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Granulocyte Colony Stimulating Factor – Adult/Pediatric – Inpatient/Ambulatory

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Granulocyte Colony Stimulating Factor -
Adult/Pediatric - Inpatient/Ambulatory
Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
Table of Contents
EXECUTIVE SUMMARY ........................................................................................................... 3
SCOPE ...................................................................................................................................... 7
METHODOLOGY ...................................................................................................................... 8
DEFINITIONS ............................................................................................................................ 9
INTRODUCTION ....................................................................................................................... 9
RECOMMENDATIONS .............................................................................................................10
UW HEALTH IMPLEMENTATION ............................................................................................15
APPENDIX A ............................................................................................................................16
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2
CPG Contact for Content:
Sara Shull, PharmD, MBA, BCPS Drug Policy Analyst
Phone Number: (608) 262-1817
Email Address: ssmith-shull@uwhealth.org
CPG Contact for Changes:
Mary Mably, RPh, BCOP - Pharmacy
Phone Number: (608) 263-1263
Email Address: mmably@uwhealth.org
Guideline Author(s):
Jennie Piccolo, PharmD, BCOP
Coordinating Team Members:
Sara Shull, PharmD, MBA, BCPS
Review Individuals/Bodies:
Arjang Djamali, MD
David Hager, PharmD, BCPS, CNSC
Mark Juckett, MD
Mary Mably, RPh, BCOP
Marie Pietruszka, PharmD, BCPS, AAHIVP, CNSC
Michael Reed, RPh, BCOP, BCPS
Jill Strayer, PharmD, BCPS
Andrew Urban, MD
Committee Approvals/Dates:
Chemotherapy Review Council- September, 2015
UW Health Pharmacy and Therapeutics Committee- September 2015
Release Date: September 2015 | Next Review Date: September 2018
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3
Executive Summary
Guideline Overview
These clinical practice guidelines are intended to guide clinicians in the use of
granulocyte colony stimulating factor (GCSF) in adult and pediatric patients. Graded
recommendations for indications, dosing, administration, and precautions for use are
included.
Key Practice Recommendations
1. Prevention of febrile neutropenia in cancer patients receiving myelosuppressive
chemotherapy
1.1. GCSF should be used as primary prevention in patients receiving
chemotherapy with a 20% or greater risk of neutropenic fever (Class I, Level
of Evidence A)
1.1.1. Secondary prevention can be considered in patients with previous dose
modifications, delays in therapy, or neutropenic fever
1.2. GCSF should be given at least 24 hours after the last dose of chemotherapy
(Class I, Level of Evidence A)
1.3. Dosing: (Class I, Level of Evidence A)
1.3.1. All adult patients who weigh 80 kg or less should receive GCSF 300
mcg subcutaneously once daily (Class I, Level of Evidence A)
1.3.2. All adult patients who weigh greater than 80 kg should receive GCSF
480 mcg subcutaneously once daily (Class I, Level of Evidence A)
1.3.3. Pediatric patients will receive GCSF 5 mcg/kg/day intravenously or
subcutaneously (Class I, Level of Evidence A)
1.4. Duration of Therapy:
1.4.1. Adult and pediatric patients will continue with daily GCSF administration
until the ANC is 500 cells/mm3 on two consecutive days (Class I, Level
of Evidence A)
1.4.2. Pediatric patients who remain on Children’s Oncology Group (COG)
protocols and are ON study may continue GCSF as is specified by the
ANC target of the COG protocol. Pediatric patients who are NOT ON
study should follow ANC targets as specified above.
