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 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.
Thornburg
Courtney D
CD
Duke Pediatric Sickle Cell Program and Division of Pediatric Hematology/Oncology, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA. courtney.thornburg@duke.edu
Dixon
Natalia
N
Burgett
Shelly
S
Mortier
Nicole A
NA
Schultz
William H
WH
Zimmerman
Sherri A
SA
Bonner
Melanie
M
Hardy
Kristina K
KK
Calatroni
Agustin
A
Ware
Russell E
RE
D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications*; D001827:Body Height / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002675:Child, Preschool; D002908:Chronic Disease / Q000517:prevention & control*; D003071:Cognition / Q000187:drug effects; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D010865:Pilot Projects; D011788:Quality of Life; D013154:Spleen / Q000187:drug effects / Q000502:physiology; D017585:Ultrasonography, Doppler, Transcranial
D006918:Hydroxyurea