Universal Duffy Testing is Likely Cost Effective for U.S. Population

Study establishes groundwork for understanding the cost-effectiveness of neutrophil testing

(SAN DIEGO, Dec. 7, 2024) — Universal testing for Duffy status for toddlers ages 9-12 months can be a potentially cost-effective intervention for the U.S. population, according to research presented at the 66th ASH Annual Meeting and Exposition.

The Duffy-null phenotype is commonly found among people with African and Middle Eastern genetic ancestry, affecting approximately two of three people in the United States with this self-identified race. People with the Duffy-null phenotype may have a lower absolute neutrophil count (ANC), or white blood cell count, which itself can be seen in the context of immunodeficiency, autoimmunity, or infection.

While those with Duffy-null associated neutrophil count (DANC) are not at increased risk of infection, they are often labeled as having neutropenia, a low white blood cell count, and this mis-labeling can lead to clinical trial exclusion, unnecessary changes to medication dosing, and unnecessary bone marrow biopsies. An estimated 10% of the U.S. population has the Duffy-null phenotype, and Duffy status can be assessed through a simple laboratory test to determine blood type, similar to how the Red Cross evaluates blood type during blood donations.

“I’ve been leading work to define Duffy reference ranges, but those ranges will have limited utility if people and their health care providers don’t know their Duffy status,” said Lauren Merz, MD, hematology fellow at Mass General Brigham and Dana-Farber Cancer Institute. “Obtaining Duffy status when toddlers are already getting tested for lead and hemoglobin gives parents the opportunity to learn their child’s status early and at a time where it’s not as overwhelming as the newborn phase.”

Dr. Merz and her colleagues assessed the cost-effectiveness of universal testing for Duffy status. They built a Markov cohort model that estimated the long-term costs and health benefits in the context of current clinical practice where diagnostic workup for neutropenia exists on a continuum from basic to extensive work-up.

A basic work-up included a referral to hematology and testing for anti-neutrophil antibodies, Duffy status, immunoglobulins (proteins that help fight infection), and fecal elastase or pancreatic amylase testing (to assess for certain immunodeficiencies). An extensive work-up includes basic testing plus nutritional, inflammatory, autoimmune, and HIV testing as well as congenital neutropenia (rare disorders which produce low levels of neutropenia) genetic testing, and a bone marrow biopsy.

The primary outcome of the study was the population-level incremental net monetary benefit (iNMB). This is a quantitative way to express the difference in health value derived (in $) from resources invested into pursuing universal Duffy testing versus that of what we currently do (i.e., no universal testing). In the context of basic diagnostic work-up, the iNMB was $15 million in favor of no universal testing [95% credible interval (CI), $5-24 million]. In the context of more expensive extensive diagnostic work-up, the iNMB was $133 million in favor of universal testing [95% CI, $96-174 million].

“We wanted to compare what a truly bare-bones assessment would look like compared to the most intense work-up,” said Dr. Merz. “In reality, most hematologists are somewhere in the middle, but we need to come to a formal consensus on what a standard neutropenia work-up looks like first. This study serves as the base for future, more nuanced analyses.”

The researchers systematically varied all parameters in the model to identify which parameters could change the conclusion of which strategy is the cost-effective strategy under each of the constraints of basic and extensive work-up. The only parameter that impacted the cost-effectiveness of universal testing was the prevalence of the Duffy null phenotype. This allowed the team to solve for a range threshold for Duffy null prevalence at which universal testing would be cost-effective under each constraint: needing at least 3% and 15% of the population to be Duffy null in the context of an extensive and basic neutropenia work-up, respectively.

A limitation of the study is that there are no neutropenia diagnosis guidelines, and the basic and full workups were informed by expert opinion. It also does not account for impact of Duffy status on access to clinical trials or certain critical medications like chemotherapy or treatments for autoimmune disease (these latter health benefits would accrue in favor of universal Duffy testing).

“Knowing your Duffy status is not the end of the story for a lot of people,” said Dr. Merz. “Understanding your Duffy status affects quality of life, affects the dosage of certain medications, and ultimately can affect your medical care.”

In the future, the researchers aim to come to a formal consensus on neutropenia testing and will build out a tiered system of testing to assess in the model. They also hope to examine the downstream ramifications of Duffy testing to understand the broader cost-benefits beyond the neutropenia work-up alone.

ASH is at the forefront of addressing a critical health equity concern through its groundbreaking initiative – the Reconsideration of Absolute Neutrophil Count (ANC) Reference Ranges by Duffy Status. The initiative is funded by a grant from the Doris Duke Foundation and seeks to ensure that all individuals, especially those with DANC, receive optimal care by redefining ANC reference ranges based on Duffy status. ASH aims to redefine ANC reference ranges and improve health care equity for all.

The American Society of Hematology (ASH) (hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. Since 1958, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology.

The Blood journals (https://ashpublications.org/journals) are the premier source for basic, translational, and clinical hematological research. The Blood journals publish more peer-reviewed hematology research than any other academic journals worldwide.

Melissa McGue, 202-552-4927
mmcgue@hematology.org