2. Treatment of febrile neutropenia in patients with greater risk of mortality
2.1. No improvement in overall survival has been shown for the use of GCSF in
the treatment of neutropenic fever. GCSF should only be considered for the
treatment of febrile neutropenia in patients with risk factors for greater
mortality. (Class IIa, Level of Evidence A)
2.2. Risk Factors: age > 65 years, sepsis syndrome, ANC < 100, anticipated
prolonged neutropenia (greater than 10 days) (Class IIa, Level of Evidence
A)
2.3. Dosing:
2.3.1. All adult patients who weigh 80 kg or less should receive GCSF 300
mcg subcutaneously once daily (Class I, Level of Evidence A)
2.3.2. All adult patients who weigh greater than 80 kg should receive GCSF
480 mcg subcutaneously once daily (Class I, Level of Evidence A)
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4
2.3.3. Pediatric patients will receive GCSF 5 mcg/kg/day intravenously or
subcutaneously (Class I, Level of Evidence A)
2.4. Duration of Therapy:
2.4.1. Patients will continue with daily GCSF administration until the ANC is
500 cells/mm3 on two consecutive days (Class I, Level of Evidence A)
3. Mobilization in patients undergoing stem cell collection
3.1. Patients will receive twice daily GCSF to assist in promoting stem cell
production and release from the bone marrow prior to stem cell collection for
autologous peripheral stem cell transplants (Class I, Level of Evidence A)
3.2. Dosing:
3.2.1. All adult patients who weigh less than 60 kg should receive GCSF 300
mcg subcutaneously twice daily (Class I, Level of Evidence A)
3.2.2. All adult patients who weigh between 60 and 78 kg should receive
GCSF 300 mcg subcutaneously in the morning and 480 mcg
subcutaneously in the evening (Class I, Level of Evidence A)
3.2.3. All adult patients who weigh greater than 78 kg should receive GCSF
480 mcg subcutaneously twice daily (Class I, Level of Evidence A)
3.2.4. Pediatric patients will receive GCSF 10 mcg/kg daily subcutaneously
(Class I, Level of Evidence A)
3.3. Duration of therapy:
3.3.1. Patients will continue on GCSF until an adequate amount of stem cells
for autologous transplant have been collected. (Class I, Level of
Evidence A)
4. In patients undergoing autologous peripheral blood or bone marrow transplant
exception: multiple myeloma patients
4.1. Patients undergoing autologous peripheral blood or bone marrow transplant
can receive GCSF to assist with engraftment and shorten the length of
hospital stay. (Class I, Level of Evidence A)
4.2. Multiple myeloma patients will not receive GCSF as part of their autologous
peripheral blood or bone marrow transplant. (Class I, Level of Evidence A)
4.3. Dosing:
4.3.1. All adult patients who weigh 80 kg or less should receive GCSF 300
mcg subcutaneously once daily (Class I, Level of Evidence A)
4.3.2. All adult patients who weigh greater than 80 kg should receive GCSF
480 mcg subcutaneously once daily (Class I, Level of Evidence A)
4.3.3. Pediatric patients will receive GCSF 5 mcg/kg/day intravenously or
subcutaneously (Class I, Level of Evidence A)
4.4. Duration of Therapy:
4.4.1. Adult and pediatric patients will continue with daily GCSF administration
until the ANC is 500 cells/mm3 on two consecutive days (Class I, Level
of Evidence A)
4.4.2. Pediatric patients who remain on Children’s Oncology Group (COG)
protocols and are ON study may continue GCSF as is specified by the
ANC target of the COG protocol. Pediatric patients who are NOT ON
study should follow ANC targets as specified above.
5. In patients undergoing allogeneic cord-blood transplants
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5
5.1. Patients undergoing allogeneic cord-blood transplants can receive GCSF to
assist with engraftment and shorten the length of neutropenia. (Class IIb,
Level of Evidence C)
5.2. Patients receiving other allogeneic peripheral blood stem cell transplants
should not receive GCSF as it increases the risk of severe graft versus host
disease. (Class I, Level of Evidence A)
5.3. Dosing:
5.3.1. All adult patients who weigh 80 kg or less should receive GCSF 300
mcg subcutaneously once daily (Class I, Level of Evidence A)
5.3.2. All adult patients who weigh greater than 80 kg should receive GCSF
480 mcg subcutaneously once daily (Class I, Level of Evidence A)
5.3.3. Pediatric patients will receive GCSF 10 mcg/kg/day intravenously
(Class I, Level of Evidence A)
5.4. Duration of Therapy:
5.4.1. Adult and pediatric patients will continue with daily GCSF administration
until the ANC is 500 cells/mm3 on two consecutive days (Class I, Level
of Evidence A)
5.4.2. Pediatric patients who remain on Children’s Oncology Group (COG)
protocols and are ON study may continue GCSF as is specified by the
ANC target of the COG protocol. Pediatric patients who are NOT ON
study should follow ANC targets as specified above.
