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Annals of Hematology

, Volume 93, Issue 12, pp 2045–2050 | Cite as

Response to hydroxycarbamide in pediatric β-thalassemia intermedia: 8 years’ follow-up in Egypt

  • Amal El-Beshlawy
  • Mona El-Ghamrawy
  • Mona Abou EL-Ela
  • Fadwa Said
  • Sonia Adolf
  • Abdel-Rahman Ahmed Abdel-Razek
  • Rania Ismail Magdy
  • Amina Abdel-Salam
Original Article

Abstract

Hydroxycarbamide (hydroxyurea or HU) has been shown to increase fetal hemoglobin (HbF) in patients with β-thalassemia intermedia (TI). The reported effects of HU in increasing the total hemoglobin (Hb) have been inconsistent. Studies of long-term therapy with HU in pediatric TI are rather uncommon. A retrospective observational study was carried out to evaluate the clinical responses to HU in Egyptian patients with β-TI. One hundred patients; children (n = 82, mean age 9.9 ± 4.1 years) and adults (n = 18) were studied for the mean Hb, HbF%, median serum ferritin, transfusion history, and splenic size before and after HU therapy (mean dose 20.0 ± 4.2 mg/kg/day, range 10–29 mg/kg/day) over a follow-up period 4 to 96 months (mean 35.4 ± 19.2 months). Molecular studies were also done for group of patients (n = 42). The overall response rate to HU was 79 %; 46 % were minor responders (with a reduction in transfusion rate by 50 % or more and/or an increase in their total hemoglobin level by 1–2 g/dl) and 33 % major responders (becoming transfusion-free and/or having an increase in total hemoglobin level by >2 g/dl). Mean hemoglobin increased among responders from 6.9 ± 0.9 g/dl to 8.3 ± 1.4 g/dl (p < 0.001). A significant rise in mean HbF (27.0 vs. 42.5 %; p < 0.011) and a decrease in median serum ferritin (800 vs. 644 ng/ml; p < 0.001) were also observed among responders (n = 45). Transfusions stopped in 44 % of pretreatment frequently transfused responders (n = 11/25). Splenic size decreased in 37 % of patients (n = 30/81). The predominant β-thalassemia mutation was 1–6 (T > C) in 32/42 (76 %) of studied patients; 28/32 were responders. Bivariate analysis showed no predictors of response as regards sex, pediatric and adult age, splenic status, or genotype. Hydroxycarbamide is a good therapeutic modality in the management of pediatric as in adult TI patients. It can minimize the need for blood transfusion, concomitant iron overload, and blood-born viral transmission especially in developing countries like Egypt.

Keywords

Hydroxycarbamide Hydroxyurea Thalassemia intermedia (TI) Children Egypt 

Notes

Conflict of Interest

All authors have no conflict of interest that could inappropriately influence this work.

