ORLANDO -- Treatment with hydroxyurea significantly reduced the risk of death among children with severe sickle cell disease, a researcher reported here.
A 10-year retrospective study of almost 1,000 children found that the odds of dying were nearly five times higher for untreated children than for those treated with hydroxyurea, according to Clarisse Lobo, MD, of the Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti in Rio de Janeiro.
The compound also reduced the rate of blood transfusions, the number of emergency room visits, and the need for inpatient care, Lobo told reporters at the annual meeting of the American Society of Hematology.
Since 2000, Lobo said, she and her colleagues have offered hydroxyurea to children 3 years or older who met Brazilian health ministry criteria -- including children with at least two incidents of acute chest syndrome or at least three painful events in the previous year, persistent oxygen saturation of less than 94%, growth delay, and overt stroke where transfusion was contraindicated or refused.
In the U.S., similar findings have been seen in adults with sickle cell disease, but the compound is not approved for use in children.
But the findings of the Brazilian analysis are "reassuring" to U.S. clinicians who treat children off-label with the compound, according to Alexis Thompson, MD, of Northwestern University Feinberg School of Medicine in Chicago, who was not involved in the study, but who moderated a press conference at which it was presented.
Thompson said the research "underscores" that the compound can have important benefits for children with symptoms such as recurrent pain and acute chest syndrome.
Hydroxyurea, an anti-neoplastic agent, makes red blood cells less likely to bend into an abnormal sickle shape, helping to prevent severe pain crises and avoid blood transfusions in patients with sickle cell anemia.
For their analysis, Lobo and colleagues examined prospectively collected morbidity and mortality data for 965 children ages 3 through 18 treated at their center. Of those, 224 met the criteria for hydroxyurea treatment, she reported.
The drug was started at 15 milligrams per kilogram per day and increased to a maximum of 30 mg/kg per day, depending on hematologic toxicity. The median treatment duration for was 1.9 years and the median dose was 20 mg/kg per day.
Comparison of the two groups showed that among those children getting hydroxyurea:
- The need for inpatient care was reduced 67.9%, which was significant at P=0.002.
- Emergency room visits were down by 48.7%, which was significant at P<0.001.
- Transfusions during the treatment period were cut 36.3%, significant at P=0.001.
- There were no serious adverse events attributed to the drug.
- Only two of the 46 deaths occurred among treated patients. Most deaths were caused by acute chest syndrome -- 17 in the untreated group and both of the fatalities in the treated patients.
- The cumulative survival rates at 10 and 17.9 years were 99.4% and 97.4%, respectively, compared with 97.4% and 66.3% among those not treated, differences that were significant at P=0.027.
The odd ratio for death was 4.6 times higher among untreated patients, compared with those getting hydroxyurea, Lobo reported; the risk difference was significant at P=0.03.
"The mortality question in adults was answered some time ago," Thompson commented. "Lobo's work underscores that we may see the same benefits in children."
The study has demonstrated that drug is efficacious, she said. "The challenge now is effectiveness," Thompson said. "Unless we can get it out into wider use, we'll continue to see limited benefit from it."
The study was supported by the Hematology Institute of Rio de Janeiro. Lobo said she had no relevant disclosures.
Thompson had no relevant disclosures.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
American Society of HematologySource Reference: Lobo C, et al "Hydroxyurea therapy reduces mortality among children with sickle cell disease" ASH 2010; Abstract 843.