Researchers Drive Breakthroughs in Sickle Cell Care

Cincinnati Children’s researchers are helping to develop and present promising new options in sickle cell disease.

The researchers were involved in three studies that show significant progress in expanding the therapeutic options available for people with sickle cell disease—both in addressing unmet needs and in improving quality of life.

Currently, there are only a few available treatments for sickle cell disease, and many people who have the disease either can’t access them, can’t tolerate them or aren’t benefited by them.

The research results were presented at the American Society of Hematology annual meeting in December 2024.

Sickle Cell Meds Still Under-Prescribed

One study found that disease-modifying therapies for sickle cell disease remain significantly under-prescribed.

Using real-world data on disease-modifying therapy utilization from the American Society of Hematology Data Hub, which includes approximately 23,000 individuals with sickle cell disease, researchers found that only 24% have been prescribed one or more disease modifying therapies. Among patients with the most severe genotype, homozygous sickle cell anemia, or HbSS, who are candidates for disease modifying therapies, only 35% received therapy, underscoring a concerning gap in healthcare delivery.

Lead author of the study, Omar Niss, MD, director of classical hematology at Cincinnati Children’s, says, “Underuse of these therapies is a real problem. These medications help individuals with sickle cell disease daily by reducing pain, increasing hemoglobin levels, and in the long term by protecting their organs and improving their overall well-being.”

Despite their established benefits, the limited update of disease modifying therapies may reflect issues related to provider awareness, access to specialized care and disparities within the healthcare system. The researchers found a significant discrepancy in disease modifying therapy use by geographic location.

The researchers used electronic health records from 14 U.S. sites participating in the American Society of Hematology Data Hub to analyze data on 22,793 patients with all sickle cell disease genotypes between 2015 and 2023. The average age was 24 years, and 55% of the study cohort was female. Despite the limited use of disease modifying therapies overall, patients on hydroxyurea who achieved fetal hemoglobin levels of greater than 20%—a marker of therapeutic efficacy—demonstrated significant improvement in healthcare utilization and laboratory markers, underscoring the clinical value of appropriate disease modifying therapy use.

Efforts to address these prescribing gaps must focus on identifying and addressing barriers to effective use of these medications, Niss says. These should include improving education for both providers and patients, broader integration of sickle cell disease care into primary and community health settings and reducing structural barriers such as insurance limitations and geographic disparities. Promoting equitable access to comprehensive, guideline-based care is essential to improving clinical outcomes and reducing health disparities for people living with sickle cell disease.

Hydroxyurea May Help People with HbSC Form of Sickle Cell Disease

A second study found that hydroxyurea may help more people with sickle cell disease than once thought.

Hydroxyurea, which induces fetal hemoglobin to prevent sickling, is already the standard of care for the most common form of sickle cell disease, hemoglobin SS. Russell Ware, MD, PhD, director of hematology and a leading sickle cell disease researcher at Cincinnati Children’s, served as corresponding author on a phase II clinical trial that evaluated whether hydroxyurea could also help people with the hemoglobin SC variant of the disease.

Called the PIVOT trial, the study was performed in Ghana, where close to 50% of people with sickle cell disease have the hemoglobin SC variant. That’s compared to the United States, where the figure is between 25% and 30%.

Both children and adults enrolled in the PIVOT trial experienced significant improvements in several laboratory measures of sickle cell disease severity, including a higher volume of larger red blood cells—which are less likely to become sickle-shaped, higher fetal hemoglobin levels, and lower leukocyte and neutrophil counts. Drug toxicities were mild and expected.

Both children and adult participants also experienced reductions in the rate of vaso-occlusive crises and hospitalizations compared to those on placebo. A larger phase III trial is warranted to confirm these encouraging results, Ware says.

Hydroxyurea Pharmacokinetics in Children with Sickle Cell Anemia

Alexandra Power-Hays, MD, a pediatric hematologist who leads the multidisciplinary sickle cell team in the Cincinnati Children’s Health Equity Network, served as lead author for another study that compared pharmacokinetic parameters of hydroxyurea in children with sickle cell anemia who live in Africa and the Caribbean compared to those in America. The goal was to determine whether a maximum-tolerated dose could be standardized.

For sickle cell anemia, the hydroxyurea maximum-tolerated dose is the dose that optimizes protective fetal hemoglobin induction without excess toxicity. A study at Cincinnati Children’s demonstrated that early treatment of children on hydroxyurea maximum-tolerated dose can achieve and sustain fetal hemoglobin levels targeted in sickle cell gene therapy.

A partnership between the divisions of hematology and clinical pharmacology at Cincinnati Children’s had previously developed a hydroxyurea pharmacokinetic model for American children with sickle cell anemia. Power-Hays and her fellow researchers then wanted to compare global cohorts to determine if the model they developed was safe to use in other populations, where resources, environments and genetics differ. This is critical because the majority of the 7 million people living with sickle cell anemia live in low- and middle-income countries.

The study found that the doses recommended to achieve maximum-tolerated dose were remarkably similar across global regions. The researchers concluded that hydroxyurea pharmacokinetic parameters of children with sickle cell anemia from around the world are consistent in absorption, volume of distribution, clearance, dose predicted to reach maximum-tolerated dose, and hydroxyurea exposure at maximum-tolerated dose.

The researchers observed: “Future trials will evaluate the feasibility, safety, benefits and cost-effectiveness of prospective pharmacokinetic-guided hydroxyurea dosing in Africa and the Caribbean. Pharmacokinetic-guided dosing may allow more children to be treated with hydroxyurea at maximum-tolerated dose upfront, maximizing the benefits of this lifesaving medication without stepwise escalation.”

Ongoing innovation, such as pharmacokinetic-guided dosing, is necessary to optimize the benefits of this safe, affordable medication in the places with the highest burden of sickle cell anemia, Power-Hays says.

(Published December 2025)

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