Guidelines for the Management of

Febrile Neutropenia
MICHAEL GABAY, PHARMD, JD, BCPS
Director, Drug Information Group and Prior Authorization Services
Clinical Assistant Professor
MARIA TANZI, PHARMD
Clinical Assistant Professor, Drug Information Group
University of Illinois at Chicago
College of Pharmacy
Chicago, Illinois
F
or patients receiving chemotherapy,
febrile neutropenia often is associated
with immediate hospitalization and
institution of empiric broad-spectrum
antibiotic therapy.
1
Although the condition
remains a major source of morbidity and
mortality, advances in treatment have
significantly improved outcomes.
2

Historically, mortality was extremely highrates
approached 90% in a 1962 study involving patients with
gram-negative bacteremia and severe underlying dis-
ease.
3
More recent data from the Surveillance and Con-
trol of Pathogens of Epidemiologic Importance Project
found mortality rates of 33.4% with coagulase-nega-
tive staphylococci, 22.8% with methicillin-susceptible
Staphylococcus aureus, and 17.7% with methicillin-resis-
tant S. aureus (MRSA) bloodstream infections in 2,340
patients with underlying malignancies.
4
Although the definition of febrile neutropenia varies
within clinical studies, both the Infectious Diseases Soci-
ety of America (IDSA) and the National Comprehensive
Cancer Network (NCCN) define fever as a single oral
temperature of at least 38.3C (101F) without any obvi-
ous environmental cause.
5,6
In addition, a febrile state is
defined as a temperature of at least 38C (100.4C) for
at least 1 hour. An absolute neutrophil count (ANC) fewer
than 1,000 cells/mcL often is used to define neutropenia.
1

The lower the neutrophil count, the greater the risk for
infection.
5
Beyond the quantity of neutrophils, the dura-
tion of neutropenia also can impact infection risk. A pro-
tracted neutropenic state can significantly increase the
potential for infection.
Causes of Neutropenia
And Infectious Complications
The neutropenia observed in patients with malig-
nancy usually is the direct result of cancer chemother-
apy.
7
Neutropenia can be so severe that subsequent
cycles may be delayed or require dose reductions,
thereby potentially impacting the efficacy of the che-
motherapy regimen in the future.
8
Certain single-agent
and combination regimens carry a high (>20%) risk for
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febrile neutropenia. Table 1 contains examples of such
chemotherapy regimens.
9
In patients with malignancy who develop febrile neu-
tropenia, a variety of pathogens may be responsible
for infectious complications. Bacteria are the primary
causes of initial infection early in the course of febrile
neutropenia.
6
The predominant categories of bacterial
pathogens identified as the source of infection have
changed over time.
10
In the late 1950s and early 1960s,
gram-positive organisms, such as S. aureus, commonly
were recognized as causative agents. Since that time,
the primary bacterial cause underlying febrile neutro-
penia has fluctuated back and forth from gram-nega-
tive organisms (ie, Escherichia coli, Klebsiella spp, and
Pseudomonas spp) in the late 1960s and early 1970s
to gram-positive organisms in the 1990s, to an emer-
gence of gram-negative organisms again in the new
millennium. Today, coagulase-negative staphylococci,
S. aureus, viridans group streptococci, and enterococci
are the most common gram-positive pathogens
6
and
E. coli, Klebsiella spp, Enterobacter spp, and P. aerug-
inosa are the most common gram-negative species.
Fungal infections such as Candida and Aspergillus can
occur later in the course of prolonged neutropenia.
Patient Risk Assessment
Assessments of the risk for neutropenia and infec-
tious complications are important components in the
care of patients with malignancy. These assessments
not only evaluate which patients may be at risk for
febrile neutropenia but also attempt to predict the
probability of serious complications and whether a
low-risk individual may safely receive outpatient treat-
ment with oral antibiotics.
6
A variety of risk models have been studied to identify
patient-, disease-, and treatment-related factors associ-
ated with the risk for developing neutropenia and its asso-
ciated complications.
