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Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG)
Open accessAbstract
Background Sickle cell anaemia (SCA) is associated with significant morbidity from acute complications and organ dysfunction beginning in the first year of life. In the first multicenter randomised double-blinded trial in very young children with SCA, the impact of hydroxyurea (hydroxycarbamide) therapy on organ dysfunction, clinical complications, and laboratory findings, and its toxicity, were examined. Methods Eligible subjects had HbSS or Sβ0thalassaemia, were age 9–18 months at randomisation, and were not selected for clinical severity. Subjects received liquid hydroxyurea, 20 mg/kg/day, or placebo for two years. Primary study endpoints were splenic function (qualitative uptake on 99Tc spleen scan) and renal function (glomerular filtration rate by 99mTc-DTPA clearance). Additional evaluations included: blood counts, HbF, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every two to four weeks. Findings Ninety-six subjects received hydroxyurea and 97 placebo; 86% completed the study. Significant differences were not seen for the primary endpoints, but suggestive benefit was noted in quantitative measures of spleen function. Hydroxyurea significantly decreased pain and dactylitis with trends for decreased acute chest syndrome, hospitalisation and transfusion. Hydroxyurea increased haemoglobin and HbF and decreased WBC count. Toxicity was limited to mild-moderate neutropaenia. Interpretation Although hydroxyurea treatment did not reduce splenic and renal dysfunction assessed by primary endpoint measures, it resulted in major clinical benefit because of diminished acute complications, favorable haematologic results, and a lack of unexpected toxicities. Based on the safety and efficacy data from this trial, hydroxyurea can now be considered for all very young children with SCA.
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“In contrast, all children seem to have a robust HbF response to hydroxyurea that retards the natural age-related fall in HbF.87”
From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [87]
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Citations
Cites
Cox’s regression model for counting processes: A large sample study
Andersen, P. K., & Gill, R. D. (1982) · The Annals of Statistics · doi:10.1214/aos/1176345976 · Cited by 4,419
Mortality in sickle cell disease. Life expectancy and risk factors for early death
Platt, O. S., Brambilla, D. J., Rosse, W. F., Milner, P. F., Castro, O., Steinberg, M. H., & Klug, P. P. (1994) · New England Journal of Medicine · doi:10.1056/nejm199406093302303 · Cited by 3,320
Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia
Charache, S., Terrin, M. L., Moore, R. D., Dover, G. J., Barton, F. B., Eckert, S. V., McMahon, R. P., & Bonds, D. R. (1995) · New England Journal of Medicine · doi:10.1056/nejm199505183322001 · Cited by 2,340
Pain in Sickle Cell Disease: Rates and Risk Factors
Platt, O. S., Thorington, B. D., Brambilla, D. J., Milner, P. F., Rosse, W. F., Vichinsky, E., & Kinney, T. R. (1991) · New England Journal of Medicine · doi:10.1056/nejm199107043250103 · Cited by 1,546
Prediction of Adverse Outcomes in Children with Sickle Cell Disease
Miller, S. T., Sleeper, L. A., Pegelow, C. H., Enos, L. E., Wang, W. C., Weiner, S. J., Wethers, D. L., Smith, J., & Kinney, T. R. (2000) · New England Journal of Medicine · doi:10.1056/nejm200001133420203 · Cited by 508
Self-citationThe risks and benefits of long-term use of hydroxyurea in sickle cell anemia: a 17.5 year follow-up
Steinberg, M. H., McCarthy, W. F., Castro, O., Ballas, S. K., Armstrong, F. D., Smith, W., Ataga, K., Swerdlow, P., Kutlar, A., DeCastro, L., et al. (2010) · American Journal of Hematology · doi:10.1002/ajh.21699 · Cited by 486
Self-citationVoskaridou, E., Christoulas, D., Bilalis, A., Plata, E., Varvagiannis, K., Stamatopoulos, G., Sinopoulou, K., Balassopoulou, A., Loukopoulos, D., & Terpos, E. (2010) · Blood · doi:10.1182/blood-2009-05-221333 · Cited by 430
How I use hydroxyurea to treat young patients with sickle cell anemia
Ware, R. E. (2010) · Blood · doi:10.1182/blood-2009-04-146852 · Cited by 406
Self-citationZimmerman, S. A., Schultz, W. H., Davis, J. S., Pickens, C. V., Mortier, N. A., Howard, T. A., & Ware, R. E. (2003) · Blood · doi:10.1182/blood-2003-07-2475 · Cited by 312
