Risk Stratification for Clinical Severity of Sickle Cell Disease in Nigeria and Assessment of Efficacy and Safety During Treatment With Hydroxyurea

The vast majority of births with sickle cell disease (SCD) occur in Africa and 90% are
thought to die before the age of five. Hydroxyurea (HU) is the only drug approved by the FDA
for the treatment of sickle cell anemia. Although HU is used to treat small numbers of
patients in Africa, cost, fear of toxicity, and lack of awareness and availability limit its
use. The leukopenia that may be seen with HU raises the possibility of increased
susceptibility to infection. Risk stratification - i.e., identification of patients most
likely to benefit- could focus therapy and provide confidence that the risk:benefit ratio is
favorable. Several clinical measures of future risk are well defined and findings on modifier
genes in the US, primarily related to fetal hemoglobin (HbF), have further improved risk
prediction. Whether the genetic variants predict severity in Africa is not known. The
investigators have established a SCD cohort in Ibadan, Nigeria. In the first phase of this
research the investigators will implement clinical risk examinations and assess the
relationship between clinical characteristics (including levels of HbF) and known genetic
markers. As a proxy for a birth cohort, the investigators will compare the frequency of the
genetic markers in adult patients (i.e., "survivors") to children. In the second phase the
investigators will randomize 40 high risk adult patients to fixed low dose HU or no HU
treatment in a crossover design and monitor hematologic and physiologic parameters to
document hematologic effects and safety. This work will lay the basis for a large-scale trial
to document safety and efficacy.