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Hydroxyurea (hydroxycarbamide) genotoxicity in pediatric patients with sickle cell disease
Author(s) -
Rodriguez Anar,
Duez Pierre,
Dedeken Laurence,
Cotton Frédéric,
Ferster Alina
Publication year - 2018
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.27022
Subject(s) - medicine , hydroxycarbamide , comet assay , gastroenterology , dna damage , cmax , genotoxicity , disease , nucleoid , toxicity , dna , plasma concentration , biology , genetics , escherichia coli , gene
Background Hydroxyurea (HU) reduces the severity of sickle cell disease (SCD) in children; nevertheless, its long‐term safety is an important concern. This paper evaluates HU genotoxicity at dose ≤ 30 mg/kg/day after over 2 years of treatment. Procedure The study included 76 children: 32 SCD patients treated with HU, 27 SCD patients not treated with HU, and 17 unaffected children. HU patients were classified as good or poor responders according to their clinical response. Comet assay allows the comparison of DNA damage between both groups of patients and unaffected children. Maximal concentration (C max ) of HU in plasma was determined after drug administration. Results Mean values of DNA in the comet tail were 5.13 ± 6.84 for unaffected children, 5.80 ± 7.78 for patients with SCD treated with HU, and 5.61 ± 6.91 for patients with SCD not treated with HU. Significant differences were observed between unaffected children and children with SCD. No difference was evident between comets from SCD patients treated and not treated with HU. In the case of HU, mean DNA in the comet tail was significantly lower in good responders than in poor responders: 5.54 ± 7.77 and 6.69 ± 8.43, respectively. Mean C max value on plasma was 39.08 ± 15.65 mg/l; N = 31. Conclusions SCD increases, slightly but significantly, DNA damage in lymphocytes from patients with SCD. Patients with SCD treated with HU do not present more nucleoid damage than patients with SCD not treated with HU. Good responders to the HU treatment have significantly less nucleoid damage than poor responders. HU treatment at ≤30 mg/kg/day does not expose patients to a genotoxic plasma concentration.

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