6. Drug-induced neutropenia (Class IIb, Level of Evidence C)
6.1. GCSF should not be used as the primary treatment of drug-induced
neutropenia, other than in the populations specified in this guideline. Dose
reduction, discontinuation, or temporary cessation of the offending
medication(s) should be the primary treatment for these patients. (Class IIb,
Level of Evidence C)
6.2. GCSF can only be considered in certain situations where patients who
remain neutropenic despite dose reduction, discontinuation, or temporary
cessation of the offending medication(s). (Class IIb, Level of Evidence C)
7. Drug-induced leukopenia in solid organ transplant patients on chronic
immunosuppression or antiviral agents (i.e. ganciclovir, valganciclovir,
mycophenolate, azathioprine)
7.1. GCSF should only be considered in conjunction with dose reduction,
discontinuation, or temporary cessation of the offending medication(s).
(Class IIb, Level of Evidence B)
7.2. Dosing:
7.2.1. All adult patients who weigh 80 kg or less should receive GCSF 300
mcg subcutaneously once daily (Class I, Level of Evidence A)
7.2.2. All adult patients who weigh greater than 80 kg should receive GCSF
480 mcg subcutaneously once daily (Class I, Level of Evidence A)
7.2.3. Pediatric patients will receive GCSF 5 mcg/kg/day intravenously or
subcutaneously (Class I, Level of Evidence A)
7.3. Duration of Therapy:
7.3.1. Adult and pediatric patients may initiate therapy at ANC values of less
than 1000 cells/mm3. Patients may continue daily administration until
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6
the ANC is greater than 1000 cells/mm3 for one day. (Class IIb, Level of
Evidence C)
8. Drug-induced leukopenia in HIV patients on anti-retroviral therapy (i.e.
zidovudine) or immune suppressive antiviral agents (i.e. ganciclovir,
valganciclovir)
8.1. In patients who are on anti-retroviral therapy for the treatment of HIV or anti-
viral medications with bone marrow suppressive side effects, GCSF could
be considered in conjunction with dose reduction, discontinuation, or
temporary cessation of the offending medication(s). (Class IIb, Level of
Evidence B)
8.2. Neutropenia associated with the AIDS disease process is considered an
inappropriate use by the University Health-system Consortium Colony
Stimulating Factors expert panel. (Class IIb, Level of Evidence B)
8.3. Dosing:
8.3.1. All adult patients who weigh 80 kg or less should receive GCSF 300
mcg subcutaneously once daily (Class I, Level of Evidence A)
8.3.2. All adult patients who weigh greater than 80 kg should receive GCSF
480 mcg subcutaneously once daily (Class I, Level of Evidence A)
8.3.3. Pediatric patients will receive GCSF 5 mcg/kg once daily intravenously
or subcutaneously (Class I, Level of Evidence A)
8.4. Duration of Therapy
8.4.1. Adult and pediatric patients will initiate therapy at ANC values of less
than 1000 cells/mm3. Patients will continue daily administration until
the ANC is greater than 1000 cells/mm3 for one day. (Class IIb, Level of
Evidence C)
9. Severe Chronic Neutropenia
9.1. Patients with symptomatic congenital neutropenia, cyclic neutropenia, or
idiopathic neutropenia will receive chronic GCSF to reduce the incidence
and duration of sequelae of neutropenia (i.e. fever, infection, oropharyngreal
ulcers)(3,4) (Class I, Level of Evidence B)
9.2. Dosing:
9.2.1. Patients receiving GCSF for severe chronic neutropenia will receive a
daily dose titrated to an ANC goal of 1500 cells/mm3(3,4) (Class I, Level
of Evidence B)
9.2.2. It is appropriate to use the patient’s home dose of GCSF in these
situations (Class I, Level of Evidence B)
9.3. Duration of therapy
9.3.1. Patients will continue daily GCSF indefinitely. The dose will be titrated
to maintain an ANC target of 1500 cells/mm3 (3,4) (Class I, Level of
Evidence B)
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Scope
Disease/Condition(s):
All adult and pediatric patients with neutropenia including the following:
1. Prevention and treatment of febrile neutropenia in patients receiving
myelosuppressive therapy
2. Patients undergoing mobilization for stem cell collection
3. Patients undergoing autologous peripheral blood or bone marrow transplant
4. Patients undergoing allogeneic cord blood transplant
5. Patients with drug-induced leukopenia secondary to chronic immunosuppression
or antiviral agents following solid organ transplant
6. Patients with drug-induced leukopenia secondary to anti-retroviral therapy for
the treatment of HIV
7. Patients with severe chronic neutropenia
Clinical Specialty:
Bone Marrow Transplant, Hematology, Oncology, Solid Organ Transplant, Infectious
Diseases
Intended Users:
This guideline is intended to be used by physicians, advanced practice providers,
pharmacists, and nurses.
