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Hydroxyurea therapy in children severely affected with sickle cell disease
J P Scott1, C A Hillery, E R Brown
1Department of Pediatrics, Medical College of Wisconsin, Milwaukee, USA.
Insights
Hydroxyurea therapy in children with severe sickle cell disease (SCD) improved blood counts and showed a trend toward fewer hospitalizations. This pilot study suggests hydroxyurea is a safe and potentially effective treatment for pediatric SCD.
Area of Science:
- Hematology
- Pediatric Medicine
- Pharmacology
Background:
- Sickle cell disease (SCD) presents with hemolytic anemia, infection risk, and painful vaso-occlusive events.
- Current treatments for severe SCD in children are limited, particularly for recurrent painful episodes.
- Hydroxyurea, an antimetabolite, is known to increase fetal hemoglobin (HbF) in adults with SCD.
Purpose of the Study:
- To evaluate the safety and efficacy of hydroxyurea in treating severe sickle cell disease (SCD) in pediatric patients.
- To assess hydroxyurea's impact on hematologic parameters and vaso-occlusive events in children with severe SCD.
Main Methods:
- A pilot trial involving 15 children with severe SCD (hemoglobin SS, SS-alpha thalassemia, or S-beta0-thalassemia) was conducted.
- Hydroxyurea was administered at 10-20 mg/kg/day, with dose escalation as tolerated.
- Patients were monitored for hematologic changes and compared pre- and post-treatment hospitalization rates (inpatient days).
Main Results:
- Hydroxyurea treatment led to significant increases in hemoglobin concentration, mean corpuscular volume, and HbF, with a decrease in bilirubin.
- Hospitalizations decreased significantly in children completing at least one year of treatment (p=0.03).
- Adverse effects included reversible myelotoxicity in three patients, with two requiring blood transfusions.
Conclusions:
- Hydroxyurea treatment in children with severe SCD demonstrated improved hematologic parameters and acceptable toxicity.
- A trend towards reduced hospitalizations was observed, suggesting potential efficacy.
- Further prospective, controlled trials are warranted to confirm hydroxyurea's effectiveness in pediatric SCD.
Hypothesis:
The major clinical manifestations of sickle cell disease (SCD) are hemolytic anemia, predisposition to infection, and recurrent vaso-occlusive episodes resulting in pain, organ dysfunction, or both. There has been no satisfactory treatment for children with recurrent severe painful episodes caused by SCD. Hydroxyurea is an antimetabolite drug shown in adults with SCD to increase fetal hemoglobin levels and reduce the symptoms of SCD. We hypothesized that hydroxyurea therapy in children with severe (defined as > or = 3 vaso-occlusive events per year) SCD could improve hematologic parameters and reduce vaso-occlusive events.
Objective:
To assess the safety and efficacy of hydroxyurea for the treatment of severe SCD in children.
Study Design:
After obtaining informed consent, we initiated hydroxyurea therapy at a dosage of 10 to 20 mg/kg per day in 15 patients with severe SCD (hemoglobin SS, hemoglobin SS-alpha thalassemia, or hemoglobin S-beta0-thalassemia). Doses were escalated as tolerated. Patients were monitored with bimonthly physical examinations and monthly laboratory measures. To assess the impact of hydroxyurea on clinical symptoms, we recorded the number of inpatient days for each patient during the period of treatment and compared it with the number of inpatient days for the 12- to 24-month period before institution of hydroxyurea therapy, using the subject as his or her own control subject.
Results:
Thirteen patients received hydroxyurea for a median of 24 months (range, 6 to 39 months). The mean dose of hydroxyurea was 21.4 +/- 5.2 mg/kg. Treatment with hydroxyurea induced statistically significant increases in the total hemoglobin concentration, mean corpuscular volume, and percentage of hemoglobin F, and a decrease in the serum concentration of bilirubin. Toxic effects included three episodes of a reversible myelotoxic reaction, two of which required transfusion of packed erythrocytes. For the entire group, hospitalization decreased from a prehydroxyurea median of 3.9 +/- 2.0 days per month to 1.1 +/- 2.1 days per month of therapy (p = 0.09). For those subjects (n = 10) completing at least 1 year of treatment, the decrease in hospitalization from 4.1 +/- 2.2 to 1.0 +/- 1.7 days per month was significant (p = 0.03).
Conclusions:
In this pilot trial, hydroxyurea treatment of severe SCD in children was associated with improved hematologic parameters, acceptable toxic effects, and a trend to reduced hospitalization. Hydroxyurea appears to be a safe and potentially effective agent for the treatment of severe SCD in children. A prospective, controlled trial to investigate the efficacy of hydroxyurea in children is therefore warranted.