Genotoxicity associated with hydroxyurea exposure in infants with sickle cell anemia: results from the BABY-HUG Phase III Clinical Trial

Abstract

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.

Procedure: 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.