Children with sickle cell anaemia can safely take oral hydroxyurea at maximum tolerated doses without facing a higher risk of infections, according to new research published in The Lancet Haematology and backed by a decade-long international trial.
Roughly 550,000 children are born with the condition annually, facing complications like pain, vulnerability to infections and chronic ill health, including life-threatening bacterial and viral infections. Sickle cell anaemia stands as the most severe and common inherited blood disease in humans, with approximately 80% of all cases located in sub-Saharan Africa. To combat these risks, doctors rely on hydroxyurea, a medication that prompts the body to produce fetal haemoglobin. This form of haemoglobin stops red blood cells from taking on the rigid sickle shape.
Ten-Year REACH Trial Results Across Four African Nations
Because the drug dampens the immune system, medical teams worried it could heighten infection risks where clinical resources remain scarce. While high-income countries treat hydroxyurea as a standard therapy, physicians in low-income settings have historically exercised caution. To test that theory, researchers launched a trial across Angola, DR Congo, Kenya, and Uganda as part of the National Institutes of Health-funded Realizing Effectiveness Across Continents with Hydroxyurea initiative, known as the REACH trial.
The study involved 606 children and young adults living with sickle cell anaemia. Over more than 10 years of treatment, the data disproved early fears. Researchers discovered no increase in either the incidence or severity of infections, including malaria, among children taking the drug.
Over 10-years of treatment, the incidence and severity of infections did not increase, and in many cases, were decreased.
The trial showed that the risk of illness actually dropped. The data revealed a 51% drop in malaria risk and a 38% decrease in non-malarial infections.
Global Standard of Care Findings
Professor Tom Williams is study lead at Imperial’s Centre of African Research and Engagement and the Institute of Global Health Innovation. Professor Williams pointed out that the scale of the observation period removes lingering doubts about immune suppression in vulnerable environments. The findings mark a change for pediatric care in resource-limited regions, offering clinical data to reassure hesitant physicians.
Funding for the research came from the National Heart, Lung, and Blood Institute alongside the Cincinnati Children’s Research Foundation, with additional backing for Professor Williams from the Wellcome Trust. With a full decade of safety data now published, investigators recommend that children with sickle cell anaemia living in low-resource settings receive treatment with hydroxyurea at the maximum tolerated dose.
Evaluating Combination Therapy With Chronic Transfusions
Chronic transfusions are usually reserved for treatment escalation and offered to patients with more severe disease, especially for stroke prevention, but they carry drawbacks like iron overload and alloimmunization. Beyond hydroxyurea monotherapy, researchers are also studying how the drug performs when paired with chronic blood transfusions for patients suffering from severe disease. Professor Tom Williams, study lead at Imperial’s Centre of African Research and Engagement and the Institute of Global Health Innovation, pointed out that the scale of the observation period removes lingering doubts about immune suppression in vulnerable environments. A prospective phase 2 clinical trial led by Nickel and colleagues evaluated fourteen participants aged 2 to 25 who had relied on transfusion therapy for over a year.
Nickel and colleagues evaluated fourteen participants aged 2 to 25 who had relied on transfusion therapy for over a year, exploring the safety of layering hydroxyurea on top of ongoing regimens.
Nine of those participants successfully completed a year of combination therapy. The results demonstrated a reduction in blood transfusion volume—over 10 mL/kg/year—compared to previous transfusion-only therapies. Investigators noted that combining the treatments appeared to enhance adherence to hydroxyurea while increasing levels of fetal haemoglobin.
Our findings indicate that combining hydroxyurea with transfusions is a feasible approach for some patients, potentially leading to reduced transfusion requirements and better health outcomes.
The combination approach resulted in higher pre-transfusion hemoglobin S levels among participants, suggesting that increased hemoglobin S could potentially lead to worsening cerebrovascular complications over time. Despite the encouraging drop in transfusion burdens, clinical challenges remain.