Hydroxyurea for children with sickle cell disease

Abstract

Hydroxyurea therapy offers promise for ameliorating the clinical course of children with sickle cell disease (SCD). Hydroxyurea is a prototypic therapeutic option; it can be administered with minimal side effects, has a relatively wide therapeutic window, and has mechanisms of action that address pathophysiologic pathways of sickling, vaso-occlusion, hemolysis, and organ damage. There are limited data regarding hydroxyurea's ability to prevent or diminish organ dysfunction, and the long-term risks of hydroxyurea therapy remain incompletely defined. Although clinical trials are underway to address long-term issues, hydroxyurea remains an effective but underutilized therapy for SCD.

Fig. 1

Guideline for initiating, modifying, and monitoring hydroxyurea therapy (see text for further details). Asterisk indicates prehydroxyurea laboratory studies that are performed to help determine the etiology of potential treatment related laboratory changes or toxicities (eg, transaminitis, macrocytosis, and reticulocytopenia).

Fig. 2

Changes in complete blood cell count parameters and erythrocyte morphology in association with hydroxyurea therapy, from dose initiation through escalation to MTD. The initial panel shows blood counts and the peripheral blood smear at dose initiation, with hemolytic anemia and leukocytosis evident along with sickled forms. The second panel is after 8 weeks of hydroxyurea therapy (at approximately 20 mg/kg/d) with some macrocytes and anisocytosis present, along with reductions in the ANC and ARC; the dose was escalated (to approximately 25 mg/kg/d). The third panel is after 20 weeks of hydroxyurea therapy, with less anemia and sickling, more macrocytosis, and modest myelosuppression; the dose was escalated (to approximately 30 mg/kg/d). The fourth panel is after 22 months of hydroxyurea therapy (at MTD of 27 mg/kg/d); there is improved Hb with pronounced macrocytosis and no sickled forms, along with modest neutropenia and reticulocytopenia. ARC, absolute reticulocyte count; Hb, hemoglobin; HU, hydroxyurea.