Trial reportBritish journal of haematology2021
Early initiation of hydroxyurea (hydroxycarbamide) using individualised, pharmacokinetics-guided dosing can produce sustained and nearly pancellular expression of fetal haemoglobin in children with sickle cell anaemia.
Trial report in British journal of haematology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02286154 (Therapeutic Response Evaluation and Adherence Trial), which is not on this map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Therapeutic Response Evaluation and Adherence Trial (TREAT): A Prospective Study of Hydroxyurea for Children With Sickle Cell Anemia
Who cites it
20 citing papers in PubMed.
- Undetectable Hydroxyurea in an Untimed Blood Sample Does Not Establish Nonadherence.American journal of hematology · 2026Article
- One cell at a time: HbF distribution in sickle cell disease.Blood advances · 2026Article
- Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations.Blood advances · 2026Article
- Optimizing the right time to start sickle cell therapies.Hematology. American Society of Hematology. Education Program · 2025Review
- Article
- Article
- The feasibility of pharmacokinetic-based dosing of hydroxyurea for children with sickle cell anaemia in Uganda: Baseline results of the alternative dosing and prevention of transfusions trial.British journal of clinical pharmacology · 2025Article
- The modern use of hydroxyurea for children with sickle cell anemia.Haematologica · 2025Review
- The feasibility of pharmacokinetic-based dosing of hydroxyurea for children with sickle cell anaemia in Uganda: Baseline results of the alternative dosing and prevention of transfusions trial.British journal of clinical pharmacology · 2025Article
- Fostering a healthier generation of children with sickle cell disease through advancements in care.Pediatric research · 2025Review
- Pharmacokinetic-Guided Hydroxyurea to Reduce Transfusions in Ugandan Children with Sickle Cell Anemia: Study Design of the Alternative Dosing And Prevention of Transfusions Trial.Acta haematologica · 2025Article
- Rationale, Development, and Validation of HdxSim, a Clinical Decision Support Tool for Model-Informed Precision Dosing of Hydroxyurea for Children with Sickle Cell Anemia.Clinical pharmacology and therapeutics · 2024Article
- Factors associated with adverse outcome among children with sickle cell disease admitted to the pediatric intensive care unit: an observational cohort.Annals of intensive care · 2024Article
- Oxygen gradient ektacytometry-derived biomarkers are associated with acute complications in sickle cell disease.Blood advances · 2024Article
- Efficacy, safety, and pharmacokinetics of a new, ready-to-use, liquid hydroxyurea in children with sickle cell anemia.Blood advances · 2023Article
- SGK1 inhibition induces fetal hemoglobin expression and delays polymerization in sickle erythroid cells.Blood advances · 2023Article
- Effectiveness of Pharmacokinetic-Guided Hydroxyurea Dose Individualization in Patients with Sickle Cell Anemia: A Mini-Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Phenotypic screening of the ReFRAME drug repurposing library to discover new drugs for treating sickle cell disease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Precision Medicine and Sickle Cell Disease.HemaSphere · 2022Review
- Clinical Utility of the Addition of Molecular Genetic Testing to Newborn Screening for Sickle Cell Anemia.Frontiers in medicine · 2021Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Hydroxyurea (hydroxycarbamide) is an effective treatment for sickle cell anaemia (SCA), but clinical responses depend primarily upon the degree of fetal haemoglobin (HbF) induction and the heterogeneity of HbF expression across erythrocytes. The number and characteristics of HbF-containing cells (F-cells) are not assessed by traditional HbF measurements. Conventional hydroxyurea dosing (e.g. fixed doses or low starting doses with stepwise escalation) produces a moderate heterocellular HbF induction, but haemolysis and clinical complications continue. Robust, pancellular HbF induction is needed to minimise or fully inhibit polymerisation of sickle haemoglobin. We treated children with hydroxyurea using an individualised, pharmacokinetics-guided regimen starting at predicted maximum tolerated dose (MTD). We observed sustained HbF induction (mean >30%) for up to 6 years, which was not dependent on genetic determinants of HbF expression. Nearly 70% of patients had ≥80% F-cells (near-pancellular), and almost half had ≥90% F-cells (pancellular). The mean HbF/F-cell content was ~12 pg. Earlier age of initiation and better medication adherence were associated with high F-cell responses. In summary, early initiation of hydroxyurea using pharmacokinetics-guided starting doses at predicted MTD can achieve sustained near-pancellular or pancellular HbF expression and should be considered an achievable goal for children with SCA treated with hydroxyurea at optimal doses. Clinical trial registration number: NCT02286154 (clinicaltrials.gov).
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