Is hydroxyurea leukemogenic in children with sickle cell disease?

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 (Table1).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.