Hydroxyurea and Transfusion

This is a single-arm, prospective study of hydroxyurea added to simple chronic transfusions,
combination treatment termed hydroxyurea and transfusion (HAT). The primary objective of the
study is to determine the feasibility of HAT for patients with sickle cell anemia (SCA)
currently being treated only with simple transfusions for stroke prevention. Secondary
objectives include: to evaluate the safety of HAT and to determine if HAT decreases
transfusion requirements in this patient population. Exploratory objectives include: to
evaluate with HAT changes in pre-transfusion laboratories and biomarkers of cerebrovascular
disease progression, and to describe changes on brain imaging.

Inclusion Criteria:

1. Diagnosis of SCA (Hb SS or Sβ0 thalassemia).

2. On simple chronic transfusion therapy for stroke prevention (primary or secondary
prevention) for ≥1 year with no plans to stop simple chronic transfusion in the next
year.

Exclusion Criteria:

1. Poor adherence to simple transfusion regimen as defined by having an HbS >45% at any
time in the last year AND a transfusion interval >5 weeks.

2. Treatment with hydroxyurea in the 12 months prior to study enrollment.

3. Abnormal initial laboratory values (temporary exclusions):

1. Absolute neutrophil count <1.5 x 10^9/L

2. Platelet count <100 x 10^9/L

3. Serum creatinine more than twice upper limit for age

4. Pregnancy or unwillingness to use a medically acceptable form of contraception if
sexually active.