MASCC Risk Index for Febrile Neutropenia

Why use it

Febrile neutropenia (fever + ANC <500 cells/µL or ANC 500–1000 cells/µL expected to fall below 500) is a common and potentially life-threatening complication of myelosuppressive chemotherapy, affecting approximately 10–50% of patients with solid tumors and 80% of those with hematologic malignancies. Traditionally, all patients were hospitalized for IV antibiotics, but the MASCC score enables safe identification of the low-risk subset (~60% of febrile neutropenia episodes) who can be managed outpatient with oral antibiotics (ciprofloxacin + amoxicillin-clavulanate), reducing unnecessary hospitalizations, healthcare costs, and hospital-acquired infections.

About

The MASCC (Multinational Association for Supportive Care in Cancer) Risk Index was developed by Klastersky and colleagues from a prospective multinational study of 756 cancer patients with febrile neutropenia. Published in the Journal of Clinical Oncology in 2000, the MASCC score identifies patients with febrile neutropenia who are at low risk for serious complications (septic shock, bacteremia, ICU admission, death) and may therefore be candidates for outpatient management with oral antibiotics instead of inpatient IV antibiotics. The score incorporates seven clinical characteristics weighted by their association with favorable outcomes. A total score ≥21 identifies the low-risk group (serious complication rate ~6%, mortality rate <1%), while a score <21 identifies high-risk patients requiring inpatient IV antibiotic therapy. The MASCC score is endorsed by ESMO (European Society for Medical Oncology), IDSA (Infectious Diseases Society of America), and NCCN guidelines for febrile neutropenia management.

When to use

• Any adult cancer patient presenting with febrile neutropenia (temperature ≥38.3°C or ≥38.0°C sustained ×1h, with ANC <500 cells/µL or anticipated to fall below 500)
• Triage decision: inpatient IV antibiotics vs. outpatient oral antibiotics
• Following 24–48h of IV antibiotics in hospitalized patients who have clinically improved — consider step-down to oral therapy if score improves
• Not validated for: pediatric patients, stem cell transplant recipients within 30 days, patients with prolonged neutropenia (>7 days anticipated), documented bacteremia

Formula

Pearls & pitfalls

• The MASCC score has good discriminatory power (AUC 0.86) for identifying low-risk patients — but even low-risk patients require careful selection for outpatient therapy and reliable follow-up.
• The "burden of illness" item (Item 1) is the single highest-weighted item (+5 for no or mild symptoms) — a clinically unwell patient almost certainly warrants inpatient management regardless of total score.
• Hematologic malignancy (vs. solid tumor) is an independent risk factor in the MASCC model — it reduces the score by including the hematologic malignancy modifier.
• Solid tumors and lymphomas with no history of prior fungal infection score higher (better prognosis) than acute leukemia or multiple myeloma patients.
• The MASCC score should NOT be used in: stem cell transplant recipients during engraftment, patients with prolonged neutropenia (>7 days), ANC <100 cells/µL, documented bacteremia, or organ failure.
• Even a MASCC score ≥21 does not eliminate risk — approximately 6% of low-risk patients still develop serious complications. Reliable patient selection, education, and follow-up are essential.
• Some centers use the CISNE (Clinical Index of Stable Febrile Neutropenia) score as a complementary tool for solid tumor patients with apparently stable febrile neutropenia.
• Growth factor support (G-CSF) does not change the MASCC classification — it may shorten duration of neutropenia but is not part of the scoring.

Next steps

MASCC ≥21 (Low Risk): Consider outpatient oral antibiotic therapy — ciprofloxacin 500 mg BID + amoxicillin-clavulanate 500/125 mg TID (or 875/125 mg BID) for 7–10 days. Prerequisites: reliable patient/caregiver, 24h access to medical care, no allergy, no GI issues preventing oral absorption, hemodynamically stable. Daily follow-up by phone or clinic. Hospitalize immediately if deterioration. MASCC <21 (High Risk): Inpatient IV antibiotics required — antipseudomonal beta-lactam (piperacillin-tazobactam 4.5 g IV q6h, cefepime 2 g IV q8h, or meropenem 1 g IV q8h). Add vancomycin if MRSA risk factors (catheter-related, skin/soft tissue infection, hemodynamic instability). Antifungal therapy if fever persists ≥96h.

Evidence

Klastersky J et al. The Multinational Association for Supportive Care in Cancer Risk Index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol. 2000;18(16):3038-3051. PMID:10944139. Derivation cohort: 756 patients (16 centers, 8 countries). Score ≥21: serious complication rate 6%, mortality 1%. Score <21: serious complication rate 36%, mortality 13%. AUC 0.86. IDSA 2010, ESMO 2016, and NCCN guidelines recommend MASCC for risk stratification in febrile neutropenia.

References

1. Klastersky J et al. The Multinational Association for Supportive Care in Cancer Risk Index. J Clin Oncol. 2000;18(16):3038-3051. — link
2. Freifeld AG et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2011;52(4):e56-93. — link
3. Carmona-Bayonas A et al. Prediction of serious complications in patients with seemingly stable febrile neutropenia (CISNE). J Clin Oncol. 2015;33(20):2233-2241. — link