Objective(s):
These clinical practice guidelines are intended to guide clinicians in the use of GCSF in
adult and pediatric patients including recommendations for indications, dosing,
administration, and precautions for use.
Target Population:
Patients with neutropenia
Interventions and Practices Considered:
1. Indications of appropriate GCSF use
2. ANC goals for all indications
3. Adult and pediatric dosing recommendations for all indications
4. Monitoring parameters
Major Outcomes Considered:
Successful management of patients with neutropenia
Cost savings from appropriate utilization of treatment strategies.
Guideline Metrics:
Successful management of patients with neutropenia.
Cost savings from appropriate utilization of treatment strategies
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8
Methodology
Methods Used to Collect/Select the Evidence:
Review of the following:
1. National guideline recommendations including National Comprehensive Cancer
Network (NCCN), American Society of Clinical Oncology (ASCO), Infectious
Diseases Society of America (IDSA), and European Organization for the
Research and Treatment of Cancer (EORTC)
2. FDA package inserts using Drugs@FDA website
3. Existing UW Health Clinical Practice Guidelines
4. PubMed database with the keywords: granulocyte colony stimulating factor,
GCSF, filgrastim, neutropenia
Methods Used to Assess the Quality and Strength of the Evidence:
A modified Grading of Recommendations Assessment, Development and Evaluation
(GRADE) developed by the American Heart Association and American College of
Cardiology has been used to assess the Quality and Strength of the Evidence in this
Clinical Practice Guideline.(1)
Rating Scheme for the Strength of the Evidence:
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9
Methods Used to Formulate the Recommendations:
Review of standard drug databases, pertinent guidelines and literature with treatment
effect size and estimate of certainty of the treatment effect established according to the
rating scheme.
Definitions
1. Absolute neutrophil count (ANC) – the total number of neutrophils in the
peripheral blood
2. Allogeneic stem cell transplant – peripheral blood or bone marrow transplant
where the recipient receives a donor’s cells
3. Autologous stem cell transplant – peripheral blood or bone marrow transplant
where the recipient receives his/her own cells
4. Cord-blood transplant – peripheral blood transplant where the recipient receives
progenitor cells harvested from an umbilical cord
5. Febrile neutropenia – a single oral or tympanic temperature of ≥38.3°C (101°F),
or a temperature of ≥ 38.0°C (100.4°F) sustained over an hour AND an ANC of ≤
500 cells/mm3. (2)
6. Granulocyte colony stimulating hormone (GCSF) – a hormone in the body that
regulates the production of neutrophils within the bone marrow and affects
neutrophil progenitor cell proliferation, differentiation, and end-cell functional
activation.(3)
7. Mobilization – the use of GCSF with or without chemotherapy to stimulate the
production of progenitor cells in the bone marrow and their release into the
peripheral blood
8. Neutropenia – hematologic abnormality where the ANC is <1000 cells/mm3.
Severe neutropenia is defined as ANC < 500 cells/mm3
9. Stem cell collection – the collection of peripheral blood progenitor cells by
leukapheresis procedure
Introduction
Granulocyte colony stimulating factor (GCSF) is an analogue of the human GCSF
produced by Escherichia coli (E. coli) bacteria through recombinant DNA technology.
