Clinical and hematologic effects of hydroxyurea in children with sickle cell anemia,☆☆,,★★

Presented in part at the twentieth annual meeting of the National Sickle Cell Disease Program, Boston, Mass., March 18-21, 1995 (abstract 175).
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Abstract

PURPOSE: This open-label pilot study was designed (1) to determine the effect of hydroxyurea on the hemoglobin level in children with sickle cell anemia, (2) to evaluate the toxicity of hydroxyurea, and (3) to assess any impact of hydroxyurea on the frequency of vaso-occlusive crises (VOCs). PATIENTS AND METHODS: Ten children (group 1) with three or more VOCs of the extremities or two or more VOCs of the lungs (acute chest syndrome) in the preceding 12 months, and five children (group 2) with hemoglobin levels less than 70 gm/L were treated with hydroxyurea in doses of 20 to 35 mg/kg per day. The frequency of VOCs before hydroxyurea therapy was compared with the frequency during therapy, and the peak hemoglobin levels during hydroxyurea therapy were compared with the pretreatment values. RESULTS: One patient in group 1 was removed from the study within 1 month because of nausea. Seven of the remaining nine patients in group 1 had a decrease in the frequency of VOCs. The number of VOCs per patient-year for all 14 patients decreased from 2.5 before hydroxyurea therapy to 0.87 during hydroxyurea therapy, a decrease of 65% (p <0.00001). Two of five patients in group 2 had an increase in hemoglobin of 27 gm/L and 34 gm/L over the baseline. The median rise in hemoglobin was 19 gm/L (range, 7 to 37) for all 14 patients. Nine patients are still receiving hydroxyurea for a median period of 23 months (range, 18 to 59). CONCLUSIONS: Hydroxyurea decreases the severity of anemia in some patients, and it may decrease the frequency of VOC. Its short-term hematologic toxicity is minimal. (J PEDIATR 1996;129:559-65)

Section snippets

Patients

(Table I). From October 1990 to November 1995, a total of 15 children (male/female ratio, 10:5) were enrolled in an open-label, single-arm hydroxyurea study approved by the institutional review board. The median age of the patients was 15.3 years (range, 4.4 to 18.8). Parental consent was obtained for all patients. Patients with SCA and frequent VOCs (group 1) or severe anemia (group 2) were considered eligible for study. Frequent VOC was defined as three or more hospitalizations for VOCs

Frequency of VOCs

When all 14 patients were considered, 138 VOCs occurred before hydroxyurea therapy during 55.2 patient-years of follow-up, for an average of 2.5 VOCs per patient-year (Table I). The total number of VOCs during hydroxyurea therapy was 31 in a period of 35.7 patient-years, for an average of 0.87 VOC per patient-year. This represents a 65% decrease in the frequency of VOCs and is statistically significant (p <0.00001).

Statistical analysis. On the basis of the pretreatment event rate of 2.5 events

DISCUSSION

In this open-label pilot study the number of VOCs per patient-year was significantly less during hydroxyurea therapy than during the pretherapy period (0.87 vs 2.5 VOCs; p <0.00001), representing a 65% reduction in the frequency of crises. However, because of the open-label design of the study, a placebo effect on decreasing the frequency of crises could not be ruled out.

A double-blind study of adults has recently shown that hydroxyurea decreases the frequency of crises by 44% in comparison

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  • From the Sections of Pediatric Hematology-Oncology and General Pediatrics, and the Department of Quantitative Health Sciences, New York Medical College, Valhalla

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    Supported in part by a grant from Healix Health Care Inc.

    Reprint requests: S. Jayabose, MD, New York Medical College, Munger Pavilion, R.110, Valhalla, NY 10595.

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