Patients with chemotherapy-induced neutropenic fever who are at high risk for serious complications

Patients with any of the following characteristics are considered to be at high risk for serious complications during episodes of neutropenic fever:

Receipt of cytotoxic therapy sufficiently myelosuppressive to result in anticipated severe neutropenia (ANC <500 cells/mcL) for >7 days*

MASCC risk index score <21^Δ

CISNE score of ≥3^Δ (in patients with solid tumors)

Presence of any active uncontrolled comorbid medical problems, including, but not limited to:

Signs of severe sepsis or septic shock (eg, hemodynamic instability, mental status changes of new onset, respiratory dysfunction, oliguria)
Oral or gastrointestinal mucositis that interferes with swallowing or causes severe diarrhea
Gastrointestinal symptoms, including abdominal pain, nausea and vomiting, or diarrhea
Intravascular catheter infection, especially catheter tunnel infection
New pulmonary infiltrate or hypoxemia
Underlying chronic lung disease
Complex infection at the time of presentation

Alemtuzumab or CAR-T cell use within the past two months

Uncontrolled or progressive cancer^¶

Evidence of hepatic insufficiency (defined as aminotransferase levels >5 times normal values) or renal insufficiency (defined as a creatinine clearance of <30 mL/minute)

ANC: absolute neutrophil count; MASCC: Multinational Association for Supportive Care in Cancer; CISNE: Clinical Index of Stable Febrile Neutropenia; CAR: chimeric antigen receptor.
* The authors use an anticipated ANC threshold of <500 cells/microL for >7 days to consider a patient at high risk for serious complications. It should be noted that the Infectious Diseases Society of America and the National Comprehensive Cancer Network guidelines use an ANC threshold of ≤100 cells/microL for >7 days^[1,2]. At the time that the patient presents with neutropenic fever, it is not always possible to anticipate whether the patient will have severe neutropenia (<500 cells/microL) for >7 days. Clinical circumstances that are likely to result in severe neutropenia for >7 days put patients at high risk for serious complications; these criteria are most likely to be met following induction chemotherapy for acute leukemia and during the pre-engraftment phase of myeloablative hematopoietic cell transplantation (particularly allogeneic).
¶ Defined as any leukemic patient not in complete remission or a nonleukemic patient with evidence of disease progression after more than two courses of chemotherapy.
Δ Refer to the associated UpToDate topic review for details about the MASCC risk index and the CISNE score.

Data adapted from:

Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2011; 52:e56.
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related infections. Version 1.2018. Available at: http://www.nccn.org (Accessed on August 01, 2018).
Taplitz RA, Kennedy EB, Bow EJ, et al. Outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America clinical practice guideline update. J Clin Oncol 2018; 36:1443.

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Patients with chemotherapy-induced neutropenic fever who are at high risk for serious complications