Genotoxicity associated with hydroxyurea exposure in infants with sickle cell anemia: results from the BABY-HUG Phase III Clinical Trial.
BACKGROUND
The laboratory and clinical benefits of hydroxyurea therapy for children with sickle cell anemia (SCA) are well recognized, but treatment in young patients is limited in part by concerns about long-term genotoxicity, and specifically possible carcinogenicity.


METHODS
The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) was a multicenter double-blinded placebo-controlled randomized clinical trial (NCT00006400) testing whether hydroxyurea could prevent chronic organ damage in very young patients with SCA. An important secondary objective was the measurement of acquired genotoxicity using three laboratory assays: chromosomal karyotype, illegitimate VDJ recombination events, and micronucleated reticulocyte formation.


RESULTS
Our data indicate that hydroxyurea treatment was not associated with any significant increases in genotoxicity compared to placebo treatment.


CONCLUSIONS
These data provide additional support to the safety profile of hydroxyurea for young patients with SCA, and suggest that genotoxicity in this patient population is low.
Baylor College of Medicine, Houston, Texas, USA. mcgann@bcm.edu
Patrick T
PT
McGann
Jonathan M
JM
Flanagan
Thad A
TA
Howard
Stephen D
SD
Dertinger
Jin
J
He
Anita S
AS
Kulharya
Bruce W
BW
Thompson
Russell E
RE
Ware
D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000235:genetics*; D000986:Antisickling Agents / Q000627:therapeutic use*; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics*; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D007223:Infant; D011379:Prognosis; D060152:V(D)J Recombination
D000986:Antisickling Agents; D006918:Hydroxyurea