A Pilot Study of Hydroxyurea to Prevent Chronic Organ Damage in Young Children With Sickle Cell Anemia

Background Hydroxyurea improves laboratory parameters and prevents acute clinical complications of sick le 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 3 5 months) received hydroxyurea at a mean maximum tolerated dose (MID) 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. I here was no significant increase in glomerular filtration rate by DTPA clearance. or Schwartz estimate. Mean transcranial Doppler(TCD) velocity changes were 25.6cm/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. Pediatr Blood Cancer 2009;52:609-615 (C) 2008 Wiley-Liss, Inc.