[Hydroxyurea and other agents stimulating synthesis of fetal hemoglobin]

Five years after the initiation of the first clinical trials of hydroxyurea in pediatric sickle cell anemia patients, there is firm evidence that this drug induces a significant and sustained increase in fetal hemoglobin (HbF) production and decreases the frequency of vasoocclusive crises in the overwhelming majority of cases. The mean dosage associated with clinical benefits is 20 mg/kg/d; the HbF increase is not perfectly correlated with clinical benefits, so that a dosage increase should be considered based on the absence of a clinical improvement after three months. The daily dose should not exceed 40 g/kg. Short- and medium-term safety has been acceptable, with the few episodes of bone marrow toxicity resolving after dose attenuation or temporary drug discontinuation. Many issues remain unsettled, most notably the long-term safety of this cytostatic medication. Current knowledge gaps should be fully disclosed to parents, and hydroxyurea therapy should be reserved for patients with severe pain. Because no randomized placebo-controlled trials are available, the potential role for hydroxyurea as a preventive or curative treatment for other complications of sickle cell disease remains unknown.