Phenotypic Remodeling and Functional Impairment of Circulating Neutrophils Are Associated with Infection-Related...

Infectious complications remain a leading cause of early mortality in patients with acute myeloid leukemia (AML), yet the contribution of qualitative neutrophil abnormalities to infectious risk remains poorly understood. We prospectively evaluated circulating neutrophil phenotypes and oxidative burst reserve in 27 consecutive patients with newly diagnosed AML treated at two tertiary referral centers. Neutrophil subsets were characterized by multiparameter flow cytometry according to CD16/CD62L expression and compared with those of healthy controls (n = 10) and AML patients in complete remission after induction therapy (n = 10). At diagnosis, patients exhibited expansion of activated-like N1 and immature N2B subsets, contraction of the predominant homeostatic N2A population, and impaired oxidative burst reserve (all p < 0.05). Both phenotypic abnormalities and oxidative burst partially recovered after 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 also demonstrated moderate discriminatory 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, higher log(N1/N2A) values were associated with lower oxidative burst reserve (Spearman r = -0.45; p = 0.018). These findings suggest that neutrophil phenotypic remodeling reflects innate immune dysfunction in AML and that the log-transformed N1/N2A ratio may serve as a practical biomarker for early identification of patients at increased risk of infection-related mortality.