GCSF is FDA approved for the reduction of the duration and severity of febrile
neutropenia in adult and pediatric cancer patients receiving chemotherapy, in patients
undergoing stem cell collection, and in patients with severe chronic neutropenia. (3, 4)
GCSF is an expensive medication with few available alternatives. The American
Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN)
and European Organization for Research and Treatment of Cancer (EORTC) clinical
practice guidelines define appropriate indications for oncology patients to receive GCSF
as well as the appropriate ANC goal.(5-7) Recent literature supports expanded
indications for GCSF such as the treatment of drug- induced leukopenia in solid organ
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10
transplant patients and patients infected with human immunodeficiency virus (HIV);
however, ANC goals and durations of therapy have not yet been established at this
time.(8-13) This guideline was developed based on the available evidence in the
literature to establish defined standards for GCSF use at the UWHC.
Recommendations
The following recommendations are separated into appropriate indications with
dosing and duration of therapy of each. Monitoring parameters will apply to all
indications.
1. Prevention of febrile neutropenia in cancer patients receiving myelosuppressive
chemotherapy
a. GCSF should be used as primary prevention in patients receiving
chemotherapy with a 20% or greater risk of neutropenic fever (5-7) (Class
I, Level of Evidence A)
i. Secondary prevention can be considered in patients with previous
dose modifications, delays in therapy, or previous incidence of
neutropenic fever (5-7) (Class I, Level of Evidence A)
b. GCSF should be given at least 24 hours after the last dose of
chemotherapy (5-7) (Class I, Level of Evidence A)
c. Dosing:
i. All adult patients who weigh 80 kg or less should receive GCSF
300 mcg subcutaneously once daily (5-7) (Class I, Level of
Evidence A)
ii. All adult patients who weigh greater than 80 kg should receive
GCSF 480 mcg subcutaneously once daily (5-7) (Class I, Level of
Evidence A)
iii. Pediatric patients will receive GCSF 5 mcg/kg/day intravenously or
subcutaneously (5-7) (Class I, Level of Evidence A)
d. Duration of Therapy:
i. Adult and pediatric patients will continue with daily GCSF
administration until the ANC is 500 cells/mm3 on two consecutive
days (5-7) (Class I, Level of Evidence A)
ii. Pediatric patients who remain on Children’s Oncology Group
(COG) protocols and are ON study may continue GCSF as is
specified by the ANC target of the COG protocol. Pediatric patients
who are NOT ON study should follow ANC targets as specified
above.
2. Treatment of febrile neutropenia in patients with greater risk of mortality
a. No improvement in overall survival has been shown for the use of GCSF
in the treatment of neutropenic fever. GCSF should only be considered
for the treatment of febrile neutropenia in patients with risk factors for
greater mortality. (5,6) (Class IIa, Level of Evidence A)
b. Risk Factors: age > 65 years, sepsis syndrome, ANC < 100, anticipated
prolonged neutropenia (greater than 10 days) (5,6) (Class IIa, Level of
Evidence A)
c. Dosing:
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11
i. All adult patients who weigh 80 kg or less should receive GCSF
300 mcg subcutaneously once daily (5-7) (Class I, Level of
Evidence A)
ii. All adult patients who weigh greater than 80 kg should receive
GCSF 480 mcg subcutaneously once daily (5-7) (Class I, Level of
Evidence A)
iii. Pediatric patients will receive GCSF 5 mcg/kg/day intravenously or
subcutaneously (5-7) (Class I, Level of Evidence A)
d. Duration of Therapy
i. Patients will continue with daily GCSF administration until the ANC
is 500 cells/mm3 on two consecutive days (5-7) (Class I, Level of
Evidence A)
3. Mobilization in patients undergoing stem cell collection
a. Patients will receive twice daily GCSF to assist in promoting stem cell
production and release from the bone marrow prior to stem cell collection
for autologous peripheral stem cell transplants (5-7) (Class I, Level of
Evidence A)
b. Dosing:
i. All adult patients who weigh less than 60 kg should receive GCSF
300 mcg subcutaneously twice daily (5-7) (Class I, Level of
Evidence A)
ii. All adult patients who weigh between 60 and 78 kg should receive
GCSF 300 mcg subcutaneously in the morning and 480 mcg
subcutaneously in the evening (5-7) (Class I, Level of Evidence A)
iii. All adult patients who weigh greater than 78 kg should receive
GCSF 480 mcg subcutaneously twice daily (5-7) (Class I, Level of
