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Objective: To synthesize the published literature on the efficacy, effectiveness, and
toxicity of hydroxyurea (HU) when used for treatment of sickle cell disease (SCD); and
to review the evidence regarding barriers to its use.
Data Sources: Articles cited in MEDLlNE®, EMBASE, TOXLine, and CINAHL through June 30, 2007.
Review Methods: Paired reviewers reviewed each title, abstract, and article to assess
eligibility. They abstracted data sequentially and then independently graded the evidence.
Results: In one small, randomized trial of HU in children with SCD; the yearly
hospitalization rate was lower with HU than placebo (1.1 versus 2.8, p=0.002). The
absolute increase in fetal hemoglobin (Hb F%) was 10.7 percent. Twenty observational
studies of HU in children reported similar increases in Hb F%, while hemoglobin
concentration increased by roughly 1 g/dl.
One large randomized trial tested the efficacy of HU in adults with SCD and found
that after 2 years of treatment, Hb F% increased by 3.2 percent and hemoglobin increased
by 0.6 g/dl, The median number of painful crises was 44 percent (p<0.001) lower among
patients treated with HU. The 12 observational studies of HU enrolling adults with SCD
supported these findings.
Panelists from the Center for the Evaluation of Risks to Human Reproduction
reviewed the literature for potential toxicities of HU. They concluded that HU does not
cause a growth delay in children 5-15 years old. There were no data on the effects on
subsequent generations following exposure of developing germ cells to HU in utero.
Some evidence supported impaired spermatogenesis with use of HU. Although we
identified six patients taking HU who developed leukemia, the evidence did not support
causality. Similarly, the evidence suggested no association between HU and leg ulcers in
patients with SCD, although there was in patients with other illnesses. The literature
supported neutropenia, skin rashes and nail changes associated with use of HU, but was
sparse regarding skin neoplasms or other secondary malignancies in SCD.
Only two studies investigated barriers to use of HU. Perceived efficacy and perceived
safety of HU had the largest influence on patients' (or parents') choice to use HU.
Providers reported barriers to be patient concerns about side effects; and their own
concerns about HU in older patients, patient compliance, lack of contraception, side
effects and carcinogenic potential, doubts about effectiveness, and concern about costs.
Conclusions: HU is efficacious in children and adults with SCD; with an increase in Hb
F%, and reduction in hospitalizations and pain crises. However, few studies have
measured the effectiveness of HU for SCD in usual practice. The paucity of long-term
studies limits conclusions about toxicities and about mortality. Future studies of
interventions to overcome the barriers to use of HU in patients with SCD are necessary.
Hydroxyurea for the Treatment of Sickle Cell Disease
Evidence-based Practice Center: Johns Hopkins University
Topic Nominators: National Institutes of Health Office of Medical Applications of Research
Current as of February 2008
Hydroxyurea for the Treatment of Sickle Cell Disease, Structured Abstract. February 2008. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/tp/hydscdtp.htm