Hematologic malignancies to define a distinct high-risk sepsis phenotype among hospitalized cancer patients.

Abstract

e23245 Background: Sepsis is a leading cause of mortality among hospitalized cancer patients. Although cancer is broadly recognized as high risk, patients with hematologic malignancies are often treated as biologically uniform. We hypothesized that hematologic malignancies define a distinct high-risk sepsis phenotype and that mortality risk varies across subtypes. Methods: We performed a retrospective cohort study of adult hospitalized cancer patients with sepsis using a national inpatient database. Demographics, comorbidities, acute organ dysfunction, malignancy subtype, and hospital characteristics were extracted. Multivariable logistic regression identified factors independently associated with in-hospital mortality. Hematologic malignancies were first analyzed as a group relative to solid tumors. Subtype-specific analyses were performed for AML, ALL, CLL, CML, and MM, with odds of mortality calculated for each subtype compared with other hematologic malignancies. Models were adjusted a priori for age, sex, Charlson Comorbidity Index, cancer stage, septic shock, and hospital characteristics including elective status and region. Results: The cohort included 338,545 hospitalizations, with 62,830 deaths (18.6%). After adjustment, hematologic malignancy remained independently associated with increased in-hospital mortality (OR 1.21, 95% CI 1.15–1.28; p < 0.001), whereas solid tumors were not (OR 0.82, 95% CI 0.78–0.87; p < 0.001), supporting hematologic malignancy as a distinct high-risk sepsis phenotype. Acute organ failure was the dominant mortality driver, including acute respiratory failure (OR 5.29, 95% CI 5.07–5.52; p < 0.001) and dialysis-requiring acute kidney injury (OR 2.87, 95% CI 2.65–3.11; p < 0.001). Venous thromboembolism (OR 1.53, 95% CI 1.43–1.65; p < 0.001) and opioid use disorder (OR 1.36, 95% CI 1.14–1.64; p = 0.001) were also associated with mortality. Within hematologic malignancies, risk varied substantially. AML was associated with higher mortality (OR 1.82, 95% CI 1.75–1.91; p < 0.0001), while CLL showed a modest increase (OR 1.08, 95% CI 1.03–1.14; p = 0.003). In contrast, ALL (OR 0.76, 95% CI 0.70–0.83), MM (OR 0.81, 95% CI 0.78–0.85), and CML (OR 0.91, 95% CI 0.82–1.01) were associated with lower or neutral risk. These findings identify AML as the principal driver of excess sepsis mortality among hematologic cancers. Conclusions: Hematologic malignancies represent a distinct high-risk sepsis population, but they are not biologically uniform. AML defines a particularly high-risk sepsis phenotype, while ALL, MM, and CML show lower mortality risk. These findings support disease-specific risk stratification, early critical-care engagement, and tailored sepsis pathways, particularly for AML.