A two-year pilot trial of hydroxyurea in very young children with sickle-cell anemia.

OBJECTIVE: Hydroxyurea improves hematologic values and decreases vaso-occlusive complications in adults and children with sickle cell anemia (SCA), but has not been tested in infants before the onset of chronic organ dysfunction. We conducted a collaborative pilot trial of hydroxyurea in infants with SCA to assess its (1) feasibility of administration, (2) toxicity, (3) hematologic effects, and (4) effect on spleen function. STUDY DESIGN: Patients with hemoglobin (Hb) SS or Sbeta(0) thalassemia (n = 28, median age 15 months) received hydroxyurea for 2 years at 20 mg/kg/day. Hydroxyurea was temporarily discontinued for predefined toxicity. RESULTS: Seven patients exited the study early: five for noncompliance or refusal to continue, one for mild stroke, and one for fatal splenic sequestration. The predominant toxicity was transient neutropenia, which was usually associated with a viral-like illness. After 2 years of treatment, mean Hb level = 8.8 g/dL and Hb F = 20.3%, both higher than predicted age-specific levels. Radionuclide splenic uptake was absent in 47% of patients at study completion, compared with predicted functional asplenia in 80% of the patients. CONCLUSIONS: Hydroxyurea therapy for infants with SCA is feasible and well tolerated, has hematologic efficacy, and may delay functional asplenia. The potential for hydroxyurea to preserve organ function in SCA should be further evaluated.

Abnormalities of the central nervous system in very young children with sickle cell anemia.

OBJECTIVE: To determine whether abnormalities of the CNS are present in very young children with sickle cell anemia. STUDY DESIGN: Thirty-nine children with hemoglobin SS between the ages of 7 and 48 months were examined with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). No child had a history of clinical stroke, although 3 had a history of seizures (2 neonatal). Twenty-one patients underwent developmental testing with the Bayley or McCarthy Scales. RESULTS: The overall prevalence of CNS abnormalities in asymptomatic children was 4 of 36 (11%, confidence interval 3, 26%). One patient had a silent infarct observed on MRI and a stenotic lesion on MRA; 3 other patients had stenotic lesions on MRA. The 3 patients who had a history of seizures all had lesions consistent with infarcts on MRI. Of the asymptomatic patients who had psychometric testing, 1 of 18 was developmentally delayed. One of 3 with a history of seizures had mild developmental delay. CONCLUSIONS: Very young children with sickle cell anemia (and no history of clinical stroke) have infarction in the brain and/or stenosis of major cerebral arteries, similar to those reported in older children. These findings indicate a need for larger studies to define the incidence of CNS lesions in this age group and to determine the need for early therapeutic intervention to prevent CNS sequelae of sickle cell disease.