Hydroxyurea as an alternative to blood transfusions for the prevention of recurrent stroke in children with sickle cell disease

Children with sickle cell disease (SCD) and stroke receive chronic transfus ions to prevent stroke recurrence. Transfusion risks including infection, e rythrocyte allosensitization, and iron overload suggest a need for alternat ive therapies. We previously used hydroxyurea (HU) and phlebotomy in two yo ung adults with SCD and stroke as an alternative to transfusions. We have n ow prospectively discontinued transfusions in 16 pediatric patients with SC D and stroke. Reasons to discontinue transfusions included erythrocyte allo antibodies or autoantibodies, recurrent stroke on transfusions, iron overlo ad, noncompliance, and deferoxamine allergy. HU was started at 15 mg/kg/d a nd escalated to 30 mg/kg/d based on hematologic toxicity. Patients with iro n overload underwent phlebotomy. The children have been off transfusions 22 months, (range, 3 to 52 months). Their average HU dose is 24.9 +/- 4.2 mg/ kg/d, hemoglobin concentration is 9.4 +/- 1.3 g/dL and mean corpuscular vol ume (MCV) is 112 +/- 9 fL. Maximum percentage fetal hemoglobin (%HbF) is 20 .6% +/- 8.0% and percentage HbF-containing erythrocytes (%F cells) is 79.3% +/- 14.7%. Fourteen patients underwent phlebotomy with an average of 8,993 mL(267 mL/kg) removed. Serum ferritin has decreased from 2,630 to 424 ng/m L, and 4 children have normal ferritin values. Three patients (19%) had neu rological events considered recurrent stroke, each 3 to 4 months after disc ontinuing transfusions, but before maximal HU effects. These preliminary da ta suggest some children with SCD and stroke may discontinue chronic transf usions and use HU therapy to prevent stroke recurrence. Phlebotomy is well- tolerated and significantly reduces iron overload. Modifications in HU ther apy to raise HbF more rapidly might increase protection against stroke recu rrence. (C) 1999 by The American Society of Hematology.