Self-citationSystematic Review: Hydroxyurea for the Treatment of Adults with Sickle Cell Disease
Lanzkron, S., Strouse, J. J., Wilson, R. F., Beach, M. C., Haywood, C., Park, H., Witkop, C., Bass, E. B., & Segal, J. B. (2008) · Annals of Internal Medicine · doi:10.7326/0003-4819-148-12-200806170-00221 · Cited by 288
Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study
Hankins, J. S., Ware, R. E., Rogers, Z. R., Wynn, L. W., Lane, P. A., Scott, J. P., & Wang, W. C. (2005) · Blood · doi:10.1182/blood-2004-12-4973 · Cited by 283
Self-citationHydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial
Ferster, A., Vermylen, C., Cornu, G., Buyse, M. E., Corazza, F., Devalck, C., Fondu, P., Toppet, M., & Sariban, E. (1996) · Blood · doi:10.1182/blood.v88.6.1960.bloodjournal8861960 · Cited by 276
Brawley, O. W., Cornelius, L. J., Edwards, L. R., Gamble, V. N., Green, B. L., Inturrisi, C. E., James, A., Laraque, D., Mendez, M. D., Montoya, C., et al. (2008) · Annals of Internal Medicine · doi:10.7326/0003-4819-148-12-200806170-00220 · Cited by 269
Five years of experience with hydroxyurea in children and young adults with sickle cell disease
Ferster, A., Tahriri, P., Vermylen, C., Sturbois, G., Corazza, F., Fondu, P., Devalck, C., Dresse, M. F., Feremans, W., Hunninck, K., et al. (2001) · Blood · doi:10.1182/blood.v97.11.3628 · Cited by 218
Hydroxyurea for Sickle Cell Disease: A Systematic Review for Efficacy and Toxicity in Children
Strouse, J. J., Lanzkron, S., Beach, M. C., Haywood, C., Park, H., Witkop, C., Wilson, R. F., Bass, E. B., & Segal, J. B. (2008) · PEDIATRICS · doi:10.1542/peds.2008-0441 · Cited by 217
A two-year pilot trial of hydroxyurea in very young children with sickle-cell anemia
Wang, W. C., Wynn, L. W., Rogers, Z. R., Scott, J. P., Lane, P. A., & Ware, R. E. (2001) · The Journal of Pediatrics · doi:10.1067/mpd.2001.119590 · Cited by 178
Self-citationRenal Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial
Ware, R. E., Rees, R. C., Sarnaik, S. A., Iyer, R. V., Alvarez, O. A., Casella, J. F., Shulkin, B. L., Shalaby-Rana, E. I., Strife, C. F., Miller, J. H., et al. (2009) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2009.06.060 · Cited by 138
Self-citationAcquired DNA mutations associated with in vivo hydroxyurea exposure
Hanft, V. N., Fruchtman, S. R., Pickens, C. V., Rosse, W. F., Howard, T. A., & Ware, R. E. (2000) · Blood · doi:10.1182/blood.v95.11.3589 · Cited by 127
Self-citationRogers, Z. R., Wang, W. C., Luo, Z., Iyer, R. V., Shalaby-Rana, E. I., Dertinger, S. D., Shulkin, B. L., Miller, J. H., Files, B., Lane, P. A., et al. (2011) · Blood · doi:10.1182/blood-2010-04-278747 · Cited by 115
Self-citationPrevelance and clinical correlates of glomerulopathy in children with sickle cell disease
Wigfall, D. R., Ware, R. E., Burchinal, M., Kinney, T. R., & Foreman, J. W. (2000) · The Journal of Pediatrics · doi:10.1016/s0022-3476(00)48828-1 · Cited by 101
Self-citationEnalapril and hydroxyurea therapy for children with sickle nephropathy
Fitzhugh, C. D., Wigfall, D. R., & Ware, R. E. (2005) · Pediatric Blood & Cancer · doi:10.1002/pbc.20296 · Cited by 99
Self-citationHankins, J. S., Helton, K. J., McCarville, M. B., Li, C., Wang, W. C., & Ware, R. E. (2007) · Pediatric Blood & Cancer · doi:10.1002/pbc.21271 · Cited by 98
Self-citationThornburg, C. D., Dixon, N., Burgett, S. E., Mortier, N. A., Schultz, W. H., Zimmerman, S. A., Bonner, M. J., Hardy, K. K., Calatroni, A., & Ware, R. E. (2008) · Pediatric Blood & Cancer · doi:10.1002/pbc.21738 · Cited by 96
Self-citationQuinn, C. T., Lee, N. J., Shull, E. P., Ahmad, N., Rogers, Z. R., & Buchanan, G. R. (2007) · Blood · doi:10.1182/blood-2007-07-100719 · Cited by 90
Self-citationPrevalence and clinical correlates of glomerulopathy in children with sickle cell disease
Wigfall, D. R., Ware, R. E., Burchinal, M., Kinney, T. R., & Foreman, J. W. (2000) · The Journal of Pediatrics · doi:10.1067/mpd.2000.105998 · Cited by 80
Self-citationHydroxyurea in Children with Sickle Cell Disease
Olivieri, N. F., & Vichinsky, E. P. (1998) · Journal of Pediatric Hematology/Oncology · doi:10.1097/00043426-199801000-00004 · Cited by 70
Assessment of genotoxicity associated with hydroxyurea therapy in children with sickle cell anemia
Flanagan, J. M., Howard, T. A., Mortier, N. A., Avlasevich, S. L., Smeltzer, M. P., Wu, S., Dertinger, S. D., & Ware, R. E. (2010) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2010.03.001 · Cited by 59
