CISNE Score (Clinical Index of Stable Febrile Neutropenia)

Identifies febrile neutropenia patients at low risk of serious complications.

Refer to the text below the tool for more information on the index and the risk categories.


Clinical Index of Stable Febrile Neutropenia (CISNE) is used to identify stable patients with febrile neutropenia who are at risk of medical complications.

It is addressed to adult outpatients with solid tumor, fever ≥38°C (100.4°F) over 1 hour, and neutropenia (500 cells/mm³or fewer, or 1,000 cells/mm³ with expected decrease to 500).

Complications include hypotension, acute organ failure, arrhythmia, major bleeding, acute abdomen, DIC, delirium.


CISNE Risk of complications Recommendation
0 points, Low risk 1.1% (95% CI 0.3-3.8%) Consider discharge with oral antibiotic.
1 – 2 points, Intermediate risk 6.2% (95% CI 4-9%) Use clinical judgment regarding admission. Consider oncology consultation.
≥3 points, High risk 36% (95% CI 27-38.5%) Admit for IV antibiotics and further investigation, including blood cultures.

Instruction: CISNE can be used only in outpatients aged ≥ 18 years with solid cancer receiving mild/moderate intensity chemotherapy; neutrophil count 500 cells/mm³or fewer, or 1,000 cells/mm³ with expected decrease to 500; fever at least 38°C (100.4°F) over 1 hr and absence of the following: organ failure (renal, cardiac, respiratory); hypotension or septic shock; chronic organ insufficiency; known severe infections.
1ECOG Performance Status ECOG PS 2 = Capable of all self care, but no work activities, out of bed >50% of day
2Stress-induced hyperglycemia Initial blood glucose ≥121 mg/dL (6.7 mmol/L), or ≥250 mg/dL (13.9 mmol/L) in diabetics or if on steroids
3COPD COPD diagnosis on therapy with ≥1 of the following: steroids, supplemental O2, bronchodilators
4Cardiovascular disease history Chronic heart conditions (e.g., cor pulmonale, heart failure, cardiomyopathy, hypertensive heart disease, arrhythmias, valvular disease, other structural malformations), excludes history of single uncomplicated episode of atrial fibrillation
5Mucositis grade ≥2 Painful erythema, edema, or ulcers, but eating/swallowing possible
6Monocyte count
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About CISNE

The Clinical Index of Stable Febrile Neutropenia identifies stable patients with febrile neutropenia who are at risk of medical complications.

CISNE can be used to assess adult outpatients with solid tumor, fever ≥38°C (100.4°F) over 1 hour and neutropenia (defined as: 500 cells/mm³or fewer, or 1,000 cells/mm³ with expected decrease to 500).

It cannot be used in patients who are unwell, exhibiting one of the following:

  • Acute organ failure (renal, cardiac, and respiratory).
  • Decompensation of chronic organ insufficiency.
  • Septic shock and hypotension (systolic BP
  • Known severe infection.
  • Other serious complications that would warrant hospital admission.

Clinically stable patients were defined as without any organ dysfunction, without abnormalities in vital signs and no major infections.

CISNE comprises of 6 predictors of risk, that are assigned a number of points, which is then summed to retrieve the final score:

  0 points 1 point 2 points
ECOG Performance Status <2 - ≥2
Stress-induced hyperglycemia No - Yes
COPD No Yes -
Cardiovascular disease history No Yes -
NCI mucositis grade ≥2 No Yes -
Monocytes ≥200/µL <200/µL -

An external validation study included both solid and hematologic malignancies and showed no significant difference in outcomes for low-risk patients with either type.

 

Result interpretation

CISNE scores range from 0 to 8, where the higher the score, the greater the risk of complications and likelihood of hospitalisation.

CISNE Risk of complications Recommendation
0 points, Low risk 1.1% (95% CI 0.3-3.8%) Consider discharge with oral antibiotic.
1 – 2 points, Intermediate risk 6.2% (95% CI 4-9%) Use clinical judgment regarding admission. Consider oncology consultation.
≥3 points, High risk 36% (95% CI 27-38.5%) Admit for IV antibiotics and further investigation, including blood cultures.

