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Dosing of hydroxyurea (HU) in young patients with sickle cell anemia (SCA) should target a fetal hemoglobin (HbF) level above 20%, according to researchers.
Their study, HUSTLE, showed that children and adolescents who received a maximum tolerated dose (MTD) of HU were able to achieve HbF levels above 20%.
And patients who achieved such HbF levels had a significantly lower risk of hospitalization for any reason, including vaso-occlusive crisis, acute chest syndrome, and fever.
Jeremie Estepp, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these results in the American Journal of Hematology.
“Our analysis showed that, using this approach, hospitalizations for the average patient fell to less than 1 every couple of years rather than 4 to 6 annually,” Dr Estepp said. “This frees children from the fevers, pain, and other symptoms of this disease and gives them and their families more chances to enjoy childhood and adolescence.”
The study enrolled 230 SCA patients. Most had the HbSS genotype (n=214; 93%), although 7% (n=16) had HbSb0 thalassemia. The patients’ median age at HU initiation was 7.4 years (range, 6 months to 17.9 years). The mean HbF level at enrollment was 9.7%, and the median was 7.9% (range, 1.0-32.9%).
The researchers used a dose-escalation approach to determine the MTD of HU for each of the patients in this study. The MTD was defined by an absolute neutrophil count of 2000-4000 x 106/L or the presence of hematologic toxicity. The maximum absolute dose was 35 mg/kg/day or 2000 mg/day (whichever came first).
The mean daily dose of HU at the MTD was 26.7 mg/kg/day, and the median was 28.0 mg/kg/day (range, 13.0 to 35.0 mg/kg/day).
Three-quarters of patients (75.2%, 173/230) attained the MTD at the time of data censoring. Patients were followed for up to 4 years after study entry.
As far as treatment compliance, there were complete medication dispensation records available for 96% (220/230) of patients. And the patients were in possession of HU a mean of 93.6% of the time.
The researchers found that administering HU at the MTD resulted in a mean HbF of 26.7% and a median of 21.7% (interquartile range, 16.2% to 27.8%).
And the odds of being hospitalized were higher when a patient’s HbF level was less than 21%. The odds ratios for hospitalization were as follows:
- 4.1 for fever
- 2.6 for acute chest syndrome
- 2.2 for vaso-occlusive crisis
- 2.1 for any reason.
“These results support a hydroxyurea dosing strategy designed to produce fetal hemoglobin levels that exceed 20% in an effort to decrease hospitalization of children with sickle cell disease,” Dr Estepp said.
He and his colleagues are now conducting a multicenter trial to determine if toddlers with SCA would benefit from a similar dosing strategy or would respond better to a standard dose. 
Dosing of hydroxyurea (HU) in young patients with sickle cell anemia (SCA) should target a fetal hemoglobin (HbF) level above 20%, according to researchers.
Their study, HUSTLE, showed that children and adolescents who received a maximum tolerated dose (MTD) of HU were able to achieve HbF levels above 20%.
And patients who achieved such HbF levels had a significantly lower risk of hospitalization for any reason, including vaso-occlusive crisis, acute chest syndrome, and fever.
Jeremie Estepp, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these results in the American Journal of Hematology.
“Our analysis showed that, using this approach, hospitalizations for the average patient fell to less than 1 every couple of years rather than 4 to 6 annually,” Dr Estepp said. “This frees children from the fevers, pain, and other symptoms of this disease and gives them and their families more chances to enjoy childhood and adolescence.”
The study enrolled 230 SCA patients. Most had the HbSS genotype (n=214; 93%), although 7% (n=16) had HbSb0 thalassemia. The patients’ median age at HU initiation was 7.4 years (range, 6 months to 17.9 years). The mean HbF level at enrollment was 9.7%, and the median was 7.9% (range, 1.0-32.9%).
The researchers used a dose-escalation approach to determine the MTD of HU for each of the patients in this study. The MTD was defined by an absolute neutrophil count of 2000-4000 x 106/L or the presence of hematologic toxicity. The maximum absolute dose was 35 mg/kg/day or 2000 mg/day (whichever came first).
