Evidence map›Paper›PMID 21876119›Full record

Trial reportBlood2011

Pharmacokinetics, pharmacodynamics, and pharmacogenetics of hydroxyurea treatment for children with sickle cell anemia.

Russell E Ware, Jenny M Despotovic, Nicole A Mortier, Jonathan M Flanagan, Jin He, Matthew P Smeltzer, Amy C Kimble, Banu Aygun, Song Wu, Thad Howard and 1 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 86 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 4 pooled it
4.6field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT00305175 completednot on this map

Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease

TypeobservationalSponsorSt. Jude Children's Research HospitalRan2006 to 2015Enrolled260ConditionsSickle Cell Disease
NCT02042222 early_phase1completednot on this mapstarted 2013, after this paper: background citation

Novel Dose Escalation to Predict Treatment With Hydroxyurea

TypeinterventionalSponsorBaylor College of MedicineRan2013 to 2020Enrolled70ConditionsSickle Cell DiseaseArmsHydroxyurea
3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 4 syntheses or guidelines pooled it, 166 citations in OpenAlex.

  1. Pooled it
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  4. Pooled it
  5. Trial
  6. Trial
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  10. Sickle cell disease (SCD), iNKT cells, and regadenoson infusion.Transactions of the American Clinical and Climatological Association · 2012
    Trial
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. The Coming of Age of Model-Informed Precision Therapeutics for Children.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025
    Article
  17. Article
  18. Review
  19. Article
  20. Article

26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Russell E WareInternational Hematology Center of Excellence, Department of Pediatrics, Baylor College of Medicine, Houston TX, USA. reware@bcm.edu
Jenny M Despotovic
Nicole A Mortier
Jonathan M Flanagan
Jin He
Matthew P Smeltzer
Amy C Kimble
Banu Aygun
Song Wu
Thad Howard
Alex Sparreboom
Baylor College of Medicine · USCancer Research And Biostatistics · USSt. Jude Children's Research Hospital · US

Funding

Y-Globin Gene Therapy Using In Vivo SelectionU54HL070590 · NHLBI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI PERSONS, DEREK A · 2003 to 2011
$13.8M
Hydroxyurea Pharmacokinetics and PharmacogenomicsR01HL090941 · NHLBI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI WARE, RUSSELL E · 2008 to 2011
$1.5M
NHLBI NIH HHS R01 HL090941NHLBI NIH HHS R01-HL-090941NHLBI NIH HHS U54 HL070590NHLBI NIH HHS U54-HL-070590-07
6 · The paper itself

Abstract

Hydroxyurea therapy has proven laboratory and clinical efficacies for children with sickle cell anemia (SCA). When administered at maximum tolerated dose (MTD), hydroxyurea increases fetal hemoglobin (HbF) to levels ranging from 10% to 40%. However, interpatient variability of percentage of HbF (%HbF) response is high, MTD itself is variable, and accurate predictors of hydroxyurea responses do not currently exist. HUSTLE (NCT00305175) was designed to provide first-dose pharmacokinetics (PK) data for children with SCA initiating hydroxyurea therapy, to investigate pharmacodynamics (PD) parameters, including HbF response and MTD after standardized dose escalation, and to evaluate pharmacogenetics influences on PK and PD parameters. For 87 children with first-dose PK studies, substantial interpatient variability was observed, plus a novel oral absorption phenotype (rapid or slow) that influenced serum hydroxyurea levels and total hydroxyurea exposure. PD responses in 174 subjects were robust and similar to previous cohorts; %HbF at MTD was best predicted by 5 variables, including baseline %HbF, whereas MTD was best predicted by 5 variables, including serum creatinine. Pharmacogenetics analysis showed single nucleotide polymorphisms influencing baseline %HbF, including 5 within BCL11A, but none influencing MTD %HbF or dose. Accurate prediction of hydroxyurea treatment responses for SCA remains a worthy but elusive goal.

Indexed as

PharmacogeneticsAdolescentAnemia, Sickle CellBiomarkers, PharmacologicalChildChild, PreschoolDNA Mutational AnalysisDose-Response Relationship, DrugFemaleHumansHydroxyureaMaleMaximum Tolerated DosePolymorphism, Single NucleotideBiomarkers, PharmacologicalHydroxyurea

Identifiers

PMID21876119
PMCPMC3208303
OpenAlexW2034832239

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.