Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Sickle Cell Disease

Hydroxyurea treatment for sickle cell disease: impact on haematopoietic stem cell transplantation's outcome

Bone Marrow Transplantation volume 33, pages 799–803 (2004)Cite this article

Summary:

Since 1988, 24 children have undergone haematopoietic stem cell transplantation (HSCT) for severe sickle cell disease (SCD) in our unit, 13 being grafted after having been exposed to hydroxyurea (HU) to control SCD-related complications. Different pre-transplant conditioning regimens were given over time: Bu14/Cy200 in six patients (group 1), Bu16/Cy200/antithymocyte globulin (ATG) in five (group 2) and Bu16/Cy200/ATG with HU prior to HSCT in 13 (group 3). The aim of this study is to compare the outcome after HSCT of these groups of patients, which differ according to pre-transplant drug exposure. Overall, 20 of the 24 transplanted children had stable engraftment and have remained free of SCD-related symptoms after HSCT; 19 of them are currently alive and cured of SCD. In group 1 (HU−, ATG−), we observed one unexplainable late death, one absent engraftment, one late rejection and one mixed stable chimerism. In group 2 (HU−, ATG+), we observed the absence of engraftment in two patients and one early rejection. In group 3 (HU+, ATG+), we observed no cases of either absent engraftment, mixed stable chimerism or late rejection. In our experience, pre-transplant treatment with HU seems to be associated with a lower incidence of rejection/absent engraftment in severe SCD patients. These results need to be confirmed with a larger number of patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Platt OS, Brambilla DJ, Rosse WF et al. Mortality in sickle cell disease: life expectancy and risk factors for early death. N Engl J Med 1994; 330: 1639–1644.

    Article  CAS  PubMed  Google Scholar 

  2. Ohene-Frempong K, Weiner SJ, Sleeper LA et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 1998; 91: 288–294.

    CAS  PubMed  Google Scholar 

  3. Platt OS, Thorington BD, Brambilla DJ et al. Pain in sickle cell disease: rates and risk factors for early death. N Engl J Med 1991; 325: 11–16.

    Article  CAS  PubMed  Google Scholar 

  4. Vichinsky EP, Neumayr LD, Earles AN et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. N Engl J Med 2000; 342: 1855–1865.

    Article  CAS  PubMed  Google Scholar 

  5. Vermylen C, Fernandez-Robles E, Ninane J, Cornu G . Bone marrow transplantation in five children with sickle cell anaemia. Lancet 1988; i: 1427–1428.

    Article  Google Scholar 

  6. Bernaudin F, Vernant JP, Vilmer E et al. Results of myeloblative allogenic stem cell transplant (SCT) for severe sickle cell disease (SCD) in France. Blood 2002; 11 (Suppl. 1a): 5a (abstr. 4).

    Google Scholar 

  7. Vermylen C, Cornu G, Ferster A et al. Haematopoïetic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium. Bone Marrow Transplant 1998; 22: 1–6.

    Article  CAS  PubMed  Google Scholar 

  8. Walters MC, Storb R, Patience M et al. Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease. Blood 2000; 15: 1918–1924.

    Google Scholar 

  9. Amado RG, Schiller GJ . Nonmyeloablative approaches to the treatment of sickle hemoglobinopathies. Semin Oncol 2000; 27: 82–89.

    CAS  PubMed  Google Scholar 

  10. Fixler J, Vichinsky E, Walters MC . Stem cell transplantation for sickle cell disease: can we reduce the toxicity? Pediatr Pathol Mol Med 2001; 20: 73–86.

    Article  CAS  PubMed  Google Scholar 

  11. Iannone F, Casella JF, Fuchs EJ et al. Failure of a minimally toxic non-myeloblative regimen to establish stable donor engraftment after transplantation for sickle cell anemia and β-thalassemia. Blood 2002; 11 (Suppl. 1a): 46a (abstr. 161).

    Google Scholar 

  12. Walters MC, Nienhuis AW, Vichinsky E . Novel therapeutic approaches in sickle cell disease. Hematology 2002; 1: 10–34.

    Article  Google Scholar 

  13. Locatelli F, Rocha V, Reed W et al. Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease. Blood 2003; 15: 2137–2143.