Evidence A)
iv. Pediatric patients will receive GCSF 10 mcg/kg daily
subcutaneously (5-7) (Class I, Level of Evidence A)
c. Duration of therapy:
i. Patients will continue on GCSF until an adequate amount of stem
cells for autologous transplant have been collected. (5-7) (Class I,
Level of Evidence A)
4. In patients undergoing autologous peripheral blood or bone marrow transplant
exception: multiple myeloma patients
a. Patients undergoing autologous peripheral blood or bone marrow
transplant can receive GCSF to assist with engraftment and shorten the
length of hospital stay. (5-7) (Class I, Level of Evidence A)
b. Multiple myeloma patients will not receive GCSF as part of their
autologous peripheral blood or bone marrow transplant. (5-7) (Class I,
Level of Evidence A)
c. Dosing:
i. All adult patients who weigh 80 kg or less should receive GCSF
300 mcg subcutaneously once daily (5-7) (Class I, Level of
Evidence A)
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12
ii. All adult patients who weigh greater than 80 kg should receive
GCSF 480 mcg subcutaneously once daily (5-7) (Class I, Level of
Evidence A)
iii. Pediatric patients will receive GCSF 5 mcg/kg/day intravenously or
subcutaneously (5-7) (Class I, Level of Evidence A)
d. Duration of Therapy:
i. Adult and pediatric patients will continue with daily GCSF
administration until the ANC is 500 cells/mm3 on two consecutive
days (5-7) (Class I, Level of Evidence A)
ii. Pediatric patients who remain on Children’s Oncology Group
(COG) protocols and are ON study may continue GCSF as is
specified by the ANC target of the COG protocol. Pediatric patients
who are NOT ON study should follow ANC targets as specified
above.
5. In patients undergoing allogeneic cord-blood transplants
a. Patients undergoing allogeneic cord-blood transplants can receive GCSF
to assist with engraftment and shorten the length of neutropenia. (5-7)
(Class IIb, Level of Evidence C)
b. Patients receiving other allogeneic peripheral blood stem cell transplants
should not receive GCSF as it increases the risk of severe graft versus
host disease.(5) (Class I, Level of Evidence A)
c. Dosing:
i. All adult patients who weigh 80 kg or less should receive GCSF
300 mcg subcutaneously once daily (5-7) (Class I, Level of
Evidence A)
ii. All adult patients who weigh greater than 80 kg should receive
GCSF 480 mcg subcutaneously once daily (5-7) (Class I, Level of
Evidence A)
iii. Pediatric patients will receive GCSF 10 mcg/kg/day intravenously
(5-7) (Class I, Level of Evidence A)
d. Duration of Therapy:
i. Adult and pediatric patients will continue with daily GCSF
administration until the ANC is 500 cells/mm3 on two consecutive
days (5-7) (Class I, Level of Evidence A)
ii. Pediatric patients who remain on Children’s Oncology Group
(COG) protocols and are ON study may continue GCSF as is
specified by the ANC target of the COG protocol. Pediatric patients
who are NOT ON study should follow ANC targets as specified
above.
6. Drug-induced neutropenia
a. GCSF should not be used as the primary treatment of drug-induced
neutropenia, other than in the populations specified in this guideline.
Dose reduction, discontinuation, or temporary cessation of the offending
medication(s) should be the primary treatment for these patients. (14)
(Class IIb, Level of Evidence C)
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13
b. GCSF can only be considered in certain situations where patients who
remain neutropenic despite dose reduction, discontinuation, or temporary
cessation of the offending medication(s). (14) (Class IIb, Level of
Evidence C)
7. Drug-induced leukopenia in solid organ transplant patients on chronic
immunosuppression or antiviral agents (i.e. ganciclovir, valganciclovir,
mycophenolate, azathioprine)
a. GCSF should only be considered in conjunction with dose reduction,
discontinuation, or temporary cessation of the offending medication(s).(8-
11) (Class IIb, Level of Evidence B)
b. Dosing:
i. All adult patients who weigh 80 kg or less should receive GCSF
300 mcg subcutaneously once daily (5-7) (Class I, Level of
Evidence A)
ii. All adult patients who weigh greater than 80 kg should receive
GCSF 480 mcg subcutaneously once daily (5-7) (Class I, Level of
Evidence A)
iii. Pediatric patients will receive GCSF 5 mcg/kg/day intravenously or
subcutaneously (5-7) (Class I, Level of Evidence A)
c. Duration of Therapy:
i. Adult and pediatric patients may initiate therapy at ANC values of
less than 1000 cells/mm3. Patients may continue daily
administration until the ANC is greater than 1000 cells/mm3 for one
day.(8-11) (Class IIb, Level of Evidence C)