11
In addition to risk models, studies
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Table 1. Chemotherapy Regimens at High Risk for Febrile Neutropenia
a
Cancer Type Regimen
Bladder MVAC (methotrexate, vinblastine, doxorubicin, cisplatin)
Breast Docetaxel plus trastuzumab
AT (doxorubicin plus paclitaxel or docetaxel)
TAC (docetaxel, doxorubicin, cyclophosphamide)
Esophageal and gastric Docetaxel-cisplatin-fluorouracil
Melanoma Dacarbazine-based combinations
Myelodysplastic syndrome Decitabine
Non-Hodgkins lymphoma ICE (ifosfamide, carboplatin, etoposide)
CHOP-14 (cyclophosphamide, doxorubicin, vincristine, prednisone)
DHAP (dexamethasone, cisplatin, cytarabine)
BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine,
procarbazine, prednisone)
Ovarian Topotecan
Paclitaxel or docetaxel
Pancreatic Gemcitabine-docetaxel
Sarcoma MAID (mesna, doxorubicin, ifosfamide, dacarbazine)
Small cell lung Topotecan
Testicular VeIP (vinblastine, ifosfamide, cisplatin)
VIP (etoposide, ifosfamide, cisplatin)
BEP (bleomycin, etoposide, cisplatin)
TIP (paclitaxel, ifosfamide, cisplatin)
a
Does not contain all high-risk regimens.
Based on reference 9.
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of individual risk factors also have been conducted to
aid in identifying patients at greatest risk.
12
Although
there is no consensus nomogram for risk assessment, the
NCCN has developed a risk categorization for patients
based on disease, chemotherapy regimen, patient risk
factors, and treatment intent (ie, curative vs palliative).
9

This scheme categorizes patients as having either a high
(>20%), intermediate (10%-20%), or low (<10%) risk
for developing febrile neutropenia. Table 2 lists patient
risk factors for experiencing a poor clinical outcome or
infection-associated complications, as noted in the 2010
NCCN Myeloid Growth Factor guidelines.
9
The identification of patients at low risk who may
be treated on an outpatient basis with oral antibiotic
therapy is an important consideration in the manage-
ment of febrile neutropenia. The Multinational Associa-
tion for Supportive Care in Cancer (MASCC) risk scoring
index (Table 3)
13
accurately identifies those at low risk
for complications associated with febrile neutropenia
who may then be treated with a more convenient and
cost-effective option. The MASCC index was validated
in a prospective, multinational study where a MASCC
score of at least 21 identified low-risk patients with a
positive predictive value of 91%, specificity of 68%, and
sensitivity of 71%.
13
In addition, the IDSA and the NCCN
have identified various individual factors that favor a
low risk for severe infection among patients with neu-
tropenia (Table 4).
5,6
Clinical Presentation
Febrile neutropenia should be suspected in any
patient who has received chemotherapy in the prior 4
to 6 weeks and presents with a fever or a general feel-
ing of malaise.
14
An infection may be present in these
patients even without fever because a lack of neutro-
phils may negatively impact the ability to mount a suffi-
cient immune response. A thorough history and physical
examination should be completed to identify the site of
infection; however, a definitive infection site may never
be discovered.
14,15
This examination should include the
skin, mucous membranes, fundi, sinuses, and the peri-
anal area.
15
All peripheral and central catheter sites
should be inspected for signs of infection.
The date and the medications involved in the most
recent chemotherapy treatment should be obtained.
In addition, any history of prior prophylactic antibiot-
ics should be noted because this therapy could alter the
patients microflora and influence subsequent antibiotic
choice.
14
Initial laboratory evaluations include a complete
blood count with differential, liver function tests, lipase,
a complete chemistry panel, and a full set of cultures (ie,
sputum, blood, and urine).