The mean daily dose of HU at the MTD was 26.7 mg/kg/day, and the median was 28.0 mg/kg/day (range, 13.0 to 35.0 mg/kg/day).
Three-quarters of patients (75.2%, 173/230) attained the MTD at the time of data censoring. Patients were followed for up to 4 years after study entry.
As far as treatment compliance, there were complete medication dispensation records available for 96% (220/230) of patients. And the patients were in possession of HU a mean of 93.6% of the time.
The researchers found that administering HU at the MTD resulted in a mean HbF of 26.7% and a median of 21.7% (interquartile range, 16.2% to 27.8%).
And the odds of being hospitalized were higher when a patient’s HbF level was less than 21%. The odds ratios for hospitalization were as follows:
- 4.1 for fever
- 2.6 for acute chest syndrome
- 2.2 for vaso-occlusive crisis
- 2.1 for any reason.
“These results support a hydroxyurea dosing strategy designed to produce fetal hemoglobin levels that exceed 20% in an effort to decrease hospitalization of children with sickle cell disease,” Dr Estepp said.
He and his colleagues are now conducting a multicenter trial to determine if toddlers with SCA would benefit from a similar dosing strategy or would respond better to a standard dose.
Dosing of hydroxyurea (HU) in young patients with sickle cell anemia (SCA) should target a fetal hemoglobin (HbF) level above 20%, according to researchers.
Their study, HUSTLE, showed that children and adolescents who received a maximum tolerated dose (MTD) of HU were able to achieve HbF levels above 20%.
And patients who achieved such HbF levels had a significantly lower risk of hospitalization for any reason, including vaso-occlusive crisis, acute chest syndrome, and fever.
Jeremie Estepp, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these results in the American Journal of Hematology.
“Our analysis showed that, using this approach, hospitalizations for the average patient fell to less than 1 every couple of years rather than 4 to 6 annually,” Dr Estepp said. “This frees children from the fevers, pain, and other symptoms of this disease and gives them and their families more chances to enjoy childhood and adolescence.”
The study enrolled 230 SCA patients. Most had the HbSS genotype (n=214; 93%), although 7% (n=16) had HbSb0 thalassemia. The patients’ median age at HU initiation was 7.4 years (range, 6 months to 17.9 years). The mean HbF level at enrollment was 9.7%, and the median was 7.9% (range, 1.0-32.9%).
The researchers used a dose-escalation approach to determine the MTD of HU for each of the patients in this study. The MTD was defined by an absolute neutrophil count of 2000-4000 x 106/L or the presence of hematologic toxicity. The maximum absolute dose was 35 mg/kg/day or 2000 mg/day (whichever came first).
The mean daily dose of HU at the MTD was 26.7 mg/kg/day, and the median was 28.0 mg/kg/day (range, 13.0 to 35.0 mg/kg/day).
Three-quarters of patients (75.2%, 173/230) attained the MTD at the time of data censoring. Patients were followed for up to 4 years after study entry.
As far as treatment compliance, there were complete medication dispensation records available for 96% (220/230) of patients. And the patients were in possession of HU a mean of 93.6% of the time.
The researchers found that administering HU at the MTD resulted in a mean HbF of 26.7% and a median of 21.7% (interquartile range, 16.2% to 27.8%).
And the odds of being hospitalized were higher when a patient’s HbF level was less than 21%. The odds ratios for hospitalization were as follows:
- 4.1 for fever
- 2.6 for acute chest syndrome
- 2.2 for vaso-occlusive crisis
- 2.1 for any reason.
“These results support a hydroxyurea dosing strategy designed to produce fetal hemoglobin levels that exceed 20% in an effort to decrease hospitalization of children with sickle cell disease,” Dr Estepp said.
He and his colleagues are now conducting a multicenter trial to determine if toddlers with SCA would benefit from a similar dosing strategy or would respond better to a standard dose.