Inpatient Burden and Clinical Outcomes of Febrile Neutropenia in Cancer Patients: A National Inpatient Sample Database Analysis

Introduction: Febrile neutropenia is a serious and common complication that can arise in patients diagnosed with hematopoietic cancers or those receiving chemotherapy. Damage to the bone marrow, either drug-induced or due to malignancy, can lead to inefficient production of white blood cells, including neutrophils. Patients with this immunocompromised state are at a greater risk to contracting a life-threatening infection. This study evaluates the prevalence and subsequent clinical outcomes of febrile neutropenia in hospitalized patients diagnosed with cancer.

Methods: Hospitalizations for febrile neutropenia/fever and neutropenia (F&N) as the primary reason for admission (principal diagnosis) were identified using ICD-10 coding from the 2019 National Inpatient Sample (NIS). The NIS is the largest all-payer inpatient database in the US. Only F&N patients with a co-diagnosis of cancer (identified using the Clinical Classifications Software (CCS) coding) were included in this study. The All Patient Refined Diagnostic Related Groups (APR-DRG) severity index was used to identify the overall severity of illness subclass and the risk of mortality within each diagnoses related group, classifying the admissions as either mild, moderate, major, or extreme loss of function. Sampling weights were applied to generate nationally representative estimates.

Results: In 2019, there were 118,965 hospitalizations that had F&N as one of the listed diagnoses. Of these, 27,735 (23.3%) had febrile neutropenia coded as the primary admission diagnosis. 88.1% of these admissions with a primary admitting diagnosis of neutropenia simultaneously had a co-diagnosis of cancer per CCS coding (n=24,444) and were included in the final analysis. Of these, 24.5% (n=5,995/24,444) were pediatric admissions (<18 years. The majority of cancer patients with febrile neutropenia (57.2%) were categorized as Moderate severity when measured by the APR-DRG severity index and were treated at teaching hospitals (86.0%) and those with large bed sizes (>500 beds (59.8%).

Of all the cancer types, those with hematologic malignancies had the highest incidence (59.4%), followed by secondary malignancies (16.3%), breast cancer (7.8%), bone and soft tissue cancers (6.6%), and gastrointestinal cancer (5.0%). Among the hematologic malignancies, the distribution was as follows: 25.2% non-Hodgkin lymphoma (NHL), 24.4% acute myeloblastic leukemia (AML), 24.1% acute lymphoblastic leukemia (ALL), 11.3% myelodysplastic syndrome (MDS) and 7.2% multiple myeloma (MM). Among pediatric patients with F&N, ALL was the most common malignancy (44.0%) followed by bone and soft tissue cancers (16.7%).

Of all admissions with primary diagnosis of F&N, 24% received at least one type of blood transfusion (red blood cells (RBCs), platelets, or plasma): 21.7% received RBC transfusions, 12.5% platelet, and 0.3% received plasma during the hospitalization.

Overall, 1.0% of all cancer admissions with a primary admitting diagnosis of febrile neutropenia resulted in death during hospitalization (n=255). Of these deaths, 74.5% had a hematologic malignancy, 66.7% were over the age of 65, and 70.6% were of the extreme severity of illness class. Compared to the average length of stay in all hospitalizations with febrile neutropenia with a co-diagnosis of cancer, those who died during hospitalization had a significantly longer length of stay (12.9 vs. 4.3 days; p<0.001). The overall median hospital charges of a F&N-related admission was $55,812. Hospitalization resulting in deaths had 4 times the hospital charges as compared to those who did not die during hospitalization ($230,601 vs. $53,963, respectively; p<0.001).

Conclusion: This study represents the inpatient burden of hospitalizations with a primary admitting diagnosis of febrile neutropenia, specifically in those diagnosed with cancer. Febrile neutropenia cases were seen mostly in patients with hematologic malignancies – more commonly seen amongst adults with NHL or AML and pediatric hospitalizations with ALL. There was a 1% all cause mortality in these hospitalizations, which most likely represented those with significantly. higher severity of illness, longer length of stay, and higher hospital charges. Febrile neutropenia represents a significant healthcare burden in pediatric and adult hospitalizations with cancer.