Early Treatment with Hydroxyurea Lessened SCD Severity Among Infants, Study Shows

Treatment with hydroxyurea since early infancy, starting at the age of one, is effective and safe at preventing sickle cell disease (SCD) complications, a follow-up study has found.

The study “Prospective longitudinal follow-up of children with sickle cell disease treated with hydroxyurea since infancy” was published in journal Pediatric Blood and Cancer.

Hydroxyurea is a medicine that increases the levels of fetal hemoglobin and lessens the symptoms of children and adults with SCD. When used as a long-term therapy, it also enhances patients’ survival.

In 2011, the Phase 3 BABY HUG clinical trial (NCT01783990) showed that hydroxurea resulted in significantly fewer disease-related complications and hospitalizations, compared to participants in a placebo control group.

Following those positive results, the Pediatric Sickle Cell Program of Northern Virginia implemented, in that same year, hydroxurea treatment for children with severe forms of the disease starting at 9-12 months of age. For children with severe disease the treatment was given at six months of age.

In this study, researchers followed up on the results — ranging from two to seven years — of children who began this therapy in 2011.

The initial dose of hydroxurea was of 20 to 25 milligrams per kilogram of body weight per day (mg/kg/day) and increased monthly until the maximum tolerated dose of 35 mg/kg/day.

In total, researchers analyzed data from 24 children, who started hydroxurea at age one and were at least two years old at the time of the analysis.

The analysis showed that the levels of hemoglobin were higher than those before they began treatment with hydroxurea in 87.5% of the cases. At the age of two or older, 71% of children kept constant levels of hemoglobin above 9 grams per deciliter (g/dL), and 52% kept that level above 10 g/dL.

At the time of the analysis, 62.5% of patients achieved a constant level of fetal hemoglobin above pre-treatment values. The average dose of hydroxurea was 22.6 mg/kg/d at age one, more than 25 mg/kg/d by age three, and up to 29 mg/kg/d by age 6.5.

“Starting HU early in life and maximizing HU [hydroxurea] dose prevented the age-dependent decline of HgbF [fetal hemoglobin], maintaining and sometimes superseding the pre-HU hemoglobin and HgbF levels up to age 7,” researchers wrote.

A total of 27 hospitalizations were recorded. These were more frequent among younger (less than 1-year-old) infants. In 70% of hospitalization cases, fever was the cause, followed by splenic sequestration (when a lot of sickled red blood cells become trapped in the spleen) (19%), and to other symptoms not related to SCD (7.4%).

Two patients required blood transfusions due to spleen problems. Annual exams to measure the speed of blood flow through the brain’s blood vessels showed no abnormal results in any of the patients.

“Results reported in this single-center observational study demonstrate that even in the community, outside of an academic research setting, implementation of HU [hydroxyurea] for children with SCD starting in infancy is very feasible and is highly effective in preventing disease complications,” the study concluded.

In 2014, a National Institutes of Health expert panel recommended hydroxyurea as a therapy for children with severe SCD. The recommendation is for the medicine to be given from the age of nine months, independent of symptoms‘ severity.