The table below describes the complications referred to by the score:

Complications Described as:
Hypotension Persistent systolic blood pressure
Acute respiratory failure SaO2 <90%, PaO2 2 ≥45 mmHg
Acute renal failure Increase in creatinine >0.3 mg/dL within 48 hours, increase in creatinine to ≥1.5× baseline within prior 7 days, or urine volume
Acute heart failure Rapid onset of dyspnea, pulmonary edema, and oxygen desaturation requiring urgent therapy.
Arrhythmia Altering cardiovascular stability
Major bleeding Critical localization (intracranial, intraspinal, intraocular, retroperitoneal, or pericardial), or associated with reduction in hemoglobin values ≥2 g/dL or bleeding requiring transfusion of two units RBCs
Delirium Acute alteration of mental state with cognitive impairment
Acute abdomen Requiring urgent medical or surgical management
Disseminated intravascular coagulation Widespread hypercoagulable state that can lead to micro- and macrovascular clotting and compromised blood flow
 

Original study and validation

In their 2011 case-control study, Carmona-Bayonas et al. reviewed 861 episodes of febrile neutropenia in outpatients with solid tumors, out of which 692 were considered as clinically stable. The study sought to identify the presenting features that may have predictive value for the prognosis of these patients and the MASCC index was evaluated.

From this cohort, rate of complication was 7.3% and rate of bacteremia 6.2%. The MASCC index demonstrated a low sensitivity to detect complications.

The CISNE prognostic score was subsequently validated in a multicenter study of 1,133 febrile neutropenia stable patients from 25 hospitals.

Complication rates in the validation subset were 1.1% in low-, 6.2% in intermediate-, and 36% in high-risk patients. Areas under the receiver operating characteristic curves in the validation subset were 0.721 (95% CI, 0.669 to 0.768) for Multinational Association for Supportive Care in Cancer (MASCC), and 0.868 (95% CI, 0.827 to 0.903) for CISNE (P = .002 for comparison between CISNE and MASCC).

CISNE has shown it can identify and prevent the premature discharge of FN patients who are apparently clinically stable but who present with underlying risk factors for complications.

 

Comparison to MASCC

The Multinational Association of Supportive Care in Cancer (MASCC) score is another prediction tool that prognoses the outcome and risk of complications in FN patients who undergo chemotherapy.

In a retrospective cohort study of 230 patients presenting with chemotherapy induced febrile neutropenia, the two scores were compared. The MASCC score was less specific (54.2%; 95% Cl 40.8% to 67.1%) in the identification of a low-risk complications cohort.

 

References

Original reference

Carmona-Bayonas A, Gómez J, González-Billalabeitia E, Canteras M, Navarrete A, Gonzálvez ML, Vicente V, Ayala de la Peña F. Prognostic evaluation of febrile neutropenia in apparently stable adult cancer patients. Br J Cancer. 2011; 105(5):612-7.

Validation

Carmona-Bayonas A, Jiménez-Fonseca P, Virizuela Echaburu J, Antonio M, Font C, Biosca M, Ramchandani A, Martínez J, Hernando Cubero J, Espinosa J, Martínez de Castro E, Ghanem I, Beato C, Blasco A, Garrido M, Bonilla Y, Mondéjar R, Arcusa Lanza MÁ, Aragón Manrique I, Manzano A, Sevillano E, Castañón E, Cardona M, Gallardo Martín E, Pérez Armillas Q, Sánchez Lasheras F, Ayala de la Peña F. Prediction of serious complications in patients with seemingly stable febrile neutropenia: validation of the Clinical Index of Stable Febrile Neutropenia in a prospective cohort of patients from the FINITE study. J Clin Oncol. 2015; 33(5):465-71.

Other references

Fonseca PJ, Carmona-Bayonas A, García IM, Marcos R, Castañón E, Antonio M, Font C, Biosca M, Blasco A, Lozano R, Ramchandani A, Beato C, de Castro EM, Espinosa J, Martínez-García J, Ghanem I, Cubero JH, Manrique IA, Navalón FG, Sevillano E, Manzano A, Virizuela J, Garrido M, Mondéjar R, Arcusa MÁ, Bonilla Y, Pérez Q, Gallardo E, Del Carmen Soriano M, Cardona M, Lasheras FS, Cruz JJ, Ayala F. A nomogram for predicting complications in patients with solid tumours and seemingly stable febrile neutropenia. Br J Cancer. 2016; 114(11):1191-8.

Coyne CJ, Le V, Brennan JJ, Castillo EM, Shatsky RA, Ferran K, Brodine S, Vilke GM. Application of the MASCC and CISNE Risk-Stratification Scores to Identify Low-Risk Febrile Neutropenic Patients in the Emergency Department. Ann Emerg Med. 2017; 69(6):755-764.

Flowers CR, Seidenfeld J, Bow EJ, Karten C, Gleason C, Hawley DK, Kuderer NM, Langston AA, Marr KA, Rolston KV, Ramsey SD. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2013; 31(6):794-810.


Specialty: Oncology

Objective: Risk Predictor

Type: Index

No. Of Items: 6

Year Of Study: 2011

Abbreviation: CISNE

Article By: Denise Nedea

Published On: June 4, 2024

Last Checked: June 4, 2024

Next Review: June 4, 2029