Genotoxicity associated with hydroxyurea exposure in infants with sickle cell anemia: Results from the BABY-HUG phase III clinical trial

• Published in: Pediatric blood & cancer 2012-08, Vol.59 (2), p.254-257
• Main Authors: McGann, Patrick T., Flanagan, Jonathan M., Howard, Thad A., Dertinger, Stephen D., He, Jin, Kulharya, Anita S., Thompson, Bruce W., Ware, Russell E.
• Format: Article
• Language: English
• Subjects: Anemia, Sickle Cell - drug therapy; Anemia, Sickle Cell - genetics; Antisickling Agents - therapeutic use; DNA Damage - drug effects; DNA Damage - genetics; Double-Blind Method; Follow-Up Studies; genotoxicity; Humans; hydroxyurea; Hydroxyurea - therapeutic use; Infant; mutagenicity; Prognosis; sickle cell anemia; V(D)J Recombination
• ISSN: 1545-5009; 1545-5017; 1545-5017
• DOI: 10.1002/pbc.23365

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. Pediatr Blood Cancer 2012;59:254–257. © 2011 Wiley Periodicals, Inc.