DEVITA

NCCN
IDSA
ESMO
ASCO

FEVER AND NEUTROPENIA

Fever is single oral T 38.3C or sustained T 38C
for 1 hour.

Neutropenia is defined as an absolute neutrophil

count (ANC) of <500 cells/mm3 or an ANC that is
expected to decrease to <500 cells/mm3 during the
next 48 hours.

In neutropenic patients, fever should be considered

evidence of infection and treated accordingly.
Bacterial infections may progress quickly in the
absence of granulocytes and appropriate antibiotics
must be started immediately. Empirical
administration of broad-spectrum antibiotics to
neutropenic febrile patients showed early on to
result in improved outcomes and remains the
standard of care.
The initial evaluation consists of a complete history
and physical examination. Important elements of the
history include prior infections or known
colonization with resistant pathogens, as well as
timing of the fever in relation to manipulation of the
central venous catheter if one is present. Special
attention should be given to the mouth, skin,
catheter exit site, and perianal region during the
physical exam.
Initial laboratory studies should include complete
blood count and differential, serum chemistry
including liver function tests, and at least two sets of
blood cultures. Other cultures (urine, sputum,
stool if diarrhea) should not delay the
administration of antibiotics.

An initial chest radiograph in the absence of

symptoms or signs of pulmonary infection is of low
yield in ambulatory adult patients with fever and
neutropenia.

Risk Stratification
One of the key current concepts in the management
of neutropenic fever involves risk stratification: not
all patients who develop fever during chemotherapy-
induced neutropenia have the same risk of a poor
outcome, and this has practical implications for
management (choice of antibiotics, inpatient versus
outpatient setting).
Most adult guidelines endorse the use of the
Multinational Association for Supportive Care in
Cancer (MASCC) index.

Table 1. MASCC Risk Index Factors and Weights

1
Burden of febrile neutropenia refers to general clinical status as
influenced by the febrile neutropenic episode. It is evaluated in
accordance with the following scale: no symptoms (5), mild symptoms (5),
moderate symptoms (3), severe symptoms (0), moribund (0).
2
Chronic obstructive pulmonary disease means active chronic bronchitis,
emphysema, decrease in FEVs, need for oxygen therapy and/or steroids
and/or bronchodilators.
3
Previous fungal infection means demonstrated fungal infection or
empirically treated suspected fungal infection.

4
The points attributed to the variable "burden of febrile neutropenia" are
not cumulative. Thus, the maximum theoretical score is therefore 26. A
score of 21 is considered low risk and a score of < 21 as high risk
(positive predictive value of 91%, specificity of 68%, and sensitivity of
71%)

The pediatric guidelines support the concept of risk

stratification, but emphasize the importance of using
strategies that have been validated locally. The
MASCC index was designed as a tool to identify
adult patients at low risk of complications.

The points are added up, and patients with a score

of 21 points (of 26 possible) are low risk and can
be considered for oral therapy. The index may do so
better in solid tumors than in hematologic
malignancies.

The IDSA guidelines include expert clinical

criteria derived from clinical trials: patients with
neutropenia expected to last 7 days, clinically
unstable or with significant comorbidities,
or high intensity chemotherapy are all high risk
and should be hospitalized for intravenous
antibiotics. Similarly, the
American Society of Clinical Oncology guidelines
present a list of
conditions that makes the outpatients high-risk
independently of
their MASCC score.43
For low-risk patients, it is still important to make
sure they
can tolerate oral agents and have adequate access to
medical care
before deciding to treat them as outpatients with
oral antibiotics.
The antibiotics used for adults have been
ciprofloxacin + amoxicillin/
clavulanic acid80 and moxifloxacin monotherapy.81
Quinolones
should not be used for treatment if patients were
receiving
them for prophylaxis. In penicillin-allergic patients,
the combination
of ciprofloxacin + clindamycin is recommended.43

Initial assessment and investigations

MASCC febrile neutropaenia risk index

Characteristics Score
Burden of illness: no or mild symptoms 5
Burden of illness: moderate symptoms 3
Burden of illness: severe symptoms 0
No hypotension (systolic BP > 90 mmHg) 5
No chronic obstructive pulmonary disease 4
Solid tumour/lymphoma with no previous fungal
infection 4
No dehydration 3
Outpatient status (at onset of fever) 3
Age <60 years 2
Patients with scores 21 are at low risk of
complications. Points attributed
to the variable burden of illness are not cumulative.
The maximum
theoretical score is therefore 26 [2]. Reprinted with
permission. 2000
American Society of Clinical Oncology. All rights
reserved.
BP, blood pressure.

Prognosis:
In the case of FN, prognosis is worst in patients with proven
bacteraemia, with mortality rates of 18% in Gram-negative and
5% in Gram-positive bacteraemia [for bacteraemias due to coagulase-
negative Staphylococcus (CNS) only, no attributable mortality
has been reported] [1]. The presence of a focal site of presumed
infection (e.g. pneumonia, abscess, cellulitis) also makes the
outcome worse. Mortality varies according to the Multinational
Association of Supportive Care in Cancer (MASCC) prognostic
index (Table 1): lower than 5% if the MASCC score is 21, but
possibly as high as 40% if theMASCC score is <15