title: Systematic review: Hydroxyurea for the treatment of adults with sickle cell disease.
abstract: BACKGROUND
  Hydroxyurea is the only approved drug for treatment of sickle cell disease.
  
  
  OBJECTIVE
  To synthesize the published literature on the efficacy, effectiveness, and toxicity of hydroxyurea when used in adults with sickle cell disease.
  
  
  METHODS
  MEDLINE, EMBASE, TOXLine, and CINAHL were searched through 30 June 2007.
  
  
  METHODS
  Randomized trials, observational studies, and case reports evaluating efficacy and toxicity of hydroxyurea in adults with sickle cell disease, and toxicity studies of hydroxyurea in other conditions that were published in English.
  
  
  METHODS
  Paired reviewers abstracted data on study design, patient characteristics, and outcomes sequentially and did quality assessments independently.
  
  
  RESULTS
  In the single randomized trial, the hemoglobin level was higher in hydroxyurea recipients than placebo recipients after 2 years (difference, 6 g/L), as was fetal hemoglobin (absolute difference, 3.2%). The median number of painful crises was 44% lower than in the placebo group. The 12 observational studies that enrolled adults reported a relative increase in fetal hemoglobin of 4% to 20% and a relative reduction in crisis rates by 68% to 84%. Hospital admissions declined by 18% to 32%. The evidence suggests that hydroxyurea may impair spermatogenesis. Limited evidence indicates that hydroxyurea treatment in adults with sickle cell disease is not associated with leukemia. Likewise, limited evidence suggests that hydroxyurea and leg ulcers are not associated in patients with sickle cell disease, and evidence is insufficient to estimate the risk for skin neoplasms, although these outcomes can be attributed to hydroxyurea in other conditions.
  
  
  CONCLUSIONS
  Only English-language articles were included, and some studies were of lower quality.
  
  
  CONCLUSIONS
  Hydroxyurea has demonstrated efficacy in adults with sickle cell disease. The paucity of long-term studies limits conclusions about toxicity.
authors.affiliation: School of Medicine ,Johns Hopkins University, 1830 East Monument Street, Suite 7300, Baltimore, MD 21205, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lanzkron
authors.forename: John J
authors.initials: JJ
authors.lastname: Strouse
authors.forename: Renee
authors.initials: R
authors.lastname: Wilson
authors.forename: Mary Catherine
authors.initials: MC
authors.lastname: Beach
authors.forename: Carlton
authors.initials: C
authors.lastname: Haywood
authors.forename: HaeSong
authors.initials: H
authors.lastname: Park
authors.forename: Catherine
authors.initials: C
authors.lastname: Witkop
authors.forename: Eric B
authors.initials: EB
authors.lastname: Bass
authors.forename: Jodi B
authors.initials: JB
authors.lastname: Segal
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy*; D000986:Antisickling Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005319:Fetal Hemoglobin / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000627:therapeutic use*; D007871:Leg Ulcer / Q000139:chemically induced; D008297:Male; D010146:Pain / Q000517:prevention & control; D013091:Spermatogenesis / Q000187:drug effects
chemical_list: D000986:Antisickling Agents; D006454:Hemoglobins; D005319:Fetal Hemoglobin; D006918:Hydroxyurea