15
Cultures should be drawn
from every peripheral and central access point. Chest
radiographs should be obtained even in patients with-
out obvious pulmonary symptoms. If local signs or symp-
toms exist, consider acquiring additional imaging studies
or laboratory tests that may provide more information
regarding symptom etiology. Although patients may
present with only fever and malaise, signs and symptoms
of sepsis, such as hypotension and cardiopulmonary com-
promise, also may occur during initial presentation.
14,15
Management and Treatment
USE OF ANTIMICROBIALS
As discussed previously, patients with neutropenia are
at risk for developing serious infections that can have a
substantial impact on morbidity and mortality. Therefore,
therapies aimed at eliminating the most likely infectious
pathogens are the primary treatments used for manag-
ing patients with febrile neutropenia. In 2002, the IDSA
Table 2. Risk Factors for Poor
Clinical Outcomes or Infection-
Associated Complications
Sepsis syndrome
Age 65 y or older
Severe neutropenia, defined as an absolute
neutrophil count <100 cells/mcL
Neutropenia lasting >10 d
Pneumonia
Invasive fungal infection
Other clinically documented infections
Hospitalization at the time of fever
Prior episode of febrile neutropenia
Based on reference 9.
Table 3. MASCC Risk Scoring Index
a
Extent of illness (choose 1)
No symptoms (5 points)
Mild symptoms (5 points)
Moderate symptoms (3 points)
No hypotension (5 points)
No chronic obstructive pulmonary disease
(4 points)
Solid tumor or no fungal infection (4 points)
No dehydration (3 points)
Outpatient at onset of fever (3 points)
Age <60 y (2 points)
a
A score of 21 or higher indicates the patient is likely to be at
low risk for complications.
MASCC, Multinational Association for Supportive Care in Cancer
Based on reference 13.
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published guidelines on the use of antimicrobial agents
in neutropenic patients with cancer.
5
An update to these
guidelines is expected in 2010. More recently, the NCCN
published guidelines on the prevention and treatment of
cancer-related infections.
6
Both sets of guidelines recom-
mend that empiric antimicrobial therapy be initiated in
all neutropenic patients at the onset of fever. The selec-
tion of empiric therapy should be based on a variety of
factors such as a patients infectious risk, potential sites
of infection, and local antimicrobial sensitivity and resis-
tant patterns (Table 5).
6
For patients at low risk for complications (Tables 4 and
5), oral antimicrobial therapy can be given.
5,6
Both sets
of guidelines recommend an oral regimen that contains
ciprofloxacin plus amoxicillin-clavulanate. The NCCN
recommends ciprofloxacin plus clindamycin for patients
with a penicillin allergy.
6
If fluoroquinolone prophylaxis
was used, the NCCN guidelines recommend against oral
therapy. Outpatient management may be appropriate
for low-risk patients who meet certain criteria, such as
consenting to home care, having a telephone, having
access to emergency facilities, having an adequate and
supportive home environment, and being within 1-hour
travel time to a medical facility or physicians office.
Patients at high risk for severe infections should be
treated in the hospital with IV antimicrobials, accord-
ing to the IDSA and NCCN guidelines.
5,6
Both guidelines
recommend various monotherapy and combination regi-
mens, with vancomycin recommended for select patients
(Table 6). Some of the monotherapy and combination
regimens differ between the 2 sets of guidelines. For
monotherapy, the NCCN guidelines state that ceftaz-
idime has weak gram-positive coverage and is associ-
ated with increased breakthrough infections, suggesting
that the utility of this agent is limited.
6
With respect to
vancomycin as empiric therapy, the IDSA recommends
that this agent be used for patients with clinically sus-
pected serious catheter-related infections, known col-
onization with penicillin- and cephalosporin-resistant
pneumococci or MRSA, positive results of a blood cul-
ture for gram-positive bacteria before final identification
and susceptibility testing, or hypotension or other evi-
dence of cardiovascular impairment.
