Febrile Neutropenia: Identifying High-Risk Patients
Abstract & Commentary
By David J. Pierson, MD, Editor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, is Editor for Critical Care Alert
Synopsis: Understanding of etiologies, management, and outcomes of febrile neutropenia has improved in recent years, and it is now possible to identify patients at high risk for morbidity and mortality using demographic, historical, and laboratory indicators.
Source: Viscoli C, et al. Clin Infect Dis. 2005;40(Suppl 4):s240-s245.
This review from a group of investigators with extensive experience in the management of fever in neutropenic patients provides a concise update on recent trends in the etiologies and outcomes of this condition, and discusses methods for risk stratification based on the most recent multicenter studies. The outlook for patients with febrile neutropenia has improved substantially during the past 25 years. In a large-scale study by the European Organization for Research and Treatment of Cancer (EORTC), published in 1978,1 about 15% of patients with sepsis due to Gram-positive organisms, and more than 20% of those with Gram-negative sepsis, died. Because of improvements in empirical antibiotic therapy and other factors, these mortality rates had fallen to about half of each of those figures, in studies by the EORTC and other groups, by the late 1990s.2 During this period, perhaps abetted by the fact that today’s more aggressive cancer chemotherapy regimens cause more mucosal disruption in the GI tract and hence increased access to the bloodstream by Gram-positive organisms, the latter have replaced Gram-negatives as the predominant bacterial causes of febrile neutropenia. Staphylococcal infections, especially, have become much more common in recent years. The incidence of polymicrobial bloodstream infections has also increased during this time. Viscoli and colleagues emphasize the etiologic importance of local and regional vitiations in microbial prevalence among patients with febrile neutropenia.
Because fever in a severely neutropenic patient may represent either an easily manageable problem that can be handled without hospitalization or a serious threat to life requiring management in the ICU, considerable attention has been devoted to risk stratification. Most recently this attention has focused on identifying patients who are likely to do well without admission to the hospital. Viscoli et al have previously determined factors that forecast a good response to outpatient therapy among patients with febrile neutropenia (see Table 1).3 These factors have to do with the patient’s age, general medical condition, co-morbidities, status with respect to bone marrow function, and indicators of the severity of the current episode and also, importantly, with social and logistical factors (see Table 2).3
| Table 1 |
| Factors Predicting a Low Risk of Medical Complications in Patients with Febrile Neutropenia |
Adapted from: Viscoli C, et al. Clin Infect Dis. 2005;40(Suppl 4):s240-s245; Castagnola E, et al. J Hematother Stem Cell Res. 2000;9:645-649. |
| Table 2 |
| Patient Social and Logistical Factors Associated with a Low Risk of Medical Complications in Neutropenic Fever |
Adapted from: Viscoli C, et al. Clin Infect Dis. 2005;40(Suppl 4):s240-s245; Castagnola E, et al. J Hematother Stem Cell Res. 2000;9:645-649. |
As reported by Viscoli et al in their review, the Multinational Association for Supportive Care in Cancer attempted to establish a quantitative index for identifying low-risk patients who may be managed without admission to the hospital.4 These investigators derived a numerical score using data from 756 patients. They then prospectively assessed 383 additional patients using the score to validate it. The score assigned either 5 points if the patient was asymptomatic or had only mild symptoms, or 3 points if the symptoms were judged to be moderate in severity. Additional points were assigned according to clinical and other factors, as follows: absence of hypotension, 5 points; absence of COPD, 5 points; having a solid tumor for underlying disease, or not having previously had a fungal infection, 4 points; no dehydration, 3 points; outpatient status, 3 points; and age younger than 60 years, 2 points. The maximum possible score using this scheme is 26 points. Using a cut-off of 20 points or less for being at high risk, 73% of the patients in the initial derivation set were identified as being at low risk, for a positive predictive value of 94%.
Commentary
Febrile neutropenia is a common and always potentially life-threatening problem in the management of cancer. This review nicely summarizes current concepts of etiologies and outcomes in this condition. It also clarifies what is known about risk stratification. Although the studies summarized focused on identifying patients at low risk for mortality and morbidity, other investigators have listed factors that portend an especially poor prognosis. Talcott and colleagues5 classified patients with febrile neutropenia into 4 groups, using information available on the first day of fever. These investigators considered patients in 3 of the 4 groups to be at especially high risk for major complications, and to require hospitalization. These 3 groups were:
- Patients who were already hospitalized for cancer treatments;
- Outpatients with underlying illness either in remission or not progressing who had significant comorbid symptoms, such as pain, nausea, and volume depletion; and,
- Outpatients whose underlying illness was uncontrolled.5
Talcott et al validated the use of this classification system in a subsequent, larger group of patients.6
In evaluating patients with febrile neutropenia, Viscoli et al stress the importance of the underlying burden of illness and the severity of symptoms in determining the potential threat to life represented by fever during a period of neutropenia. Being familiar with the patient, and certain elements of the patient’s living situation, are also key. Use of the factors discussed above may permit more rational decision-making with respect to the need for hospitalization when outpatients manifest neutropenic fever, and also when deciding the optimum level of care and monitoring when hospitalized patients develop this syndrome.
References
- Schimpff SC, et al. J Infect Dis. 1978;137:14-29.
- Viscoli C. Eur J Cancer. 2002;38(Suppl 4):s82-s87.
- Castagnola E, et al. J Hematother Stem Cell Res. 2000;9:645-649.
- Klastersky J, et al. J Clin Oncol. 2000;18:3038-3051.
- Talcott JA, et al. Arch Intern Med. 1988;148:2561-2568.
- Talcott JA, et al. J Clin Oncol. 1994;12:107-114.
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