Transcript e-learning GCSF

e-learning
GCSF
John Murray
Nurse Clinician EBMT
Contents
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What is GCSF
Biology
How was GCSF discovered
History
How was GCSF discovered
GCSF manufacturers
How does it work
Approved uses
Types of GCSF available
Instructions on use
What is GCSF?
• GCSF stands for ‘Granulocyte Colony Stimulating Factor’
• GCSF and Granulocytes are produced by endothelium,
macrophages and other immune cells. There are 3 types of
granulocyte
Neutrophil
Eosinophil
Basophil
• GCSF has 2 structural forms; with 174 & 180 amino acids
• GCSF was first discovered while testing Heamopoetic Stem
Cells (HSCs) for colony stimulating substances.
White Blood Cells
History
1983 Australia
Walter and Eliza
Hall Institute
purified mouse
GCSF
Groups in Japan
Germany & USA
followed in 1986
with human clone
version
Amgen neupogen
(filgrastim) 1989
Chugai –
granocyte
(lenograstim) 1991
1983
1986
1989
1991
How was GCSF discovered?
0
Hence
The
Haemopoietic
When
It was
name
athen
the
single
‘colony-stimulating
substance
possible
stem
cell (1cells
to
discovered
) starts
test
were
substances
proliferating,
factor’
cultured
to stimulate
oron
on
‘CSF’
the
all
a semi
of
comes
granulocytes
colonies
the
solid
cells
from
matrix
and
derived
the
was
0method
discovery
(SSM)
from
called
examine
it‘Granulocyte
(2which
) will remain
colonies
Colony
clustered
were
Stimulating
stimulated
Factor’ or ‘GCSF’
20
20
20
20
10
20
20
20
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10
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Biology
• In order to interact with the cell, there must be GCSF
receptors present
• The GCSF receptor is present on precursor cells in
Bone Marrow
• In response to GCSF, cell signalling mechanisms
instruct the cell to proliferate and differentiate into
mature granulocytes
• Main use is for
• HSC mobilisation
• Decreasing incidence of neutropenia
How does it work?
GCSF binds to surface receptors of neutrophil precursors and
mature neutrophils stimulating
• Proliferation
• Differentiation
• Commitment, and
• End cell function
Approved uses
Most UK centres base their practice on guidelines published by
British Committee for
Standards in Haematology
(BCSH), 2003
American Society of Clinical
Oncology (ASCO), 2006
National Comprehensive
Cancer Network clinical
guidelines
Local policy and procedure must be adhered to, please refer to
Trust SOP agreed criteria
JACIE agreed criteria
Primary prophylaxis
Primary prophylaxis
Not routinely recommended in previously untreated patients undergoing induction chemotherapy
Primary GCSF treatment may be warranted in high-risk patient populations where the incidence of
febrile neutropenia (FN) is at least 40%
•
•
•
•
•
•
In patients with diffuse aggressive lymphoma aged > 65 years
Pre-existing neutropenia
Extensive prior chemotherapy
Previous irradiation to the pelvis or other areas containing large amounts of bone marrow
A history of recurrent febrile neutropenia while receiving earlier chemotherapy of similar or lesser
dose
Conditions that potentially enhance the risk of serious infection (Poor performance status, active
infection, decreased immune function)
Secondary prophylaxis
Adjunctive prophylaxis
Secondary
use
This evidence
The
was proposed
suggests
as athat
treatment
GCSF’s for
should
patients
not be
who
used
have
routinely
had an episode
as adjunctive
of febrile
therapy
neutropenia
to antibiotics
with in
a
patients with
previous
course
uncomplicated
of chemotherapy.
febrileThe
neutropenia
patient would
(FN) be
of duration
able to continue
<10 dayswith
or afebrile
the equivalent
neutropenia.
chemotherapy dose or not have significant treatment delays if used.
