Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial

Abstract

Hydroxyurea (HU) enhances the synthesis of fetal hemoglobin (HbF) and can improve the clinical course of some adult patients with sickle cell anemia (SCA). In a randomized trial, we studied the biologic effects and the clinical benefit of HU in children and young adults with severe SCA. Twenty-five patients (median age, 9 years) were randomized to receive either HU (at the initial dosage of 20 mg/kg/d) or a placebo for 6 months and were then switched to the other arm for the next 6 months. Among the 22 evaluable patients (median age, 8 years), significant increases in HbF and mean corpuscular volume occurred during the HU treatment period. The white blood cell and reticulocytes counts decreased significantly, but these changes were not clinically relevant. Sixteen of 22 patients (73%) experienced a complete disappearance of events requiring hospitalization. The number of days of hospitalization as well as the number of hospitalizations for patients on HU, as compared with those for the patients receiving placebo, were significantly reduced. We conclude that treatment with HU in children and young adults is feasible, well-tolerated, and improves the clinical course of SCA. The long-term effects of HU require further investigation.

Management Of Cerebral Vasculopathy In Children With Sickle Cell Anaemia

“…There are at least three major pathophysiological bene-®cial effects of hydroxyurea in the SS patients. (i) The increase in Hb F above 15% in nearly 50% of SS subjects (Ferster et al, 1996, Steinberg et al, 1997Bunn, 1999); (ii) the modi®cation of adhesion of the Hb S reticulocyte to the vascular endothelium (Adragna et al, 1994); and (iii) myelosuppression (Charache et al, 1996;Ballas et al, 1999). Hydroxyurea therapy improves red cell deformability, decreases cellular dehydration, decreases the irreversible sickle cell fraction, modi®es red cell potassium content, improves rheology and improves RBC survival (Ballas et al, 1999).…”

“…Can hydroxyurea prevent the development of cerebral vasculopathy in the very young child? The fact that splenic germinal centres have been shown to return may be a promising model (Ferster et al, 1996;Olivieri & Vichinsky, 1998;Bernaudin, 1999). Long-term clinical trials of hydroxyurea beginning during early childhood (Jayabose et al, 1996;Scott et al, 1996;Maier-Redelsperger et al, 1998) and a multi-institutional trial in North America are in progress.…”

Hydroxyurea use in young infants with sickle cell disease

“…5 Since that time, we have seen numerous reports demonstrating the safety and efficacy of HU in both children and adults with SCD. 3,[6][7][8][9][10][11][12][13][14][15][16] There is emerging evidence to support the use of HU in infants with SCD. Starting HU in infancy, before the expected drop in hemoglobin and hemoglobin F%, could lead to even better outcomes for our patients with SCD.…”

Haemoglobin disorders in Australia: where are we now and where will we be in the future?

“…40 In the paediatric setting, there is good quality evidence that hydroxyurea reduces the frequency of painful crisis and hospitalisation. 41 However, there is an increased risk of mild and usually reversible cytopenias, rash and nail changes. Long-term data on eight children from the original hydroxyurea safety and organ toxicity study, treated with hydroxyurea for a minimum of 15 years have recently been published.…”