Results from the Therapeutic Response Evaluation and Adherence Trial (TREAT; Identifier: NCT02286154) published in the American Journal of Hematology indicate early use of hydroxyurea coupled with a personalized dosing strategy in children with sickle cell disease may improve clinical and laboratory response compared with traditional weight-based dosing.

Although hydroxyurea is used increasingly to treat children with sickle cell disease, pharmacokinetic (PK) profiles, treatment responses, and dosing strategies have been highly variable. Traditional weight-based dosing includes stepwise escalation until maximum tolerated dose (MTD) is reached. Though this traditional approach yields predictable laboratory and clinical results, 6 months to 1 year often elapse before results are seen.

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To establish a PK-guided starting dose, patients first received a single oral dose of 20 mg/kg hydroxyurea followed by sparse PK sampling with 3 samples collected across 3 hours. Analysis of each patient’s PK data in a population PK model resulted in starting doses directed to optimize time to MTD.

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The single center TREAT trial prospectively assessed a novel, personalized, PK-guided hydroxyurea dosing approach in 50 pediatric patients. The mean time on treatment at time of analysis was 26 months ± 15 months.

Initial hydroxyurea began at a median age of 11 months (interquartile range [IQR], 9-26). PK-guided starting dosages were 27.7 mg/kg/d ± 4.9 mg/kg/d. Median time to MTD, the primary end point, was 4.8 months (IQR, 3.3-9.3) compared with 7.8 months (IQR, 5.9-11.7)  in comparison trials (P <.0001).

Patients who began hydroxyurea with a PK-guided dose achieved a higher average fetal hemoglobin value (33.3% ± 9.1%) and hemoglobin level (10.1 g/dL ± 1.3 g/dL) compared with patients undergoing traditional dosing.

Higher PK-guided dosages did not result in additional hematologic toxicities. Furthermore, 30 patients had no treatment interruptions, while 20 had temporary hydroxyurea holds.

The authors noted that the particularly young age of this cohort precluded evaluation of this dosing strategy in older children and adolescents.


1. McGann PT, Niss O, Dong M, et al. Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia [published online May 20, 2019]. Am J Hematol. doi:10.1002/ajh.25510