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CORRESPONDENCE Hydroxyurea (HU) has been used for more than 10 years in
children severely affected with sickle cell disease (SCD) to reduce the
number of painful episodes. Short- to medium-term tolerance of the drug
is good.1-3 Concern remains, however, about the long-term safety of the drug and, in particular, its leukemogenic potential. Leukemia has been reported in myelodysplastic syndromes after at least
3 to 4 years of exposure to the drug,4-5 so only long-term studies including significant numbers of patients can resolve concern
for SCD. So far, 3 studies on long-term effects of HU in SCD children
have been published (Table
1).6-8
Ferster et al8 refer to a malignancy observed in one SCD patient on HU, the details of which were published in an abstract reporting the European experience with HU use in SCD children.9 We believe it is important to emphasize that this leukemia occurred in a 10-year-old girl who had been treated with HU for only 7 weeks when acute lymphoblastic leukemia, with evidence of Philadelphia chromosome, was disclosed.7 It is likely that her bone pains, which were the reason for initiating HU therapy, were the first manifestations of the malignancy. Furthermore, the type of leukemia was not typical of secondary malignancy. In our opinion, this leukemia was not related to HU treatment. Thus, so far, no leukemia has been related to HU treatment in SCD children. However, a case of leukemia with background cells suggesting myelodysplasia was reported in a 27-year-old SCD patient on HU treatment for 8 years.10 Given that the number of children with long-term exposure to HU is still small, no conclusions about the long-term safety of HU in SCD can be drawn, and we think that the indications for treatment in children must remain cautious.
Mariane de Montalembert and Sally
C. Davies
References 1. Scott JP, Hillery CA, Brown ER, Misiewica V, Labotka RJ. Hydroxyurea therapy in children severely affected with sickle cell disease. J Pediatr. 1996;128:820-828[CrossRef][Medline] [Order article via Infotrieve].
2.
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 3. De Montalembert M, Belloy M, Bernaudin M, et al. Three-year follow-up of hydroxyurea treatment in severely ill children with sickle cell disease. J Pediatr Hematol Oncol. 1997;19:313-318[CrossRef][Medline] [Order article via Infotrieve].
4.
Najean Y, Rain JD, for the French Polycythemia Study Group.
Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years.
Blood.
1997;90:3370-3377
5.
Sterkers Y, Preudhomme C, Laï JL, et al.
Acute myeloid leukemia and myelodysplastic syndrome following essential thrombocytopenia treated with hydroxyurea: high proportion of cases with 17p deletion.
Blood.
1998;91:616-622
6.
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.
Blood.
1999;94:1550-1554
7.
De Montalembert M, Bégué P, Bernaudin F, Thuret I, Bachir D, Micheau M.
Preliminary report of a toxicity study of hydroxyurea in sickle cell disease.
Arch Dis Child.
1999;81:437-439
8.
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 9. Davies SC, Beuzard Y, Borgna-Pignatti C, et al. The effect of hydroxyurea in sickle cell disease: a European registry of benefits and toxicity [abstract]. Haematology. 1999;84:PO-0980. 10. Rauch A, Borromeo M, Ghafoor A, Khoyratty B, Maheshwari J. Leukemogenesis of hydroxyurea in the treatment of sickle cell anemia [abstract]. Blood. 1999;94:415a.   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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