5
The NCCN guide-
lines recommend that vancomycin be used for patients
meeting any of the same criteria as the IDSA guidelines,
in addition to patients with a soft tissue infection or those
with risk factors for viridans group streptococcal bactere-
mia.
6
The NCCN guidelines strongly recommend against
the use of empiric vancomycin for patients not meeting
these criteria because of concerns about resistance and
breakthrough infections. These guidelines also comment
on the use of agents such as linezolid (Zyvox, Pharma-
cia), daptomycin (Cubicin, Cubist), and quinupristin-dal-
fopristin (Synercid, Monarch) and state that use of these
Table 4. Factors Favoring Low Risk for Severe
Infection in Patients With Neutropenia
a
IDSA 2002 Guidelines NCCN 2009 Guidelines
Absolute neutrophil count of 100 cells/mcL
Absolute monocyte count of 100 cells/mcL
Normal findings on a chest radiograph
Nearly normal renal and hepatic function tests
Duration of neutropenia is <7 d
Resolution of neutropenia expected in <10 d
No IV catheter-site infection
Early evidence of bone marrow recovery
Malignancy in remission
Peak temperature of <39C
No neurologic or mental changes
No appearance of illness
No abdominal pain
No comorbid conditions such as shock, hypoxia,
pneumonia, or other deep-organ infection, vomiting,
or diarrhea
No high-risk factors
a
AND most of the following:
Outpatient status at the time of development of
fever
No associated acute comorbid illnesses
Anticipated short duration of severe neutropenia,
defined as <7 d
Good performance status
No renal or hepatic insufficiency
OR
A score of 21 on the MASCC Risk Index (see Table 3)
IDSA, Infectious Diseases Society of America; MASCC, Multinational Association for Supportive Care in Cancer;
NCCN, National Comprehensive Cancer Network
a
High-risk factors are listed on page FEV-3 of v.2.2009 of the NCCN Practice Guidelines for the Prevention
and Treatment of Cancer-Related Infections.
Based on references 5 and 6.
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antimicrobials should be limited to specific situations
involving infections caused by documented vancomy-
cin-resistant organisms or for patients in whom vanco-
mycin is not an option.
Patients with febrile neutropenia who are clinically
unstable, such as those with sepsis, should be initiated on
combination therapy that includes a broad-spectrum
-lactam (eg, imipenem-cilastatin, meropenem, or piper-
acillin-tazobactam [Zosyn, Wyeth]) plus an aminoglyco-
side and vancomycin.
6
The addition of antifungal
therapy (eg, fluconazole or an echinocandin) also
should be considered for patients not receiving antifun-
gal prophylaxis.
Alterations in the initial empiric regimen are needed
for patients who are not responding to therapy.
5,6
The
NCCN guidelines recommend assessing the appropriate-
ness of antimicrobials for isolated pathogens in patients
with documented infection who are not responding to
empiric therapy.
6
In addition, for patients with fever of
unknown origin who are unstable, antimicrobials should
be broadened to include coverage of anaerobes, resis-
tant gram-negative rods and gram-positive organisms,
and Candida. Empiric antifungal therapy is generally ini-
tiated after 4 to 7 days in patients who remain febrile.
The NCCN guidelines state that the duration of antimi-
crobial therapy is determined by several factors such as
the underlying site of infection, causative organisms, and
the patients clinical condition, response to treatment,
and time to neutrophil recovery.
6
For patients with fever
of unknown origin, antimicrobial therapy is generally
continued until the ANC is at least 500 cells/mcL, assum-
ing the patient is afebrile for at least 24 hours before dis-
continuation. For patients with documented infections,
the NCCN guidelines acknowledge that most clinicians
treat patients until the ANC recovers to 500 cells/mcL
or more, but they recommend using a defined course of
therapy appropriate for the specific infection. The dura-
tions for antimicrobial therapies suggested in the NCCN
guidelines are summarized in Table 7.
6
The duration of antimicrobial therapy is treated differ-
ently in the IDSA guidelines.
