Using data from the largest clinical trial to date to assess the use of hydroxyurea in pediatric patients with sickle cell anemia (SCA), researchers have provided further evidence that the therapy likely does not cause long-term genetic damage (known as genotoxicity) in young patients with SCA.
To assess whether hydroxyurea potentially causes genotoxic effects in infants with SCA, researchers analyzed patient data from the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG). This multicenter, randomized clinical trial assessed the clinical benefits of hydroxyurea in infants with SCA. Results from the study werepresented at the 53rd Annual Meeting of the American Society of Hematology in San Diego, CA.
Hydroxyurea or placebo
In this study, 193 infants between the ages of nine and 18 months were randomized to receive either hydroxyurea or placebo over the course of two years. An important secondary objective of the study was the in vivo measurement of acquired genotoxic effects of hydroxyurea, which was obtained by tracking the frequency of several laboratory-based measures of DNA damage. These markers include breaks in chromosomes or chromatids (DNA double-strands), abnormal recombination of DNA in cells of the immune system, and the formation of micronucleated reticulocytes (abnormal young red blood cells).
At the conclusion of the study, children receiving hydroxyurea did not show any significant differences in the numbers of any of the damage markers when compared with children on placebo. These data suggest that conventional doses of hydroxyurea do not appear to cause DNA damage as suggested by laboratory-based experiments that have used higher concentrations of the drug, providing reassurance that hydroxyurea presents low genotoxic risk to children.
Concerns about potential long-term genotoxic effects
?Although the clinical benefits of hydroxyurea for children with sickle cell disease are well recognized, treatment in young patients is limited due to concerns about potential long-term genotoxic effects,? said lead author Patrick T. McGann, MD, Fellow in the Department of Pediatrics in the Hematology-Oncology Section at Baylor College of Medicine in Houston. ?Results from this study contribute to a growing body of evidence suggesting that in vivo genotoxicity of hydroxyurea in sickle cell anemia appears to be low. Taken together with the clinical benefits demonstrated in the BABY HUG study, hydroxyurea may be considered as a potential therapeutic option for even very young, asymptomatic children with sickle cell anemia.?
McGann will present this study in an oral presentation
For more information:
Program: Oral and Poster Abstracts
Session: 111. Hemoglobinopathies, excluding Thalassemia: Sickle Cell Disease – Therapeutic Interventions
Abstract: 8 Genotoxicity Associated with Hydroxyurea Exposure in Infants with Sickle Cell Anemia: Results From the BABY-HUG Phase III Clinical Trial
When: Sunday, December 11, 2011: 4:30 PM
Where: Elizabeth Ballroom AB (Manchester Grand Hyatt San Diego)
– Hydroxyurea Shown to be Safe and Effective for Infants and Toddlers with Sickle Cell Anemia
– Continued Treatment of Young Childrenwith Sickle Cell Anemia with Hydroxyurea is Safe and Effective.