A pilot study of hydroxyurea to prevent chronic organ damage in young children with sickle cell anemia

Abstract

Background Hydroxyurea improves laboratory parameters and prevents acute clinical complications of sickle cell anemia (SCA) in children and adults, but its effects on organ function remain incompletely defined. Methods To assess the safety and efficacy of hydroxyurea in young children with SCA and to prospectively assess kidney and brain function, 14 young children (mean age 35 months) received hydroxyurea at a mean maximum tolerated dose (MTD) of 28 mg/kg/day. Results After a mean of 25 months, expected laboratory effects included significant increases in hemoglobin, MCV and %HbF along with significant decreases in reticulocytes, absolute neutrophil count, and bilirubin. There was no significant increase in glomerular filtration rate by DTPA clearance or Schwartz estimate. Mean transcranial Doppler (TCD) velocity changes were −25.6 cm/sec (p<0.01) and −26.8 cm/sec (p <0.05) in the right and left MCA vessels, respectively. At study exit, no child had conditional or abnormal TCD values, and none developed brain ischemic lesions or vasculopathy progression by MRI/MRA. Growth and neurocognitive scores were preserved and Impact-on-Family scores improved. Conclusions These pilot data indicate hydroxyurea at MTD is well-tolerated by both children and families, and may prevent chronic organ damage in young children with SCA.

Impact of hydroxyurea on clinical events in the BABY HUG trial

“…30 However, this may not be necessary because myelosuppression was not associated with infections or other cytopenias. Although the BABY HUG trial protocol did not include dose escalation to maximum tolerated dose, based on previously published studies [31][32][33][34] and results from the BABY HUG Follow-up Study I (NCT00890396), we expect that these subjects will tolerate dose escalation to MTD as they get older.…”

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

“…Shortly after the early phase hydroxyurea trials were completed in adults, several phase II trials established the tolerability and potential efficacy of hydroxyurea therapy in infants [52], toddlers [53], and older children [54]. The definitive benefits of hydroxyurea therapy in decreasing SCD related morbidity were replicated in children with hemoglobin SS (HbSS) or hemoglobin Sb(0)thalassaemia in a NHLBI sponsored study, the Hydroxyurea to Prevent Organ Damage in Children with Sickle Cell Anemia (BABY HUG) trial.…”

Hydroxyurea in Sickle Cell Disease: Drug Review

“…(2) Preserve splenic function in infants receiving hydroxyurea [13]. (3) Hydroxyurea has clinical efficacy for children with variable sickle-related organ damage, including proteinuria, spleen dysfunction, hypoxemia, pulmonary hypertension, glomerular hyperfiltration [18], neurocognitive delay, silent brain infarcts, elevated transcranial Doppler (TCD) velocities [18,19], primary stroke prevention [19], and secondary stroke prevention [20]. (4) In both school-age and very young patients with SCA, open label hydroxyurea has been associated with excellent growth and development [15,17].…”

“…(5) Sexual maturation, including menarche, has occurred without apparent delay [12,15]. (6) For toddlers on open-label hydroxyurea, impact-onfamily scores improved after 2 years of treatment [18]. (7) Useful to treat acute vaso-occlusive events in adults as well as children.…”