5
The IDSA guidelines state
that if no infection is identified after 3 days of treatment,
the ANC is at least 500 cells/mcL for 2 consecutive days,
and the patient has been afebrile for at least 48 hours,
antimicrobials can be stopped. The guidelines also rec-
ommend that for patients with prolonged neutrope-
nia, therapy can be stopped in low-risk patients who
are clinically well and afebrile for 5 to 7 days. Antimi-
crobial therapy can be stopped after 2 weeks in patients
with persistent fever on day 3 and prolonged neutrope-
nia, as long as no documented infection is found and the
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Table 5. Factors Influencing
Initial Antimicrobial Selection
Infection risk assessment (ie, low vs high risk)
Antimicrobial susceptibilities of pathogens
isolated locally
The most commonly potentially infecting
organisms, including antimicrobial-resistant
pathogens, such as ESBL-producing
gram-negative rods or VRE
Colonization or previous infection with MRSA
Potential site of the infection
Importance of broad spectrum antimicrobial
coverage that includes antipseudomonal coverage
Previous antimicrobial use
Clinical instability such as organ dysfunction,
hypotension
Drug allergy
ESBL, extended spectrum -lactamase;
MRSA, methicillin-resistant Staphylococcus aureus;
VRE, vancomycin-resistant enterococcus
Based on reference 6.
Table 6. Empiric Antimicrobial
Therapy for Febrile Neutropenia
IDSA 2002 Guidelines NCCN 2009 Guidelines
Monotherapy
Imipenem/cilastatin
Meropenem
Cefepime
Ceftazidime
Monotherapy
Imipenem/cilastatin
Meropenem
Piperacillin/tazobactam
Cefepime
Ceftazidime
(limited utility)
Combination therapy
Aminoglycoside plus
antipseudomonal
penicillin
Aminoglycoside plus
cefepime, ceftazidime,
or carbapenem
Combination therapy
Aminoglycoside plus
antipseudomonal
penicil lin with or
without -lactamase
inhibitor
Aminoglycoside plus
cefepime or ceftazidime
Ciprofloxacin plus
antipseudomonal
penicillin
Vancomycin
(for select patients)
Vancomycin plus
cefepime, ceftazi-
dime, or carbapen-
em with or without
aminoglycoside
Vancomycin
(for select patients)
Monotherapy or
combination therapy
IDSA, Infectious Diseases Society of America;
NCCN, National Comprehensive Cancer Network
Based on references 5 and 6.
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patient is clinically stable.
PROPHYLACTIC ANTIMICROBIALS
Both the IDSA and NCCN guidelines comment on
the use of antimicrobial prophylaxis for afebrile neu-
tropenic patients.
5,6
The IDSA guidelines recommend
against the routine use of antimicrobial prophylaxis
because of emerging resistance.
5
Antimicrobial prophy-
laxis with trimethoprim-sulfamethoxazole (TMP-SMX)
only is recommended to prevent Pneumocystis jiroveci
pneumonitis in patients at risk for this infection. Anti-
fungal prophylaxis with fluconazole and antiviral pro-
phylaxis with acyclovir or ganciclovir are recommended
for patients undergoing allogenic hematopoietic stem
cell transplantation. The NCCN guidelines include a
detailed discussion on antimicrobial prophylaxis, which
is beyond the scope of this review; however, key recom-
mendations include fluoroquinolone prophylaxis, with
levofloxacin (Levaquin, Ortho-McNeil-Janssen) as the
preferred agent for patients expected to have neutro-
penia for more than 7 days, and TMP-SMX for patients
at risk for Pneumocystis jiroveci infections.
PROPHYLACTIC USE OF COLONY-STIMULATING FACTORS
Reducing the incidence, severity, and duration of
neutropenia is another important treatment strategy
used for managing patients with febrile neutropenia.
Colony-stimulating factors (CSFs) are used to prevent
neutropenia in patients who are receiving myelosup-
pressive chemotherapy.
