Hydroxyurea therapy improves lung function in children with sickle cell disease

Hydroxyurea therapy decreased the rate of annual decline in pulmonary function among children and young adults with sickle cell disease, according to results of a study presented at the American Thoracic Society International Conference.

“Persons with sickle cell disease experience an annual decline in lung function that starts in childhood,” Anya McLaren, MD, FRCP, MSc, respiratory medicine fellow at The Hospital for Sick Children in Toronto, said in a press release. “This study is the first of its kind to look at the effect of hydroxyurea on lung function. We found that hydroxyurea improved annual pulmonary function decline in children with sickle cell disease by more than one-third.”

Because hydroxyurea is known to decrease acute sickle-related events, such as pain and acute chest crises, McLaren and colleagues examined whether hydroxyurea therapy reduced the annual pulmonary function decline expected in children and young adults with sickle cell disease (SCD).

The analysis included data from 94 patients with SCD aged 6 to 20 years who received hydroxyurea therapy. Researchers conducted follow-up at 3, 6, 9, 12, 24, 36 and 48 months for complete blood count, hemoglobin F, liver and renal function test results.

Patients underwent pulmonary function tests — including FEV1, which measures the rate at which air moves out of the lungs, and FEF25-75, which determines the presence of an airway obstruction — a median of 3.68 years prior to initiation of therapy and a median of 3.84 years after therapy initiation.

At the initiation of hydroxyurea, the average patient age was 11 years (± 4.4), 96% had the HbSS genotype and 47% were male.

Before hydroxyurea initiation, the predicted rates of annual pulmonary decline were –1.98% for FEV1 (95% CI, –2.57 to –1.39) and –3.59% for FEF25-75 (95% CI, –4.43 to –2.57).

Rates of decline improved significantly following hydroxyurea initiation, to –1.28% for FEV1 (95% CI, –1.79 to –0.76) and –2.88% for FEF25-75 (95% CI, –3.49 to –2.28; P < 0.05 for both).

The changes in FEV1 and FEF25-75 occurred independently of patient age at the time of hydroxyurea initiation.

The safety and efficacy of hydroxyurea therapy for young people with SCD is known, but patient noncompliance remains an issue. Patient concerns regarding adverse events, especially carcinogenesis, remain the primary cause of underuse, according to McLaren.

“Long-term observational studies suggest beneficial effects without excessive damage to bone marrow, deleterious effects on growth and development, altered fertility, accumulation of mutations or increased carcinogenicity,” McLaren said. “Evidence that lung function may be better preserved while on hydroxyurea may encourage compliance and adherence to this medication for patients with sickle cell disease.” – by Nick Andrews

Reference:

McLaren A, et al. Abstract 6146. Presented at: ATS International Conference; May 13-18, 2016; San Francisco.

Disclos ure: HemOnc Today could not confirm the researchers' relevant financial disclosures at the time of reporting.