Hydroxyurea therapy for pediatric patients with hemoglobin SC disease.
OBJECTIVE
Hydroxyurea (HU) has laboratory and clinical efficacy in hemoglobin SS (HbSS) disease, but its benefits in hemoglobin SC (HbSC) disease are unknown. A recent adult HbSC disease pilot trial with HU therapy documented a modest laboratory benefit. Our goal was to evaluate the laboratory and clinical responses of selected pediatric patients with severe HbSC disease to HU therapy.


METHODS
As part of a retrospective case series, patients were selected from the Duke Pediatric Sickle Cell Program based on the frequency and severity of their vasoocclusive events or an episode of acute chest syndrome. Oral HU therapy was started as a single daily dose and increased to the maximally tolerated dose based on myelosuppression. Laboratory evaluation was performed at baseline and monthly thereafter. Once the maximum tolerated dose was reached, laboratory data were monitored bimonthly.


RESULTS
We treated six severely affected pediatric HbSC patients with HU for a median of 27 months. Mean corpuscular volume increased significantly (+26 fL) without change in hemoglobin concentration (-0.1 g/dL); neutrophils decreased significantly. Percentage of fetal hemoglobin (+8.5%) and percentage of F cells (+35.7%) increased significantly. Two experienced only mild and reversible toxicity.


CONCLUSIONS
The laboratory responses in our pediatric patients with HbSC disease were striking, with increases in percentage of fetal hemoglobin and percentage of F-cells approaching responses observed in adult and pediatric patients with HbSS disease. All patients improved clinically. Our findings demonstrate that HU therapy benefits pediatric patients with severe HbSC disease, although larger clinical trials of HU therapy in HbSC disease are warranted.
Miller
M K
MK
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Zimmerman
S A
SA
Schultz
W H
WH
Ware
R E
RE
D000208:Acute Disease; D000293:Adolescent; D000986:Antisickling Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000517:prevention & control; D002637:Chest Pain / Q000209:etiology / Q000517:prevention & control; D002648:Child; D004417:Dyspnea / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006450:Hemoglobin SC Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013577:Syndrome; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D000986:Antisickling Agents; D006918:Hydroxyurea