Beyond Febrile Neutropenia: Reframing Neutropenic Infection as a Clinical Spectrum in Oncology—A Narrative Review and Conceptual Framework

Background: Febrile neutropenia is a critical emergency construct, but infection and sepsis can occur without fever. Objective: To examine the clinical evidence of nonfebrile neutropenic infection, potential mechanisms of an attenuated febrile response, physiological body-temperature variation, and limitations of clinical thermometry. Methods: A narrative review was supplemented by a targeted, transparently documented three-domain evidence map of published systematic syntheses, thermometry-accuracy studies, and oncology-neutropenia cohorts, updated on 1 November 2026. No new exhaustive systematic review or meta-analysis was performed. Results: A synthesis of 36 studies (7636 healthy adults) reported site-specific oral and rectal temperature distributions of 35.73–37.41 °C and 36.32–37.76 °C (mean ± 2 SD), which do not establish a universal core-temperature interval. Peripheral and oral thermometers demonstrated pooled fever-detection sensitivities of 0.64 and 0.53, respectively, in non-neutropenia-specific populations. Nonfebrile infection proportions included 9/69 (13.0%) severe ICU infection episodes and 70/186 (37.6%) bloodstream infections without a recorded temperature ≥ 38.0 °C in a separate oncology-neutropenia cohort; an additional post-transplant corticosteroid cohort is discussed separately. These denominators do not permit a meaningful pooled incidence of afebrile neutropenic sepsis. Conclusions: Fever-based clinical pathways remain essential, but suspected infection, physiological deterioration, and organ dysfunction warrant evaluation irrespective of temperature.