8. Drug-induced leukopenia in HIV patients on anti-retroviral therapy (i.e.
zidovudine) or immune suppressive antiviral agents (i.e. ganciclovir,
valganciclovir)
a. In patients who are on anti-retroviral therapy for the treatment of HIV or
anti-viral medications with bone marrow suppressive side effects, GCSF
could be considered in conjunction with dose reduction, discontinuation, or
temporary cessation of the offending medication(s). (12,13) (Class IIb,
Level of Evidence B)
b. Neutropenia associated with the AIDS disease process is considered an
inappropriate use by the University Health-system Consortium Colony
Stimulating Factors expert panel. (12,13) (Class IIb, Level of Evidence B)
c. Dosing:
i. All adult patients who weigh 80 kg or less should receive GCSF
300 mcg subcutaneously once daily (5-7) (Class I, Level of
Evidence A)
ii. All adult patients who weigh greater than 80 kg should receive
GCSF 480 mcg subcutaneously once daily (5-7) (Class I, Level of
Evidence A)
iii. Pediatric patients will receive GCSF 5 mcg/kg once daily
intravenously or subcutaneously (5-7) (Class I, Level of Evidence
A)
d. Duration of Therapy
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14
i. Adult and pediatric patients will initiate therapy at ANC values of
less than 1000 cells/mm3. Patients will continue daily
administration until the ANC is greater than 1000 cells/mm3 for one
day.(12,13) (Class IIb, Level of Evidence C)
9. Severe Chronic Neutropenia
a. Patients with symptomatic congenital neutropenia, cyclic neutropenia, or
idiopathic neutropenia will receive chronic GCSF to reduce the incidence
and duration of sequelae of neutropenia (i.e. fever, infection,
oropharyngreal ulcers) (4,15,16) (Class I, Level of Evidence B)
b. Dosing:
i. Patients receiving GCSF for severe chronic neutropenia will receive
a daily dose titrated to an ANC goal of 1500 cells/mm3(3,4) (Class I,
Level of Evidence B)
ii. It is appropriate to use the patient’s home dose of GCSF in these
situations
c. Duration of therapy
i. Patients will continue daily GCSF indefinitely. The dose will be
titrated to maintain an ANC target of 1500 cells/mm3(3,4) (Class I,
Level of Evidence B)
10. Monitoring parameters
a. Complete blood count (CBC) with differential daily (3, 4) (Class I, Level of
Evidence A)
i. Note: if the white blood cell count is < 0.5 cells/mm3, a neutrophil
level will not be reported
b. Bone Pain(3, 4) (Class I, Level of Evidence A)
i. Patients experiencing bone pain with GCSF administration can be
treated with non-steroidal anti-inflammatory drugs (NSAIDS).
c. Toxicity
i. Hypersensitivity reactions(3, 4) (Class I, Level of Evidence A)
1. Generally characterized by systemic symptoms involving at
least two body systems (example reactions: rash, urticaria,
facial edema, wheezing, dyspnea, hypotension, and
tachycardia).
2. Reactions tend to occur within the first 30 minutes after
administration
3. Reactions can be managed in most cases with the
administration of antihistamines, steroids, bronchodilators,
and/or epinephrine. Symptoms are likely to recur in patients
that are rechallenged.
ii. Splenic rupture(3, 4) (Class I, Level of Evidence A)
1. Monitor left upper abdominal pain and/or shoulder tip pain.
iii. Acute Respiratory Distress Syndrome (ARDS) (3, 4) (Class I, Level
of Evidence A)
1. Monitor patient temperature, respiratory status, breath
sounds and chest X-ray as needed.
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 10/2015CCKM@uwhealth.org

15
UW Health Implementation
Potential Benefits:
This guideline has been developed based on best evidence based recommendations.
By implementing the parameters set forth in the guideline, patients will receive filgrastim
appropriately and safely allowing for controlled cost of this medication.
