Understanding What is a Neutropenic Fever Classification?

October 1, 2025 •

2 min read

Approximately 13% to 21% of patients with solid tumors receiving myelosuppressive chemotherapy will experience febrile neutropenia. A crucial aspect of managing this condition involves understanding what is a neutropenic fever classification, which helps determine the appropriate level of care and treatment plan.

Quick Summary

Neutropenic fever classification involves stratifying patients into high-risk or low-risk categories using clinical assessment tools like the MASCC or CISNE scores. This determines management, including outpatient care versus hospitalization and the type of antibiotic therapy.

Key Points

Definition: Neutropenic fever is defined by a fever and an absolute neutrophil count (ANC) below a certain threshold, typically <500 cells/µL.
Risk Stratification: Patients are classified into high-risk or low-risk categories based on their likelihood of serious complications, guiding treatment decisions.
MASCC Score: The Multinational Association for Supportive Care in Cancer (MASCC) score uses clinical factors to identify low-risk patients (score ≥ 21) who may be candidates for outpatient management.
CISNE Score: The Clinical Index of Stable Febrile Neutropenia (CISNE) score is used for stable outpatients with solid tumors, offering a more granular risk assessment than MASCC.
Infection Documentation: A separate classification system categorizes cases as microbiologically documented, clinically documented, or unexplained fever based on the identification of a pathogen or infection site.
Treatment Implications: High-risk patients typically require hospitalization and intravenous antibiotics, while some low-risk patients may be managed as outpatients with oral antibiotics.

Defining Neutropenic Fever

Neutropenic fever is a serious medical condition defined by a fever and a low absolute neutrophil count (ANC). Neutrophils are white blood cells that fight infection. The Infectious Diseases Society of America defines it as a single oral temperature ≥38.3°C (101°F) or ≥38.0°C (100.4°F) sustained for over an hour, with an ANC below 500 cells/µL, or an ANC below 1,000 cells/µL expected to fall below 500 cells/µL within 48 hours. This is common in chemotherapy patients due to bone marrow suppression.

The Purpose of Classification

Immediate risk assessment is vital due to the high risk of serious infection, sepsis, and death. Classifying neutropenic fever groups patients by their likelihood of severe complications, guiding decisions on care setting (inpatient vs. outpatient) and antibiotic therapy. Validated risk assessment tools formalize this process.

Risk-Stratification Tools

The MASCC risk index and the CISNE score are two commonly used tools for classifying neutropenic fever based on clinical factors.

The MASCC Score

The MASCC risk index helps identify low-risk patients potentially suitable for outpatient management. A score of 21 or greater (out of a maximum 26 points) indicates low risk, while a score below 21 signifies high risk. The criteria include burden of illness, hypotension, COPD, tumor type, outpatient status, hydration, and age.

The CISNE Score

The CISNE score is designed for stable outpatients with solid tumors. It uses six variables to categorize patients into low, intermediate, and high-risk groups for serious complications. These variables include ECOG performance status, COPD, stress-induced hyperglycemia, chronic cardiovascular disease, monocyte count (<200 per mcL), and mucositis grade (≥2).

Comparison of MASCC and CISNE Scores


Feature	MASCC Score	CISNE Score
Patient Population	Validated for both hematologic and solid tumor patients	Designed for stable outpatients with solid tumors
Risk Grouping	Dichotomous (High or Low)	Tripartite (High, Moderate, Low)
Scoring Range	0 to 26 points	0 to 8 points
Thresholds	≥ 21 points = Low-risk; < 21 points = High-risk	0 points = Low-risk; 1-2 points = Intermediate-risk; ≥ 3 points = High-risk
Key Predictors	Symptoms, comorbidities, cancer type, age	Performance status, comorbidities, monocyte count, mucositis
Primary Use	Identify low-risk patients for outpatient care	Identify low-risk patients who are stable at presentation

Classification by Infection Source

Another way to classify neutropenic fever initially is by whether an infection is documented or its source is identified. The International Immunocompromised Host Society outlines three types:

Microbiologically Documented Infection: A pathogen is isolated from cultures with a clinical infection site.
Clinically Documented Infection: A clinical infection focus exists, but no pathogen is isolated.
Unexplained Fever: No infection focus or pathogen is found after investigation. This is presumed bacterial and requires immediate empiric antibiotics.

Conclusion

Understanding what is a neutropenic fever classification involves recognizing that it's a multi-faceted process using systems like MASCC and CISNE for risk stratification and categorization based on infection documentation. These classifications are crucial for timely and appropriate management of this life-threatening condition. Accurate classification helps tailor treatment, allowing low-risk patients to potentially receive outpatient care while high-risk patients get intensive inpatient care, optimizing outcomes and reducing risks.

Frequently Asked Questions

The primary purpose is to stratify patients into different risk groups (high vs. low) to determine the appropriate level of care, such as deciding between outpatient and inpatient management, and to guide the selection of antibiotic therapy.

High-risk patients have a greater probability of experiencing severe complications and may require inpatient care, prolonged or profound neutropenia, and have significant comorbidities. Low-risk patients have a lower chance of complications, shorter anticipated neutropenia, and fewer or no comorbidities, potentially allowing for outpatient treatment.

The MASCC score is calculated by assigning points to various patient characteristics, such as symptoms, presence of comorbidities like COPD, cancer type, outpatient status, and age. A score of 21 or greater indicates low risk, while a score less than 21 suggests high risk.

The CISNE score is particularly useful for assessing risk in patients with solid tumors who are initially stable and being evaluated in the emergency department. Some studies suggest it may be more specific than MASCC for identifying truly low-risk patients in this setting.

Unexplained fever refers to cases where a patient has neutropenic fever but no specific clinical focus of infection or an identified pathogen is found, even after performing cultures. It is presumed to be a bacterial infection requiring immediate empiric antibiotic treatment.

High-risk factors include anticipated prolonged and profound neutropenia (ANC < 100 cells/µL for > 7 days), significant comorbidities (e.g., hypotension, pneumonia), uncontrolled or progressive cancer, and organ insufficiency.

No. Classification tools like the MASCC score help identify low-risk patients who can be safely treated with oral antibiotics in an outpatient setting, with close follow-up. However, high-risk patients require mandatory hospitalization.

The ANC is a defining component of neutropenic fever. The severity and expected duration of neutropenia, as indicated by the ANC, are critical factors in risk classification, with lower and more prolonged counts correlating with higher risk.