Published online December 1, 2008
PEDIATRICS Vol. 122 No. 6 December 2008, pp. 1332-1342 (doi:10.1542/peds.2008-0441)
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Strouse, J. J.
Right arrow Articles by Segal, J. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Strouse, J. J.
Right arrow Articles by Segal, J. B.
Related Collections
Right arrow Blood
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

REVIEW ARTICLE

Hydroxyurea for Sickle Cell Disease: A Systematic Review for Efficacy and Toxicity in Children

John J. Strouse, MDa, Sophie Lanzkron, MDb, Mary Catherine Beach, MD, MPHc, Carlton Haywood, MSd, Haeseong Park, MDc,e, Catherine Witkop, MD, MPHf, Renee F. Wilson, MScc, Eric B. Bass, MD, MPHc and Jodi B. Segal, MD, MPHc

a Division of Pediatric Hematology, Department of Pediatrics
b Divisions of Hematology
c General Internal Medicine, Department of Medicine
e Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
d Departments of Health Policy and Management
f General Preventive Medicine, Bloomberg School of Public Health, Baltimore, Maryland

CONTEXT. Hydroxyurea is the only approved medication for the treatment of sickle cell disease in adults; there are no approved drugs for children.

OBJECTIVE. Our goal was to synthesize the published literature on the efficacy, effectiveness, and toxicity of hydroxyurea in children with sickle cell disease.

METHODS. Medline, Embase, TOXLine, and the Cumulative Index to Nursing and Allied Health Literature through June 2007 were used as data sources. We selected randomized trials, observational studies, and case reports (English language only) that evaluated the efficacy and toxicity of hydroxyurea in children with sickle cell disease. Two reviewers abstracted data sequentially on study design, patient characteristics, and outcomes and assessed study quality independently.

RESULTS. We included 26 articles describing 1 randomized, controlled trial, 22 observational studies (11 with overlapping participants), and 3 case reports. Almost all study participants had sickle cell anemia. Fetal hemoglobin levels increased from 5%–10% to 15%–20% on hydroxyurea. Hemoglobin concentration increased modestly (~1 g/L) but significantly across studies. The rate of hospitalization decreased in the single randomized, controlled trial and 5 observational studies by 56% to 87%, whereas the frequency of pain crisis decreased in 3 of 4 pediatric studies. New and recurrent neurologic events were decreased in 3 observational studies of hydroxyurea compared with historical controls. Common adverse events were reversible mild-to-moderate neutropenia, mild thrombocytopenia, severe anemia, rash or nail changes (10%), and headache (5%). Severe adverse events were rare and not clearly attributable to hydroxyurea.

CONCLUSIONS. Hydroxyurea reduces hospitalization and increases total and fetal hemoglobin levels in children with severe sickle cell anemia. There was inadequate evidence to assess the efficacy of hydroxyurea in other groups. The small number of children in long-term studies limits conclusions about late toxicities.

Key Words: hydroxyurea • sickle cell disease • systematic review • efficacy • toxicity

Abbreviations: SCD—sickle cell disease • ACS—acute chest syndrome • HbSS—sickle cell anemia • HbF—fetal hemoglobin • RCT—randomized, controlled trial • AHRQ—Agency for Healthcare Research and Quality • MTD—maximum tolerated dose • HUSOFT—Hydroxyurea Safety and Organ Toxicity • TCD—transcranial Doppler • ANC—absolute neutrophil count • HPRT—hypoxanthine phosphoribosyl transferase

Accepted Mar 18, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 PediatricsHome page
B. U. Mueller
When Should Hydroxyurea Be Used for Children With Sickle Cell Disease?
Pediatrics, December 1, 2008; 122(6): 1365 - 1366.
[Full Text] [PDF]