Neutropenia natural history, complications and prognosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:
Overview
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Natural History
Febrile Neutropenia
Diagnosis
In patients with severe neutropenia, the neutrophil-mediated inflammatory process in the setting of infection is often blunted. Fever can be the sole presenting symptom. The risk of infection increases with the degree and duration of neutropenia with prolonged neutropenia defined as >7 days.
Per 2002 IDSA [1] and 2013 ASCO [2] guidelines, febrile neutropenia requires both of the following criteria:
1) Fever: single oral temperature >38.3 C/101 F or sustained temperature >38 C/100.4 F for 1 hour.
2) Severe neutropenia: ANC< 500 cells/microliter.
Pathogenesis
1) Damage to the immune system and/or mucosal barriers by an underlying malignancy.
2) Damage to the immune system and/or mucosal barriers by chemotherapy.
The majority of cases of neutropenic fever are attributed to chemotherapy-induced mucositis, which permits endogenous bacterial and fungi to seed the bloodstream. Defects in neutrophilic phagocytosis, as well as antibody production, immune complex clearance, and T-cell mediated cytotoxic killing by hematologic malignancies or immunosuppressive chemotherapies predispose to infection by encapsulated and intracellular organisms.
Common pathogens include
Gram-positive bacteria
- Staphylococci (including MRSA; S.epidermidis accounts for 50% of all Gram-positive febrile neutropenia)
- Streptococci
- Enterococci (including VRE)
- Listeria
Gram-negative bacteria
- Enterobacteriaceae (E.coli, Klebsiella, Enterobacter, including ESBL-producers)
- Pseudomonas
- Citrobacter
- Acinetobacter
- Neisseria
- Haemophilus
- Salmonella
Fungi (rare in low-risk patients)
- Candida
- Aspergillus
- Cryptococcus
- Reactivation of endemic fungi (Histoplasma, Blastomyces, Coccidioides)
Anaerobes are less commonly identified, yet can cause intra-abdominal, pelvic, or periodontal infections.
Diagnostic Evaluation
- Targeted history
- Detailed physical exam focusing on: mental status, skin, eyes, mucus membranes and oropharynx, lungs, abdomen, and perineum (digital rectal exam should be avoided in neutropenic patients)
- CBC with differential
- Serum electrolytes, creatinine, liver function tests
- Urinalysis with culture
- Blood cultures including separate cultures from each indwelling catheter
- Cultures from any suspected sites of infection including serum or BAL galactomannan if at increased risk for aspergillosis
- Consider chest radiographs or CT scan of the chest and/or abdomen to detect infiltrates and bowel wall thickening in the appropriate clinical context
Despite prompt and thorough evaluation, a source of infection is identified in less than 1/3 of patients. Bacteremia, present in up to 25%, often serves as the only source of positive culture data [1]. As such, rapid risk stratification and appropriate empiric treatment is necessary.
Prognosis
Low risk: typically patients with solid tumors on chemotherapy plus the following:
- Anticipated neutropenia (ANC<500 cells/microliter) <7 days
- No significant hepatic or renal dysfunction
- No significant comorbidities**
- MASCC Risk Score >21 (PPV 91%, specificity 68%, sensitivity 71%)
High risk
- Anticipated neutropenia (ANC<500 cells/microliter) >7 days
- Significant hepatic or renal dysfunction
- Significant comorbidities**
- Disease progression
- MASCC Risk Score <21 (PPV 91%, specificity 68%, sensitivity 71%)
**Significant comorbidities:
- Hemodynamic instability
- Mucositis
- GI symptoms
- Acute neurological changes
- Intravascular catheters
- Pulmonary infiltrates or underlying chronic lung disease
References
- ↑ 1.0 1.1 Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. (2011). "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. 52 (4): e56–95. PMID 21258094.
- ↑ Flowers CR, Seidenfeld J, Bow EJ, Karten C, Gleason C, Hawley DK, Kuderer NM, Langston AA, Marr KA, Rolston KV, Ramsey SD (2013). "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". 31 (6): 794–810. PMID 23319691.