16
These agents regulate the
proliferation, differentiation, maturation, and functional
activation of neutrophils. The CSFs are classified into
2 groups: granulocyte-CSFs (filgrastim [Neupogen,
Amgen] and pegfilgrastim [Neulasta, Amgen]) and a
granulocyte-macrophage CSF (sargramostim [Leukine,
Genzyme]).
17-19
The labeled indications for filgrastim,
pegfilgrastim, and sargramostim vary; a summary of
these indications is presented in Table 8.
17-19
Filgrastim should be initiated 24 to 72 hours after com-
pletion of chemotherapy at a daily dose of 5 mcg/kg.
17

Therapy should be continued through the post-nadir
recovery to normal or near-normal levels. Filgrastim
should not be given the same day chemotherapy is
administered. Pegfilgrastim should also be initiated 24 to
72 hours after the completion of chemotherapy and not
administered on the same day chemotherapy is given.
18

Table 7. Suggested Durations
Of Antimicrobial Therapy for Patients
With Documented Infections
Infection Duration of Therapy
Skin and soft tissue 7-14 d
Blood stream infections
Gram-negative
Gram-positive
10-14 d
7-14 d
Sinusitis 10-21 d
Bacterial pneumonia 10-21 d
Fungal (mold and yeast)
Candida
Mold (eg, Aspergillus)
Minimum of 2 wk
after first negative
blood culture
Minimum of 12 wk
Viral
Herpes simplex/Varicella
zoster
Influenza
7-10 d
5-10 d
Based on reference 6.
Table 8. Labeled Indications for CSFs
CSFs FDA-Approved Indications
Filgrastim
(Neupogen, Amgen)
Cancer patients receiving myelosuppressive chemotherapy
Patients with AML receiving induction or consolidation chemotherapy
Cancer patients receiving BMT
Patients undergoing peripheral blood progenitor cell collection and therapy
Patients with severe chronic neutropenia
Pegfilgrastim
(Neulasta, Amgen)
Cancer patients receiving myelosuppressive chemotherapy
Sargramostim
(Leukine, Genzyme)
Patients with AML receiving induction or consolidation chemotherapy
Patients undergoing peripheral blood progenitor cell collection and therapy
Cancer patients receiving BMT
Use in BMT failure or engraftment delay
AML, acute myeloid leukemia; BMT, bone marrow transplant; CSFs, colony-stimulating factors
Based on references 17-19.
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Pegfilgrastim is given as one dose of 6 mg per treatment
cycle. Sargramostim is given at a dose of 250 mcg/m
2

per day, also initiated 24 to 72 hours after the completion
of chemotherapy, and continued through the post-nadir
recovery period.
19
The American Society of Clinical
Oncology (ASCO) guidelines recommend that use of
sargramostim is limited to its labeled indications.
16
RECOMMENDATIONS FOR USE OF CSFS
In 2006, ASCO published an update to its 2000
recommendation on the use of CSFs.
16
Data have
shown that prophylactic use of CSFs reduces the inci-
dence, length, and severity of chemotherapy-related
neutropenia, and decreases rates of infection.
20,21
Use
of CSFs is recommended as primary prophylaxis of
febrile neutropenia for patients at high risk based
on age, medical history, disease characteristics, and
risk for myelotoxicity associated with a chemother-
apy regimen. Available data support the use of CSFs
with chemotherapy regimens that have a 20% or
greater risk for febrile neutropenia (Table 1). In addi-
tion, CSFs may be beneficial for patients undergoing
nonmyelosuppressive therapy but who have risk fac-
tors for febrile neutropenia or infectious complications.
A summary of ASCOs recommendations is presented
in Table 9.
16
The CSFs are not recommended for rou-
tine treatment of afebrile neutropenia and use should
be avoided in patients receiving a combination of che-
motherapy and radiation.
The 2010 recommendations from NCCN on the use
of CSFs are summarized in Table 10.
