• DNA damage from hydroxyurea therapy-variable-diversity-joining (VDJ) recombination events defined as the number of events per microgram of genomic DNA; [ Time Frame: Every 3 years ] [ Designated as safety issue: Yes ]
  
• DNA damage from hydroxyurea therapy-chromosomal breakage studies with quantitation of microdeletions [ Time Frame: Every 3 years ] [ Designated as safety issue: Yes ]
  
• DNA damage from hydroxyurea therapy-hypoxanthine phosphoribosyl transferase (HPRT) mutant frequency [ Time Frame: Every 3 years ] [ Designated as safety issue: Yes ]
  
• DNA damage from hydroxyurea therapy-percentage of HJB in immature (CD71+) erythrocytes [ Time Frame: Once per year (6 times in first year for participants who are initiating HU therapy) ] [ Designated as safety issue: Yes ]
  
• Pharmacokinetic measures (maximum plasma concentration (Cmax), plasma half-life (T ½), and total plasma concentration-versus-time or "area under the curve" (AUC) as previously described for hydroxyurea absorption [ Time Frame: Baseline (pre-HU therapy) and ~12 months after HU therapy is initiated ] [ Designated as safety issue: No ]
  

• Brain function as measured by MRI/MRA and TCD [ Time Frame: Every 3 years ] [ Designated as safety issue: No ]
  
• Splenic function as measured by Spleen Scan [ Time Frame: Every 3 years ] [ Designated as safety issue: No ]
  
• Kidney function as measured by BUN/creatinine and Urinalysis [ Time Frame: Every 12 months ] [ Designated as safety issue: No ]
  
• Lung function as measured by forced vital capacity (FVC) (%), forced vital volume in 1 second (FVC1) (%), and tricuspid regurgitation (TR) jet on Echocardiogram (ECHO) [ Time Frame: Every 3 years ] [ Designated as safety issue: No ]
  
• Growth as measured by height and weight [ Time Frame: Every 3 years ] [ Designated as safety issue: No ]
  
• Variability in hydroxyurea response at maximum tolerated dose (MTD) as measured by analyzing methylation patterns and genetic variations in the globin genes, and by performing microarray analysis of circulating blood cell mRNA expression [ Time Frame: Baseline and ~12 months ] [ Designated as safety issue: No ]
  

Many years of study have documented the severe effects of sickle cell disease. Some of these effects include hemolysis (the break down of red blood cells), blockages in the blood vessels, and damage to the organs systems of the body. Hydroxyurea, which is given by mouth, is used to effectively prevent blockages in the blood vessels of patients with sickle cell disease. The hydroxyurea dosage varies and the responses of the body to this drug are not well understood. This study will follow sickle cell patients being treated with hydroxyurea for a long period of time to evaluate the long-term cellular and molecular effects of the drug on the patients' body. This study will consist of two patient groups. One group will be made up of patients who have received hydroxyurea therapy before entering the study (Old Cohort). The second group will be made up of patients who have not received hydroxyurea before study entry (New Cohort). Participants from the New Cohort will have pharmacokinetic studies done at baseline and at 12 months; Old Cohort participants will have PK studies performed only once, when they are at their maximum tolerated dose. This is not a therapeutic drug trial. Subjects for this study will receive hydroxyurea therapy for accepted clinical indications, and will be treated per best clinical management using treatment algorithms established at St. Jude Children's Research Hospital and other pediatric sickle cell programs across the United States.

Hydroxyurea therapy data (such as dosing and duration of therapy) will not be dictated by this study, but will be collected to correlate with long-term outcomes. Hydroxyurea dose escalation to a stable MTD will occur according to published guidelines.