Routine Serologic Duffy Testing in Pediatric Oncology: Clinical Utility and Feasibility in a Single‐Center Cohort

ABSTRACT Background Absolute neutrophil count (ANC) guides chemotherapy dosing, treatment timing, and clinical trial eligibility throughout pediatric oncology. Duffy‐null‐associated neutrophil count (DANC) is a physiologic variant characterized by lower ANC that may be misinterpreted as treatment‐related neutropenia. We evaluated the implementation and clinical impact of routine serologic Duffy antigen testing in a pediatric oncology program. Methods We conducted a retrospective observational study of pediatric oncology patients who underwent serologic Duffy antigen testing (Fya/Fyb phenotyping) at one institution between January 2023 and June 2026. Implementation outcomes included testing volume, laboratory workflow, turnaround time, and insurance reimbursement. Clinical utility was assessed by changes in interpretation of neutropenia or management following Duffy‐null identification. Duffy‐null patients were analyzed as an embedded case series. Results Sixty‐three patients underwent testing without additional laboratory infrastructure. Testing was integrated into the institutional blood bank workflow, with a 24–48 h turnaround and insurance coverage. Six patients with high‐risk B‐cell acute lymphoblastic leukemia (ALL), Down syndrome ALL, acute promyelocytic leukemia, Wilms tumor, pilocytic astrocytoma, and low‐grade glioma were identified as Duffy‐null. Before testing, these patients experienced chemotherapy delays, antimetabolite dose reductions or holds, prolonged diagnostic evaluation, or uncertainty regarding persistent neutropenia. Recognition of Duffy‐null status clarified interpretation of neutropenia and informed management. No infectious complications were observed following Duffy‐null identification. Conclusions Routine serologic Duffy testing was feasible within an existing pediatric oncology program and identified clinically meaningful Duffy‐null status across hematologic malignancies, central nervous system (CNS) tumors, and solid tumors. These findings support prospective multicenter evaluation of Duffy‐informed ANC interpretation, chemotherapy delivery, and clinical outcomes.