Increasing Hydroxyurea Dose in Young Patients With Sickle Cell Anaemia Reduces Hospitalisations

November 10, 2017

MEMPHIS, Tenn -- November 10, 2017 -- Using hydroxyurea to boost average fetal haemoglobin levels above 20% in children and teenagers with sickle cell anaemia was associated with at least a 2-fold reduction in hospitalisation for any reason, according to a study published in the American Journal of Hematology.

The findings should help settle the debate about how to optimise hydroxyurea for treatment of sickle cell disease in young people.

Rather than calculating a standard dose of hydroxyurea based on patient’s weight, researchers used a dose-escalation approach to determine the maximum tolerated dose for each of the 230 patients enrolled in the study.

“Our analysis showed that using this approach, hospitalisations for the average patient fell to less than 1 every couple of years rather than 4 to 6 annually,” said lead author Jeremie Estepp, MD, Department of Hematology, St. Jude Children’s Research Hospital, Memphis, Tennessee. “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.”

Despite the proven benefits of hydroxyurea, the optimal dosing strategy for the drug has remained controversial. Also lacking has been evidence of overall improved patient outcomes if hydroxyurea is used to increase blood levels of fetal haemoglobin to more than 20%.

For the current study, patients received a starting dose of hydroxyurea that was escalated in a stepwise manner until patients reached a predetermined maximum dose (either 35 mg/kg/day or 2,000 mg/day) or experienced mild neutropenia. About 2% of patients in this study developed transitory neutropenia. More than 75% of patients had completed the dose escalation when study data were analysed.

More than half the patients received a hydroxyurea starting dose of 20 mg/kg. The average dose was 27 mg/kg/day when the dose escalation process ended and ranged among patients from 13 to 35 mg/kg/day.

Pharmaceutical records suggest that patient compliance was good. Throughout the 4-year study, almost 94% of patients had possession of their medication, which exceeded the national average.

“St. Jude has invested in the clinical infrastructure, including case managers and other staff to support and follow up with families to make sure they receive recommended care, including medication,” said Dr. Estepp. “These results show how patients and families benefit.”

Average fetal haemoglobin levels in patients increased from 9.7% prior to treatment to 21.7% -- a level that was sustained for the 4 years covered in this analysis. Overall, 60% of study patients attained fetal haemoglobin levels of more than 20%.

The odds of being hospitalised for pain or any reason were about doubled for patients with fetal haemoglobin levels of 20% or less. The lower level was also associated with 2.6-times greater odds of hospitalisation for acute chest syndrome and about 4-times greater odds of being hospitalised for fever.

“These results support a hydroxyurea dosing strategy designed to produce fetal haemoglobin levels that exceed 20% in an effort to decrease hospitalisation of children with sickle cell disease,” said Dr. Estepp.

The researchers are now leading a multicentre trial to determine if toddlers with sickle cell disease would benefit from a similar dosing strategy or would respond better to a standard dose.

Reference: http://dx.doi.org/10.1002/ajh.24906

SOURCE: St. Jude Children’s Research Hospital

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