Self-citationThe pediatric hydroxyurea phase III clinical trial (BABY HUG): Challenges of study design
Thompson, B. W., Miller, S. T., Rogers, Z. R., Rees, R. C., Ware, R. E., Waclawiw, M. A., Iyer, R. V., Casella, J. F., Luchtman‐Jones, L., RANA, S. R., et al. (2009) · Pediatric Blood & Cancer · doi:10.1002/pbc.22269 · Cited by 59
Self-citationHydroxyurea for sickle cell disease
Jones, A. P., Davies, S. C., & Olujohungbe, A. (2001) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002202 · Cited by 55
Chemical and Functional Analysis of Hydroxyurea Oral Solutions
Heeney, M. M., Whorton, M. R., Howard, T. A., Johnson, C. A., & Ware, R. E. (2004) · Journal of Pediatric Hematology/Oncology · doi:10.1097/00043426-200403000-00007 · Cited by 52
Self-citationMiller, S. T., Wang, W. C., Iyer, R. V., RANA, S. R., Lane, P. A., Ware, R. E., Li, D., & Rees, R. C. (2009) · Pediatric Blood & Cancer · doi:10.1002/pbc.22189 · Cited by 31
Self-citationSantos, A. O., Pinheiro, V. R. P., Anjos, A., Brandalise, S. R., Fahel, F., Lima, M., Etchebehere, E., Ramos, C. D., & Camargo, E. E. (2002) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-001-0738-5 · Cited by 29
Fukuchi, Y., Shibata, F., Ito, M., Goto‐Koshino, Y., Sotomaru, Y., Ito, M., Kitamura, T., & Nakajima, H. (2005) · Blood · doi:10.1182/blood.v106.11.2264.2264 · Cited by 2
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Yawn, B. P., Buchanan, G. R., Afenyi-Annan, A. N., Ballas, S. K., Hassell, K. L., James, A. H., Jordan, L., Lanzkron, S. M., Lottenberg, R., Savage, W. J., et al. (2014) · JAMA · doi:10.1001/jama.2014.10517 · Cited by 1,599
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Metadata
- Authors
- Wang, W. C., Ware, R. E., Miller, S. T., Iyer, R. V., Casella, J. F., Minniti, C. P., Rana, S., Thornburg, C. D., Rogers, Z. R., Kalpatthi, R. V., Barredo, J. C., Brown, R. C., Sarnaik, S. A., Howard, T. H., Wynn, L. W., Kutlar, A., Armstrong, F. D., Files, B. A., Goldsmith, J. C., Waclawiw, M. A., Huang, X., & Thompson, B. W.
- Affiliations
- St. Jude Children's Research Hospital (US)
- SUNY Downstate Health Sciences University (US)
- University of Mississippi Medical Center (US)
- Johns Hopkins University (US)
- Children's National (US)
- Howard University (US)
- Duke Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
- Medical University of South Carolina (US)
- University of Miami (US)
- Children's Hospital of Michigan (US)
- University of Alabama at Birmingham (US)
- Augusta University (US)
- Emory University (US)
- National Heart, Lung, and Blood Institute (US)
- Clinical Trials and Surveys Corporation (US)
- Corresponding author
- Wang, Winfred C
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 377
- Issue
- 9778
- Pages
- 1663-1672
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC3133619
- OpenAlex
- W2170086069
- Semantic Scholar
- 007f7341f1586c3f34ecd96fa415bd95116f1c85
- Cited by
- 803
- References
- 35
- Citations by year
- 2026: 46 · 2025: 42 · 2024: 57 · 2023: 49 · 2022: 58 · 2021: 54 · 2020: 58 · 2019: 67 · 2018: 50 · 2017: 64 · 2016: 52 · 2015: 61 · 2014: 50 · 2013: 45 · 2012: 25
- FWCI
- 21.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hb07156-19-0-1, n01hb07159-25-0-1, n01hb07153-18-0-1, n01hb07155-16-0-0, n01hb07158-17-0-0, n01hb07157-15-0-0, n01hb07152-18-0-0, n01hb07151-17-0-0, n01hb07150-20-0-1, n01hb07160-38-0-1, n01hb07154-21-0-0)
- National Heart, Lung, and Blood Institute (N01-HB-07154, N01-HB-07157, N01-HB-07160, N01 HB007155, N01-HB07155, N01-HB-07152, N01-HB-07153, N01 HB007150, N01-HB-07151, N01-HB-07158, N01-HB-07150, N01 HB007160, N01-HB-07159, N01-HB-07156)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- hydroxyurea, sickle cell disease, infants, spleen function, renal function, acute chest syndrome, pain episodes, fetal hemoglobin, brain development, mutagenicity, drug toxicity, beta-thalassemia, organ dysfunction, growth, transcranial Doppler, glomerular filtration rate, urine osmolality
- MeSH terms
- Anemia, Sickle Cell, Antisickling Agents, Blood Cell Count, Child Development, Female, Glomerular Filtration Rate, Hemoglobins, Humans, Hydroxyurea, Infant, Male, Osmolar Concentration, Pain, Spleen, United States, Urine, Biomarkers, Technetium Tc 99m Pentetate, Treatment Outcome, Ultrasonography, Doppler, Transcranial, Acute Chest Syndrome
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