Potential Harms:
Some patients with neutropenia may be excluded based on guideline criteria despite
possible benefit from GCSF.
Implementation Plan/Tools
1. Dosing guidelines will be built into Health Link to be visible upon order entry of
GCSF
2. Education will be provided to health care providers
3. Guideline is attached to GCSF medication record
4. Guideline is available on UConnect
5. Education will be provided as necessary
Disclaimer
CPGs are described to assist clinicians by providing a framework for the evaluation and
treatment of patients. This Clinical Practice Guideline outlines the preferred approach
for most patients. It is not intended to replace a clinician’s judgment or to establish a
protocol for all patients. It is understood that some patients will not fit the clinical
condition contemplated by a guideline and that a guideline will rarely establish the only
appropriate approach to a problem.
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 10/2015CCKM@uwhealth.org

16
Appendix A
Table 1: Summary of Recommendations
Indication Dose Duration of Therapy
Febrile neutropenia
prevention in cancer
patients receiving
myelosuppressive
chemotherapy
ξ Adults ≤ 80 kg should receive GCSF 300 mcg SC
daily
ξ Adults > 80 kg should receive GCSF 480 mcg SC
daily
ξ Pediatric patients should receive GCSF 5
mcg/kg/day IV
Until the ANC is 500 cells/mm3 on two consecutive
days
Exception: Pediatric patients who remain on
Children’s Oncology Group (COG) protocols and
are ON study may continue GCSF as is specified by
the ANC target of the COG protocol.
Febrile neutropenia
treatment
ξ Adults ≤ 80 kg should receive GCSF 300 mcg SC
daily
ξ Adults > 80 kg should receive GCSF 480 mcg SC
daily
ξ Pediatric patients should receive GCSF 5
mcg/kg/day IV
Until ANC is 500 cells/mm3 on two consecutive
days
Mobilization ξ Adults patients < 60 kg should receive GCSF 300
mcg SC BID
ξ Adults 60-78 kg should receive GCSF 300 mcg SC
in the morning and 480 mcg SC in the evening
ξ Adults > 78 kg should receive GCSF 480 mcg SC
BID
ξ Pediatric patients should receive GCSF 10
mcg/kg/day IV
Until an adequate amount of stem cells for
autologous transplant have been collected
Autologous peripheral
blood or bone marrow
transplant
Exception: multiple
myeloma patients
ξ Adults ≤ 80 kg should receive GCSF 300 mcg SC
daily
ξ Adults > 80 kg should receive GCSF 480 mcg SC
daily
ξ Pediatric patients should receive GCSF 5
mcg/kg/day IV
Until ANC is 500 cells/mm3 on two consecutive
days
Exception: Pediatric patients who remain on
Children’s Oncology Group (COG) protocols and
are ON study may continue GCSF as is specified by
the ANC target of the COG protocol.
Allogeneic cord-blood
transplants
ξ Adults ≤ 80 kg should receive GCSF 300 mcg SC
daily
ξ Adults > 80 kg should receive GCSF 480 mcg SC
daily
ξ Pediatric patients should receive GCSF 5
mcg/kg/day IV
Until ANC is 500 cells/mm3 on two consecutive
days
Exception: Pediatric patients who remain on
Children’s Oncology Group (COG) protocols and
are ON study may continue GCSF as is specified by
the ANC target of the COG protocol.
Solid organ transplant
patients: drug-associated
neutropenia
ξ Adults ≤ 80 kg should receive GCSF 300 mcg SC
daily
ξ Adults > 80 kg should receive GCSF 480 mcg SC
daily
ξ Pediatric patients should receive GCSF 5
mcg/kg/day IV
Until ANC is 1000 cells/mm3 for one day
HIV patients: drug-
associated neutropenia
ξ Adults ≤ 80 kg should receive GCSF 300 mcg SC
daily
ξ Adults > 80 kg should receive GCSF 480 mcg SC
daily
ξ Pediatric patients should receive GCSF 5
mcg/kg/day IV
Until ANC is 1000 cells/mm3 for one day
Severe Chronic
Neutropenia
ξ Dose titrated to an ANC goal of 1500 cells/mm3 Indefinitely
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 10/2015CCKM@uwhealth.org

17
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Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 10/2015CCKM@uwhealth.org