9
These guidelines,
which are similar to the ASCO guidelines, also recom-
mend the prophylactic use of CSFs with chemother-
apy regimens that have at least a 20% risk for febrile
neutropenia. In addition, patients are considered to be
at high risk if they experienced a previous neutropenic
complication in the immediate previous cycle with no
plan to reduce the dose intensity of the chemotherapy
regimen. When deciding if CSFs should be used, clini-
cians are encouraged to consider the intent of the che-
motherapy regimen. For example, is therapy curative
or is it being used for symptom control? For patients in
the intermediate-risk category (10%-20%), NCCN rec-
ommends that if the risk is based on patient-specific
Table 9. ASCO Recommendations on Use of CSFs
As primary prophylaxis of febrile neutropenia for patients at high risk based on age, medical history, disease
characteristics, and risk for myelotoxicity associated with a chemotherapy regimen.
For patients undergoing nonmyelosuppressive therapy but who have risk factors for febrile neutropenia or
infectious complications due to bone marrow compromise or other comorbidities.
As secondary prophylaxis in patients who have previously experienced an episode of febrile neutropenia
(without primary prophylaxis) when a reduction in dose of chemotherapy is not appropriate.
Use can be considered as adjunctive treatment of febrile neutropenia for patients at high-risk for infectious
complications.
To allow for a modest to moderate increase in dose-density and dose-intensity of chemotherapy regimens.
As an adjunct to progenitor-cell transplantation.
For reduction of neutropenia in patients with AML with initial or repeat induction chemotherapy or completion
of consolidation therapy.
To increase ANC in patients with myelodysplastic syndrome.
Following completion of initial induction therapy or first post-remission course of chemotherapy for ALL.
For limited use with refractory or relapsed AML (data suggest only a few shortened days of neutropenia can
be expected).
As prophylaxis in patients 65 y and older with diffuse aggressive lymphoma undergoing CHOP or more
aggressive regimens.
For patients being treated with lethal doses of total body radiotherapy.
For pediatric patients, CSFs can be used for primary prophylaxis and as secondary prophylaxis or as
adjunctive therapy for high-risk patients; the risk for secondary myeloid leukemia or myelodysplastic
syndrome should be considered in children with ALL.
ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia; ANC, absolute neutrophil count; ASCO, American Society of Clinical
Oncology; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; CSFs, colony-stimulating factors
Based on reference 16.
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factors, then use of CSFs is reasonable. However, if the
intermediate risk is based on the chemotherapy regi-
men, then use of less myelosuppressive therapies or a
dose reduction should be considered.
Conclusion
Febrile neutropenia remains a significant source of
morbidity and mortality for patients receiving chemo-
therapy. Risk factors and models have been evaluated to
aid in determining which patients may be at high risk for
complications and which patients may be at low risk and
therefore benefit from treatment with more cost-effec-
tive and convenient medication regimens. The IDSA and
NCCN have developed guidelines for the prevention and
treatment of infections associated with febrile neutro-
penia. In addition, the NCCN and ASCO have published
guidelines regarding the appropriate use of myeloid
growth factors for this condition. Appropriate therapy
in selected patients can significantly improve outcomes
and reduce complications of febrile neutropenia.
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Table 10. NCCN Recommendations on CSFs for Febrile Neutropenia
Risk for Febrile Neutropenia
Associated With Chemotherapy
Regimen
Goal of Chemotherapy Regimen
Curative/Adjunctive Prolong Survival/QoL Symptom Management/QoL
High (>20%) CSF CSF CSF
Intermediate (10%-20%) May be considered May be considered May be considered
Low (<10%) No CSF
a
No CSF No CSF
a
Only consider CSF if a patient is at significant risk for serious medical consequences of febrile neutropenia, including death.
CSFs, colony-stimulating factors; NCCN, National Comprehensive Cancer Network; QoL, quality of life
Based on reference 9.
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