Hydroxyurea for sickle cell disease: a systematic review for efficacy and toxicity in children.
BACKGROUND
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 (approximately 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.
Strouse
John J
JJ
Department of Pediatrics, Johns Hopkins University School of Medicine, Division of Pediatric Hematology, 720 Rutland Ave, Ross 1125, Baltimore, MD 21205, USA. jstrous1@jhmi.edu
Lanzkron
Sophie
S
Beach
Mary Catherine
MC
Haywood
Carlton
C
Park
Haeseong
H
Witkop
Catherine
C
Wilson
Renee F
RF
Bass
Eric B
EB
Segal
Jodi B
JB
D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000175:diagnosis / Q000188:drug therapy*; D000986:Antisickling Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000986:Antisickling Agents; D006918:Hydroxyurea