REACHing Children With Sickle Cell Anemia in Sub-Saharan Africa

Daily treatment with hydroxyurea was feasible, well-tolerated, and safe for children with sickle cell anemia (SCA) living in sub-Saharan Africa, according to results from the Realizing Effectiveness Across Continents with Hydroxyurea (REACH) trial presented as a plenary abstract at the 2018 ASH Annual Meeting.

This is the largest prospective trial of hydroxyurea in this population, and “based on these data, we believe that wider access to hydroxyurea for SCA has the potential to save millions of lives in Africa,” lead study author Léon Tshilolo, MD, PhD, of the Centre Hospitalier Monkole in Kinshasa in the Democratic Republic of the Congo, said during his presentation.

Léon Tshilolo, MD, PhD, at the plenary session.

In December 2017, the U.S. Food and Drug Administration approved hydroxyurea to reduce the frequency of painful crises and the need for blood transfusions in pediatric patients (≥2 years) with SCA – marking the first approval of hydroxyurea in a pediatric population. However, because of hydroxyurea’s potential immunosuppressive effects, it was unclear whether the treatment would be safe and effective in children with SCA living in Africa, where coexisting conditions such as malaria and other infectious diseases are endemic, Dr. Tshilolo explained.

In the REACH trial, investigators evaluated the feasibility, safety, and benefits of hydroxyurea treatment in 635 children (age range = 1-10 years) who had been diagnosed with SCA and were treated at one of four sites in Angola, Democratic Republic of the Congo, Kenya, and Uganda.

Adherence was high among the study population, the researchers reported, and the overall retention rate was 94.2 percent at three years of follow-up.

After a median of 2.5 years of treatment, the average MTD across all sites was 22.5 mg/kg per day. Hematologic dose-limiting toxicities (the study’s primary safety endpoint) occurred in 5.1 percent of participants, “well below the protocol-specified 20 percent threshold,” Dr. Tshilolo said, adding that toxicity was similar between the screening period and the treatment phase.

After 12 months of hydroxyurea treatment, participants experienced improvements in several laboratory variables, including increases in hemoglobin (Hb), fetal Hb, and mean corpuscular volume and decreases in neutrophil, reticulocyte, and platelet counts (TABLE). These benefits were sustained through three-year follow-up. 

Improvements in laboratory parameters translated to clinical benefits for children who received hydroxyurea, the researchers reported. Compared with event rates at baseline, at three-year follow-up, incidence of all clinical adverse events (AEs) decreased from 308.4 to 170.7 events per 100 patient-years. The rate of sickle cell–related events also was reduced (from 114.5 to 53.0 events per 100 patient-years; p values not provided), including:

  • vaso-occlusive pain: 98.3 to 44.6 events per 100 patient-years
  • acute chest syndrome or pneumonia: 9.0 to 5.0 events per 100 patient-years

The data also alleviated concerns about infections in hydroxyurea-treated patients. Compared with baseline, during the treatment phase (though p values were not provided):

  • Rates of malaria infection dropped from 47.8 to 22.3 events per 100 patient-years
  • Rates of nonmalaria infection dropped from 142.5 to 90.0 events per 100 patient-years
  • Rates of severe, grade ≥3 infections dropped from 28.9 to 8.0 events per 100 patient-years

“Effects on all-cause mortality were also pronounced,” the authors added, “with 3.6 deaths per 100 patient-years during screening decreasing to 1.1 deaths per 100 patient-years on hydroxyurea [p value not provided].”

“Because of its positive impact on anemia, clinical events, and quality of life, hydroxyurea can now be considered for routine care of children with SCA in Africa,” Dr. Tshilolo concluded.

The study’s implications are limited by the single-arm design, and Dr. Tshilolo noted that the costs of hydroxyurea treatment and associated laboratory monitoring will be a major factor limiting more widespread use of the drug to treat SCA in Africa.

“The current cost of treatment is beyond the daily wage of most families living in sub-Saharan Africa,” he said. However, REACH participants received the hydroxyurea capsules, all lab tests, and transportation to clinic visits at no charge, which may have contributed to the high rates of retention and adherence to treatment on the study. “We hope that treatment will be made available to more patients through outside financial support, as is the case with treatment for HIV infection in several African countries.”

The authors report financial relationships with Addmedica, the manufacturers of hydroxyurea, and Bristol-Myers Squibb, which provided funding for the trial.


Tshilolo L, Tomlinson G, Williams TN, et al. Realizing effectiveness across continents with hydroxyurea (REACH): a prospective multi-national trial of hydroxyurea for sickle cell anemia in sub-Saharan Africa. Abstract #3. Presented at the 2018 ASH Annual Meeting, December 2, 2018; San Diego, CA.