Phenotypic Remodeling and Functional Impairment of Circulating Neutrophils Are Associated With Infection-related Mortality in Acute Myeloid Leukemia
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Infection remains a major cause of early mortality in patients with acute myeloid leukemia (AML). Although prolonged neutropenia is a well-established risk factor, qualitative abnormalities of circulating neutrophils may also contribute to infectious susceptibility. We investigated whether neutrophil phenotypic remodeling and impaired oxidative burst are associated with infection-related mortality in AML. Methods Twenty-seven consecutive patients with newly diagnosed AML were prospectively enrolled at two tertiary referral centers. Circulating neutrophil subsets were characterized by multiparameter flow cytometry according to CD16/CD62L expression as N1 (CD16^high^/CD62L^dim^), N2A (CD16^high^/CD62L^high^), N2B (CD16^dim^/CD62L^high^), and N2C (CD16^dim^/CD62L^dim^). Healthy controls (n = 10) and AML patients in complete remission after induction therapy (n = 10) served as comparison groups. Neutrophil oxidative burst reserve was assessed using the nitroblue tetrazolium reduction assay. Logistic regression, receiver operating characteristic (ROC), and Kaplan–Meier analyses were used to evaluate the prognostic value of the log-transformed N1/N2A ratio. Results Newly diagnosed AML was characterized by expansion of N1 and N2B neutrophils, contraction of the predominant N2A subset, and impaired oxidative burst reserve (all P < 0.05). Both neutrophil phenotype and oxidative burst partially normalized following induction therapy. Infection-related mortality occurred in 22.2% of patients. After adjustment for age, the log-transformed N1/N2A ratio remained independently associated with infection-related mortality (adjusted OR 4.90, 95% CI 1.17–20.49; P = 0.029). The ratio showed moderate discriminative performance (AUC 0.774, 95% CI 0.585–0.963; P = 0.049), and the optimal cutoff (−2.022) identified patients with significantly inferior infection-related survival (HR 12.83, 95% CI 2.62–62.90; log-rank P = 0.0017). In addition, the log(N1/N2A) ratio correlated inversely with oxidative burst reserve (Spearman r = −0.45; P = 0.018). Conclusions AML is associated with coordinated neutrophil phenotypic remodeling and impaired oxidative burst. The log-transformed N1/N2A ratio was independently associated with infection-related mortality, correlated with neutrophil functional impairment, and identified patients with inferior infection-related survival. These findings suggest that neutrophil phenotyping may represent a useful biomarker for early assessment of infectious risk in AML and warrant validation in larger prospective cohorts.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223105181