References

  1. 1.
    Weatherall DJ, Clegg JB (2001) The thalassemia syndromes, 4th edn. Blackwell Science, Oxford, United KingdomCrossRefGoogle Scholar
  2. 2.
    Rund D, Rachmilewitz E (2005) β-thalassemia. N Engl J Med 353:1135–1146CrossRefPubMedGoogle Scholar
  3. 3.
    Najar R, Kaspar H, Shabaklo H, Makhoul N, Zalloua O (2004) Accurate and rapid prenatal diagnosis of the most frequent East Mediterranean β-thalassemia mutations. Am J Hematol 75(4):22–24Google Scholar
  4. 4.
    Thein SL (2005) Pathophysiology of ß-thalassemia—A guide to molecular therapies: Hematology; (1) 31Google Scholar
  5. 5.
    Higgs DR, Thein SL, Woods WG (2001) The molecular pathology of the thalassaemias. In: Weatherall DJ, Clegg B (eds) The thalassaemia syndromes, 4th edn. Blackwell Science, Oxford, England, pp 133–191Google Scholar
  6. 6.
    Koren A, Levin C, Dgany O, Kransnov T, Elhasid R, Zalman L, Palmor H, Tamary H (2008) Response to hydroxyurea therapy in β-thalassemia. Am J Hematol 83(5):366–370CrossRefPubMedGoogle Scholar
  7. 7.
    Zeng YT, Huang SZ, Ren ZR, Lu ZH, Zeng FY, Schechter AN, Rodgers GP (1995) Hydroxyurea therapy in beta-thalassaemia intermedia: improvement in haematological parameters due to enhanced beta-globin synthesis. Br J Hematol 90(3):557–563CrossRefGoogle Scholar
  8. 8.
    Bradai M, Abad MT, Pissard S et al (2003) Hydroxyurea can eliminate transfusion requirements in children with severe β-thalassemia. Blood 102:1529–1530CrossRefPubMedGoogle Scholar
  9. 9.
    Yavarian M, Karimi M, Bakker E et al (2004) Response to hydroxyurea treatment in Iranian transfusion-dependent b-thalassemia patients. Haematologica 89:1172–1178PubMedGoogle Scholar
  10. 10.
    Alebouyeh M, Moussavi F, Haddad-Deylami H et al (2004) Hydroxyurea in the treatment of major b-thalassemia and importance of genetic screening. Ann Haematol 83:430–433CrossRefGoogle Scholar
  11. 11.
    Camaschella C, Cappellini MD (1995) Thalassemia intermedia. Molecular basis of disease. Haematologica 80:58–68PubMedGoogle Scholar
  12. 12.
    Tan GB, Aw TC, Dunstan RA, Lee SH (1993) Evaluation of high performance liquid chromatography for routine estimation of haemoglobins A2 and F. J Clin Pathol 46(9):852–856CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Hussein IR, Temtamy SA, El-Beshlawy A, Fearon C, Shalaby Z, Vassilopoulos G, Kazazian HH (1993) Molecular characterization of β-thalassemia in Egyptians. Hum Mutat 2(1):488–452CrossRefGoogle Scholar
  14. 14.
    El-Gawhary S, El-Shafie S, Niazi M, Aziz M, El-Beshlawy A (2007) Study of beta-Thalassemia mutations using the polymerase chain reaction-amplification refractory mutation system and direct DNA sequencing techniques in a group of Egyptian Thalassemia patients. Hemoglobin 31(1):63–69CrossRefPubMedGoogle Scholar
  15. 15.
    Dixit A, Chatterjee TT, Mishra P et al (2005) Hydroxyurea in thalassemia intermedia—a promising therapy. Ann Hematol 84:441–446CrossRefPubMedGoogle Scholar
  16. 16.
    Charache S, Terrin ML, Moore RD et al (1995) Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med 332:1317–1322CrossRefPubMedGoogle Scholar
  17. 17.
    Steinberg MH, Barton F, Castro O et al (2003) Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: Risks and benefits up to 9 years of treatment. JAMA 289:1645–1651CrossRefPubMedGoogle Scholar
  18. 18.
    Loukopoulos D, Voskaridou E, Stamoulakatou A et al (1998) Hydroxyurea therapy in thalassemia. Ann N Y Acad Sci 850:120–128CrossRefPubMedGoogle Scholar
  19. 19.
    Styles L, Lewis B, Foote D et al (1998) Preliminary report: hydroxyurea produces significant clinical response in thalassemia intermedia. Ann N Y Acad Sci 850:461–462CrossRefPubMedGoogle Scholar
  20. 20.
    Hoppe C, Vichinsky E, Lewis B, Foote D, Styles L (1999) Hydroxyurea and sodium phenylbutyrate therapy in thalassemia intermedia. Am J Hematol 62:221–227CrossRefPubMedGoogle Scholar
  21. 21.
    Karimi M, Darzi H, Yavarian M (2005) Hematologic and clinical responses of thalassemia intermedia patients to hydroxyurea during 6 years of therapy in Iran. J Pediatr Hematol Oncol 27:380–385CrossRefPubMedGoogle Scholar
  22. 22.
    Ehsani MA, Hedayati-Asl AA, Bagheri A, Zeinali S, Rashidi A (2009) Hydroxyurea-induced hematological response in transfusion-independent beta thalassemia intermedia: case series and review of literature. Pediatr Hematol Oncol 26(8):560–565CrossRefPubMedGoogle Scholar
  23. 23.
    Chang YP, Littera R, Garau R et al (2001) The role of heterocellular hereditary persistence of fetal haemoglobin in β0-thalassaemia intermedia. Br J Haematol 114:899–906CrossRefPubMedGoogle Scholar
  24. 24.
    Bradai M, Pissard S, Abad MT, Dechartres A, Ribeil JA, Landais P, De Montalembert M (2007) Decreased transfusion needs with hydroxyurea therapy in Algerian patients with thalassemia major or intermedia. Transfusion 47(10):1830–1836CrossRefPubMedGoogle Scholar
  25. 25.
    Cang YC, Smith KD, Moore RD, Serjeant GR, Dover GJ (1995) An analysis of fetal haemoglobin variation in sickle cell disease: the relative contributions of the X-linked factor, b-globin haplotype, a-globin gene number, gender and age. Blood 85:1111–1117Google Scholar
  26. 26.
    Chong SS, Boehm CD, Higgs DR, Cutting GR (2000) Single tube multiplex-PCR screen for common deletional determinants of α-thalassemia. Blood 95:360–362PubMedGoogle Scholar
  27. 27.
    Higgs DR, Aldridge BE, Lamb J, Clegg JB, Weatheral DJ, Hayes RJ et al (1982) Interaction of alpha-thalassemia and homozygous sickle-cell disease. N Engl J Med 306:1441–1446CrossRefPubMedGoogle Scholar
  28. 28.
    Wang M, Tang DC, Liu W, Chin K, Zhu JG, Fibach E et al (2002) Hydroxyurea exerts bimodal dose-dependent effects on erythropoiesis in human cultured erythroid cells via distinct pathways. Br J Haematol 119:1098–1105CrossRefPubMedGoogle Scholar
  29. 29.
    Panigrahi I, Dixit A, Arora S et al (2005) Do alpha deletions influence hydroxyurea response in thalassemia intermedia? Hematology 10:61–66CrossRefPubMedGoogle Scholar
  30. 30.
    Italia KY, Jijina FJ, Merchant R et al (2009) Response to hydroxyurea in beta thalassemia major and intermedia: experience in western India. Clin Chim Acta 407(1–2):10–15CrossRefPubMedGoogle Scholar
  31. 31.
    Karimi M, Cohan N, Moosavizadeh K, Falahi MJ, Haghpanah S (2010) Adverse effects of hydroxyurea in β-thalassemia intermedia patients: 10 years’ experience. Pediatr Hematol Oncol 27(3):205–211CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Amal El-Beshlawy
    • 1
  • Mona El-Ghamrawy
    • 1
  • Mona Abou EL-Ela
    • 1
  • Fadwa Said
    • 1
  • Sonia Adolf
    • 1
  • Abdel-Rahman Ahmed Abdel-Razek
    • 1
  • Rania Ismail Magdy
    • 1
  • Amina Abdel-Salam
    • 1
  1. 1.Cairo UniversityCairoEgypt

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