Inpatient Burden and Outcomes of Neutropenic Fever in Cancer Patients: A Study Using the National Inpatient Database Sample from 2016- 2020
Authors: Gaddipati Greeshma , Mensah Boniface , Bilalaga Mariah Malak , Sainatham Chiranjeevi , Singh Tanmay , Singh Simardeep , Vasireddy Ramya , Ketineni Sujitha , Kancharla Pragnan , Mohebtash Mahsa 
Published: December 2024

Introduction
Neutropenic fever (NF) is a life-threatening condition defined by a single oral temperature ≥ 38.3°C or a temperature ≥ 38°C sustained for at least one hour, with an absolute neutrophil count &lt; 1,500 cells/microliter. Malignancies and chemotherapy both lead to bone marrow suppression, predisposing patients to NF. Current guidelines recommend inpatient management for a Multinational Association for Supportive Care in Cancer (MASCC) score of &lt; 21 and a Clinical Index of the Stable Febrile Neutropenia (CISNE) score of ≥3. However, prior studies have shown a significant inpatient burden for NF admissions, with a decreasing trend in NF mortality from about 14% in 2010 to 2% in 2013. Here, we explore the recent hospital burden and mortality of NF in cancer patients.
Methods
We utilized data from the National Inpatient Sample (NIS), the largest inpatient care database in the United States, between 2016 and 2020. All patients with neutropenia, febrile neutropenia, and neutropenia with fever as the admitting diagnoses were identified using ICD-10 codes. Only patients with a diagnosis of active cancer were included in the analysis. The primary outcome studied was mortality. Variables analyzed included demographics, types of malignancies, types of infections, overall outcomes, length of hospital stay, and total hospitalization costs. Statistical analysis was performed using STATA. Sampling weights were applied to generate nationally representative estimates.
Results
235,210 NF admissions in cancer patients were documented between 2016 and 2020. Of these, 50% were male, 65.5% were white, and 23% had a median income of less than $46,000. 19.6% were pediatric admissions. Private insurance was the highest payer for these patients (40.9%). Over 62% of patients were admitted to a large bed-sized hospital with 45.6% of admissions having a Charlson Comorbidity Index of 2. Hematologic malignancies (60.6%) had a higher incidence of NF than solid malignancies (39.4%). Acute lymphocytic leukemia (ALL) (26.8%) was the most common hematologic malignancy associated with NF followed by acute myeloid leukemia (23.5%) and non-Hodgkin's lymphoma (23.2%). Secondary malignancies (41.5%) were the most common solid malignancy associated with NF followed by breast cancer (12.1%), and gastrointestinal tumors (9.5%). A large proportion of the patients (78.1%) had no infection during their hospital stay. The most common source of infection was respiratory infections (10.6%) followed by gastrointestinal (4.2%), skin and soft tissue (3.6%), urinary (3.1%), and central nervous system infections (0.1%). Bacterial infections (11.4%) were the most common type of infection, followed by fungal (5.1%) and viral infections (2.6%), while protozoal infections were uncommon at 0.09%. The overall mortality of patients admitted with NF was 1.4%. The mean length of stay was 7.2 days, and the average total hospital cost was $81,335.
Conclusion
In our study, NF was observed more frequently in hematological malignancies, especially ALL. The most common causative agents of infection were bacterial, and respiratory infections carried a higher burden than other types. However, the low mortality rate in our study remains consistent with prior publications. Further studies are warranted to better assess the adherence to risk assessment scales such as MASCC and CISNE and to identify predictors of mortality in NF related hospitalizations to potentially reduce unnecessary hospitalizations and healthcare costs while improving patient outcomes.