Hydroxyurea for Sickle Cell Anemia: What Have We Learned and What Questions Still Remain?

Overview

Journal Curr Opin Hematol

Specialty Hematology

Date 2011 Mar 5

PMID 21372708

Citations 65

Authors

Patrick T McGann

Russell E Ware

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: Sickle cell anemia (SCA) is a well characterized severe hematological disorder with substantial morbidity and early mortality. Hydroxyurea is a potent inducer of fetal hemoglobin, and evidence over the past 25 years has documented its laboratory and clinical efficacy for both adults and children with SCA.

Recent Findings: The phase III study of hydroxyurea in infants (BABY HUG) has just been completed and preliminary results indicate equivocal benefits for organ protection during the 2-year treatment period, but significant benefits for pain, acute chest syndrome, hospitalizations, and transfusions. Three new reports document the benefits of hydroxyurea on reducing mortality in SCA: two adult trials (LaSHS and MSH) and one pediatric study (Brazilian cohort). Recent results from the HUSTLE protocol suggest minimal genotoxicity or carcinogenicity with long-term hydroxyurea exposure.

Summary: The potential utility of hydroxyurea for all patients with SCA is clear and indisputable. With decades of accumulated evidence and documented efficacy with an acceptable long-term safety profile, it is time to consider hydroxyurea treatment the standard of care for all young patients with SCA. Exporting our knowledge and experience with hydroxyurea to developing nations with large medical burdens from SCA can help relieve global suffering from this condition.

Citing Articles

Emergencies in Hematology: Why, When and How I Treat?.

Duminuco A, Del Fabro V, De Luca P, Leotta D, Limoli M, Longo E J Clin Med. 2025; 13(24.

PMID: 39768494 PMC: 11728391. DOI: 10.3390/jcm13247572.

Global profiling of protein complex dynamics with an experimental library of protein interaction markers.

Dorig C, Marulli C, Peskett T, Volkmar N, Pantolini L, Studer G Nat Biotechnol. 2024; .

PMID: 39415059 DOI: 10.1038/s41587-024-02432-8.

Post-GWAS Validation of Target Genes Associated with HbF and HbA Levels.

Caria C, Faa V, Porcu S, Marongiu M, Poddie D, Perseu L Cells. 2024; 13(14.

PMID: 39056767 PMC: 11274989. DOI: 10.3390/cells13141185.

Pharmacokinetic-Guided Hydroxyurea to Reduce Transfusions in Ugandan Children with Sickle Cell Anemia: Study Design of the Alternative Dosing And Prevention of Transfusions Trial.

Power-Hays A, Namazzi R, Kato C, McElhinney K, Conroy A, Hume H Acta Haematol. 2024; :1-12.

PMID: 38824918 PMC: 11617603. DOI: 10.1159/000539541.

Predictors of Intensive Care Admission Among Adult Patients with Sickle Cell Disease in Eastern Province of Saudi Arabia.

Alsalman M, Alsalman Z, Alkhalifa H, Alfaraj A, Alkhalifah A, Almulihi Q J Blood Med. 2024; 14:671-680.

PMID: 38162949 PMC: 10757811. DOI: 10.2147/JBM.S435861.

References

Elford H . Effect of hydroxyurea on ribonucleotide reductase. Biochem Biophys Res Commun. 1968; 33(1):129-35. DOI: 10.1016/0006-291x(68)90266-0. View

cokic V, Andric S, Stojilkovic S, Noguchi C, Schechter A . Hydroxyurea nitrosylates and activates soluble guanylyl cyclase in human erythroid cells. Blood. 2007; 111(3):1117-23. PMC: 2214757. DOI: 10.1182/blood-2007-05-088732. View

Lori F, Malykh A, Cara A, Sun D, Weinstein J, Lisziewicz J . Hydroxyurea as an inhibitor of human immunodeficiency virus-type 1 replication. Science. 1994; 266(5186):801-5. DOI: 10.1126/science.7973634. View

Platt O, Brambilla D, Rosse W, Milner P, Castro O, Steinberg M . Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994; 330(23):1639-44. DOI: 10.1056/NEJM199406093302303. View

Thornburg C, Dixon N, Burgett S, Mortier N, Schultz W, Zimmerman S . A pilot study of hydroxyurea to prevent chronic organ damage in young children with sickle cell anemia. Pediatr Blood Cancer. 2008; 52(5):609-15. PMC: 5600482. DOI: 10.1002/pbc.21738. View

Zimmerman S, Schultz W, Burgett S, Mortier N, Ware R . Hydroxyurea therapy lowers transcranial Doppler flow velocities in children with sickle cell anemia. Blood. 2007; 110(3):1043-7. DOI: 10.1182/blood-2006-11-057893. View

Conley C, Weatherall D, RICHARDSON S, SHEPARD M, CHARACHE S . Hereditary persistence of fetal hemoglobin: a study of 79 affected persons in 15 Negro families in Baltimore. Blood. 1963; 21:261-81. View

Weinlich G, Schuler G, Greil R, Kofler H, Fritsch P . Leg ulcers associated with long-term hydroxyurea therapy. J Am Acad Dermatol. 1998; 39(2 Pt 2):372-4. DOI: 10.1016/s0190-9622(98)70394-9. View

Ware R, Rees R, Sarnaik S, Iyer R, Alvarez O, Casella J . Renal function in infants with sickle cell anemia: baseline data from the BABY HUG trial. J Pediatr. 2009; 156(1):66-70.e1. PMC: 4755353. DOI: 10.1016/j.jpeds.2009.06.060. View

10.

Kennedy B, Yarbro J . Metabolic and therapeutic effects of hydroxyurea in chronic myeloid leukemia. JAMA. 1966; 195(12):1038-43. View

11.

Powars D, Chan L, Hiti A, Ramicone E, Johnson C . Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore). 2005; 84(6):363-376. DOI: 10.1097/01.md.0000189089.45003.52. View

12.

Oppenheim J, FISHBEIN W . Induction of chromosome breaks in cultured normal human leukocytes by potassium arsenite, hydroxyurea and related compounds. Cancer Res. 1965; 25(7):980-5. View

13.

Allon M . Renal abnormalities in sickle cell disease. Arch Intern Med. 1990; 150(3):501-4. View

14.

Platt O, Orkin S, Dover G, Beardsley G, Miller B, Nathan D . Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J Clin Invest. 1984; 74(2):652-6. PMC: 370519. DOI: 10.1172/JCI111464. View

15.

Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F . Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995; 332(17):1132-6. DOI: 10.1056/NEJM199504273321704. View

16.

Steinberg M, Barton F, Castro O, Pegelow C, Ballas S, Kutlar A . Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA. 2003; 289(13):1645-51. DOI: 10.1001/jama.289.13.1645. View

17.

WHITTEN C, YOUNES A . A comparative study of renal concentrating ability in children with sickel cell anemia and in normal children. J Lab Clin Med. 1960; 55:400-15. View

18.

Brawley O, Cornelius L, Edwards L, Gamble V, Green B, Inturrisi C . National Institutes of Health Consensus Development Conference statement: hydroxyurea treatment for sickle cell disease. Ann Intern Med. 2008; 148(12):932-8. DOI: 10.7326/0003-4819-148-12-200806170-00220. View

19.

Steinberg M, Mccarthy W, Castro O, Ballas S, Armstrong F, Smith W . The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up. Am J Hematol. 2010; 85(6):403-8. PMC: 2879711. DOI: 10.1002/ajh.21699. View

20.

CHARACHE S, Dover G, Moore R, Eckert S, Ballas S, Koshy M . Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia. Blood. 1992; 79(10):2555-65. View