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Hydroxyurea therapy feasible for primary stroke prevention in Nigerian children with sickle cell anemia
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SAN DIEGO — Treatment with moderate doses of hydroxyurea for primary stroke prevention appeared feasible for Nigerian children with sickle cell anemia who had elevated transcranial Doppler measurements, according to study results presented at the ASH Annual Meeting and Exposition.
Researchers reported high rates of successful recruitment, retention and treatment adherence, and they observed no evidence of excessive toxicity among hydroxyurea-treated children compared with those who did not receive treatment.
Nigeria has the largest sickle cell disease burden in the world. An estimated 150,000 children there are born with sickle cell disease each year. By comparison, 2,400 children in the United States and 300 children in the United Kingdom are born with sickle cell disease each year.
Routine use of transcranial Doppler measurements and regular blood transfusion therapy for those with velocities greater than 200 cm/second have considerably reduced the rate of strokes among children with sickle cell anemia.
“Regular blood transfusion therapy is not a viable option for children [in sub-Saharan Africa] with sickle cell anemia due to inadequate blood supply, cost of monthly blood transfusions [and] unsafe transfusion practices with high probability of blood-borne infections,” Najibah Aliyu Galadanci, MBBS, MPH, of the department of hematology at Bayero University and Aminu Kano Teaching Hospital in Nigeria, said during a press conference.
Galadanci and colleagues conducted a single-site, single-arm trial to assess the feasibility of hydroxyurea therapy for primary stroke prevention in children in Nigeria with sickle cell anemia.
All participants were aged 5 to 12 years and attended the pediatric sickle cell disease clinic at Aminu Kano Teaching Hospital.
The acceptability of hydroxyurea therapy to families — determined based on recruitment rate, retention rate and adherence to study medication — and preliminary evidence of hydroxyurea safety served as the primary objectives.
All study participants underwent screening with transcranial Doppler to determine elevated stroke risk, defined as time-averaged maximum velocity of at least 200 cm/second in the middle cerebral artery.
Twenty-five children found to have transcranial Doppler velocity of 200 cm/second or greater received moderate-dose hydroxyurea therapy — 20 mg/kg per day — for 3 years.
Another 210 participants who had transcranial Doppler velocities less than 200 cm/second agreed to be followed prospectively in a comparison group.
Patients in the treatment group were slightly older (median age, 8 years vs. 6.8 years), but there were no statistically significant differences between groups with regard to age, sex, height, weight or ethnicity.
Median time on therapy was 2.1 years (range, 0 to 2.8), and average mean cell volume increased from 85 fL at baseline to 101.3 fL at 2 years.
All participants in the treatment group attended monthly research visits (total, n = 603). No participants voluntarily dropped from the trial, but one was withdrawn due to progressive renal failure.
Median transcranial Doppler velocity among those who underwent hydroxyurea therapy declined from 211 at baseline (n = 27) to 165 at 24 months (n = 25).
After median follow-up of 2 years, no strokes occurred in the treatment group and one occurred in the comparison group.
The hospitalization rate was lower in the treatment group than the comparison group (35.1 per 100 patient-years vs. 48 per 100 patient years).
Nine deaths occurred. One patient in the treatment group died after withdrawal due to progressive renal disease, and eight participants in the comparison group died.
No participants who died received PCV-13 vaccinations, and two received Haemophilus influenza type B vaccinations. At the time of death, all participants had been prescribed malaria prophylaxis, and all but one had been prescribed penicillin prophylaxis.
“We have shown that a moderate dose of hydroxyurea does not cause adverse effects and may be effective for stroke prevention,” Galadanci said in a press release.
The results “provide strong preliminary evidence” to support an ongoing randomized phase 3 trial designed to compare two doses of hydroxyurea — 20 mg/kg per day vs. 10 mg/kg day — for stroke prevention in 200 children in Nigeria with sickle cell anemia. Results of that trial are expected in 2021. – by Mark Leiser
Reference: Galadanci NA, et al. Abstract 122. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Disclosure: The researchers report no relevant financial disclosures.