. J Ped 139:790–796

    Article  CAS  Google Scholar 

  25. Zeng YT, Huang SZ, Ren ZR, Lu ZH, Zeng FY, Schechter AN, Rogers GP (1995) Hydroxyurea therapy in β-thalassaemia intermedia: improvement in haematological parameters due to enhanced beta–globin synthesis. Br J Haematol 90:557–563

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology, Shohada Medical Center, Shahid Beheshti University of Medical Sciences, Dorahe-Yousefabad, 53 Majlesi St., 15959, Tehran-Tajrish, Iran

    M. Alebouyeh, F. Moussavi, H. Haddad-Deylami & P. Vossough

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  1. M. Alebouyeh
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  2. F. Moussavi
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  3. H. Haddad-Deylami
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  4. P. Vossough
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Correspondence to M. Alebouyeh.

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Alebouyeh, M., Moussavi, F., Haddad-Deylami, H. et al. Hydroxyurea in the treatment of major β-thalassemia and importance of genetic screening. Ann Hematol 83, 430–433 (2004). https://doi.org/10.1007/s00277-003-0836-5

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  • DOI: https://doi.org/10.1007/s00277-003-0836-5

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