Neutropenia and Duffy-null associated neutrophil count

Condition

People with the Duffy-null phenotype [those who lack the Duffy a (Fy^a) and b (Fy^b) antigens on their red blood cells] are more likely to have lower neutrophil counts than would be expected based on standard neutrophil reference ranges. This phenomenon is due to the important role the Duffy antigen plays in neutrophil trafficking; without the Duffy antigen, neutrophils are preferential localized to the spleen with fewer circulating in peripheral blood (Permanyer et al., Cell Mol Immunol., 2017). Duffy-null phenotype is present in two-thirds of individuals of African ancestry, and ~20% of people of Middle Eastern Descent, but only in <1% of people of European descent.

Duffy-null associated neutrophil count is a normal variant. Healthy individuals with Duffy-null phenotype generate appropriate neutrophil number and function in response to infection, stress, or granulocyte-colony stimulating factor (G-CSF), without having an increased risk of infection or bone marrow pathology(Legge et al, Hum Mol Genet 2020; Van Driest et al., JAMA Internal Medicine 2021; Merz et al., Blood Advances 2023; Hysong et al., Blood Advances 2025). Historically, Duffy-null individuals were diagnosed or labeled as having ‘benign ethnic neutropenia’. This phrasing is no longer recommended, as it suggests this common phenotype in specific ancestral populations is abnormal (Merz & Achebe, Blood 2021).

Guidance at RECRUITMENT

ACCEPT

Guidance at CT/WORK-UP

If isolated neutropenia in an otherwise healthy individual:

Test for Duffy status. If Duffy-null phenotype, eligible for donation. Else, workup the donor for isolated neutropenia as appropriate.

If a donor has Duffy-null phenotype:

Accept

If the donor is of African or Middle Eastern Heritage:

If feasible, donor centers can consider screening for Duffy status.

If known, the Duffy status of the donor should be reported to the transplant center.

Individual at Risk

Donor

Justification for guidance

The American Academic of Family Physicians, American Society for Clinical Pathology and American Society for Clinical Laboratory Science developed Choosing Wisely Recommendations (aafp.org/pubs/afp/collections/choosing-wisely/526.html) outlining that, in healthy individuals of African or Middle Eastern descent who have isolated neutropenia based on standard laboratory reference ranges, further workup should not be performed without first testing for Duffy-null phenotype. The recommendations further stipulate that asymptomatic individuals with Duffy-null associated neutrophil count do not require further investigations and should not be deferred from clinical care solely due to their absolute neutrophil counts. These recommendations were based on multiple series showing that Duffy-null phenotype is not associated with bone marrow pathology and can lead to unnecessary marrow biopsies (e.g. Van Driest et al., JAMA Internal Medicine 2021).

Based on this guidance, potential donors with Duffy-null phenotype should be permitted to donate if otherwise healthy, without further investigation for their lower absolute neutrophil counts than would be expected based on standard reference ranges. For healthy potential donors with isolated neutropenia, knowledge that those donors are Duffy-null provides helpful reassurance and will help to avoid unnecessary testing (eg bone marrow biopsies).

Additionally, if feasible, donor centers can consider screening potential donors for Duffy status if they are of African or Middle Eastern heritage, as the identification of Duffy-null phenotype in a donor could have potential implications for recipient care/ monitoring. In a retrospective series of 189 patients with Duffy testing available who had received BCMA-directed CAR-T for multiple myeloma (Avigan et al., Blood Advances 2025), patients with Duffy-null phenotype (n=28) had delayed neutrophil engraftment, as well as increased incidence of viral upper respiratory tract infections which did not require treatment, but otherwise had similar incidence of infections within the first 100 days post-CAR-T. These data highlight one example of the potential relevance of how knowledge of the donor’s Duffy status can impact on recipient care. Knowledge of the donor’s (and therefore the recipient’s) Duffy status could also impact on eligibility assessments for medications known to cause neutropenia (e.g. sulfamethoxazole/trimethoprim for Pneumocystis jirovecii Pneumonia Prophylaxis), post-transplant maintenance therapy, or clinical trials (Hibbs et al., JAMA Network Open 2024). For these reasons, if known, the Duffy status of the donor should be reported to the transplant center. For allograft recipients who receive a graft from donor of African or Middle Eastern descent whose Duffy status is not known, transplant centers may consider recipient Duffy genotyping following engraftment.

References

Version	Published	Changed By	Comment
CURRENT (v. 1)	Oct 28, 2025 12:59	Eefke van Eerden

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