    Article  Google Scholar 

  14. Charache S, Terrin ML, Moore RD et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med 1995; 332: 1317–1322.

    Article  CAS  PubMed  Google Scholar 

  15. Charache S, Barton FB, Moore et al. Hydroxyurea in sickle cell anemia: clinical utility of a myelosuppressive ‘switching’ agent. Medicine 1996; 75: 300–326.

    Article  CAS  PubMed  Google Scholar 

  16. De Montalambert M, Belloy M, Bernaudin F et al. Three year follow-up of hydroxyurea treatment in severely ill children with sickle cell disease. The French Study Group on Sickle Cell Disease. J Pediatr Hematol Oncol 1997; 19: 313–318.

    Article  Google Scholar 

  17. De Montalembert M, Begue P, Bernaudin F et al. Preliminary report of a toxicity study of hydroxyurea in sickle cell disease. French Study Group on Sickle Cell disease. Arch Dis Child 1999; 81: 437–439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ferster A, Vermylen C, Cornu G et al. Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial. Blood 1996; 88: 1960–1964.

    CAS  PubMed  Google Scholar 

  19. Ferster A, Tahriri P, Vermylen C et al. Five years of experience with hydroxyurea in children and young adults with sickle cell disease. Blood 2001; 97: 3628–3632.

    Article  CAS  PubMed  Google Scholar 

  20. Hoppe C, Vichinsky E, Quirolo K et al. Use of hydroxyurea in children ages 2–5 years with sickle cell disease. J Pediatr Hematol Oncol 2000; 22: 330–334.

    Article  CAS  PubMed  Google Scholar 

  21. Jayabose S, Tugal O, Sandoval C et al. Clinical and hematologic effects of hydroxyurea in children with sickle cell anemia. J Pediatr 1996; 129: 559–565.

    Article  CAS  PubMed  Google Scholar 

  22. Kinney TR, Helms RW, O'Branski EE et al. Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyrea Group. Blood 1999; 94: 1550–1554.

    CAS  PubMed  Google Scholar 

  23. Ohene-Frempong K, Smith-Whitley K . Use of hydroxyurea in children with sickle cell disease: what comes next? Semin Hematol 1997; 34 (Suppl. 3): 30–41.

    CAS  PubMed  Google Scholar 

  24. Steinberg MH, Barton F, Castro O et al. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia. JAMA 2003; 289: 1645–1651.

    Article  CAS  PubMed  Google Scholar 

  25. Van Besien K, Koshy M, Anderson-Shaw L et al. Allogeneic stem cell transplantation for sickle cell disease. A study of patients’ decisions. Blood 2001; 28: 545–549.

    CAS  Google Scholar 

  26. Walters MC, Sullivan KM, Bernaudin F et al. Neurologic complications after allogeneic marrow transplantation for sickle cell anemia. Blood 1995; 85: 879–884.

    CAS  PubMed  Google Scholar 

  27. Davies SC . Bone marrow transplant for sickle cell disease – the dilemma [review]. Blood 1993; 7: 4–9.

    Article  CAS  Google Scholar 

  28. Gaziev D, Polchi P, Lucarelli G et al. Second marrow transplants for graft failure in patients with thalassemia. Bone Marrow Transplant 1999; 24: 1299–1306.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Fonds National des Recherches Scientifiques (FNRS) no. 7.4525.98; no. 7.4503.00; no. 7.4501.02.

Author information

Authors and Affiliations

  1. Haemato-Oncology Unit, Hôpital Universitaire des Enfants – ULB, Brussels, Belgium

    C Brachet, N Azzi, C Devalck, A Gourdin, A Klein, P Q Le, M Loop, E Sariban & A Ferster

  2. Laboratory of Haematology, Hôpital Universitaire Brugmann – ULB, Brussels, Belgium

    A Demulder

  3. Laboratory of Chemistry, Hôpital Universitaire Erasme – ULB, Brussels, Belgium

    B Gulbis

Authors
  1. C Brachet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N Azzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Demulder
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Devalck
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Gourdin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B Gulbis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P Q Le
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M Loop
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. E Sariban
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. A Ferster
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Ferster.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brachet, C., Azzi, N., Demulder, A. et al. Hydroxyurea treatment for sickle cell disease: impact on haematopoietic stem cell transplantation's outcome. Bone Marrow Transplant 33, 799–803 (2004). https://doi.org/10.1038/sj.bmt.1704443

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704443

Keywords

This article is cited by

Search

Advanced search

Quick links