However, the ASCO guidelines suggest that the use of GCSF’s should be considered in patients at high
risk of infection
Possible
clinical contexts
associated
forcomplications
secondary prevention
and adverse
might
prognostic
include factors, such as those with Adjuvant
•chemotherapy
Adjuvant chemotherapy
• Chemotherapy
Profound neutropenia
for germ
(ANC
cell <tumours
0.1x10e9/L)
• Elderly
Pneumonia
patients with high grade NHL
• Dose
Hypotension
escalated or intensive schedules for Hodgkin’s and Non-Hodgkin’s lymphoma
• AML
Multifollowing
organ dysfunction
consolidation
(sepsis
treatment
syndrome)
• AML
Invasive
following
fungal induction
infection treatment if appropriate to reduce hospital stay and antibiotic use
• ALL
Elderly
following
patients
intensive
>65 years
phases
or those
of therapy
with post-treatment lymphopenia
• In
Expected
patientsprolonged
who haveduration
previously
of experienced
neutropenia episodes
>10 days of complicated neutropenia
With chemotherapy
Acute Myeloid Leukemia
(AML)
The routine use of CSF is recommended
after consolidation chemotherapy (level
Ib, Grade A). CSF is recommended after
induction if it is appropriate to reduce
hospital stay or antibiotic usage.
Acute Lymphoblastic
Leukemia (ALL)
Myelodysplastic Syndrome
(MDS)
GCSF is indicated to reduce the severity
of neutropenia following intensive
phases of therapy (level Ib, grade A).
CSF’s are indicted to reduce the severity
of neutropenia in patients receiving
intensive chemotherapy (level Ib, grade
A). CSF’s are also recommended on an
intermittent basis for patients with
neutropenia and infection (level IV,
grade C), but continuous prophylactic
use is not routinely justified.
With chemotherapy
Aplastic anaemia
There is insufficient evidence to make
any general recommendations and
hence patients should be given CSF’s
only on an individual therapeutic trial
basis (level IV, grade C).
Bone marrow failure
syndromes
Malignant lymphomas
GCSF is recommended when
improvement of neutrophil count is
appropriate (level III, grade B).
There is evidence to support the
routine use of CSF’s to reduce the
incidence of infection, chemotherapy
delay and hospitalization especially
when the risk of febrile neutropenia
exceeds 40% (level Ia, grade A). There is
also emerging evidence of improved
survival with GCSF-supported dose
intensification in elderly patients with
high-grade NHL (level Ib, grade A). At
present, this evidence is insufficient to
justify a change in policy in all patients
with lymphoma, but elderly patients
may benefit from G-CSF support.
Mobilisation
• G-CSF’s are recommended by the BSCH for the mobilisation of
peripheral blood progenitor cells (PBPC)
• Dose is calculated by weight; reference tables are available in
Mount Vernon Guidelines 2010.
• GCSF can be used alone or in conjunction with chemotherapy.
• Biosimilars not recommended by EBMT 2011
GCSF manufacturers
•
Neupogen/Filgrastim
Granocyte/Lenograstim
Although pharmacologically
equivalent, there is a slight
Original
Neulasta
Nivestim
Zarzio
Amgen
produce
by cell derived GCSF
Chugai
produce
by CHO
synthesis
difference between
e-coli
and
Original
Biosimilar
recombinant
technology:
The
in Chinese Hamster
Ovary
Amgen
produce
viavia
the
e-coli
Sandoz
Hospira
produce
the
epharmacokinetically
human
inserted
(CHO)GCSF
cells,gene
this is
process
method
coli
method
into
an e-coli
bacteria which
makes
it indistinguishable
in from
turn
produces
GCSF
human GCSF
http://www.neulasta.com/
http://www.nivestim.eu/
http://www.zarzio.com/
http://www.neupogen.com/
http://www.chugai-pharm.co.uk/products
How to administer…
GRANOCYTE
Instructions
GRANOCYTE
Instructions
GRANOCYTE
Instructions
GRANOCYTE
Instructions
NEUPOGEN
Instructions
How do I prepare my Neupogen injection?
Before you inject Neupogen you must do the following:
1 To avoid bending the needle, gently pull the
cover from the needle without twisting as shown
in pictures 1 and 2.
2 Do not touch the needle or push the plunger.
• You may notice a small air bubble in the pre-filled syringe.
• You do not have to remove the air bubble before injecting.
Injecting the solution with the air bubble is harmless.
3 You can now use the pre-filled syringe.
The best places to inject are the top of your
thighs and the abdomen. If someone else is
injecting you, they can also use the back of your
arms.
You may change the injection site if you notice
the area is red or sore.
NEULASTA
Instructions
NEULASTA
Instructions
NEULASTA
Instructions
NEULASTA
Instructions
NIVESTIM
Instructions
NIVESTIM
Instructions
NIVESTIM
Instructions
ZARZIO
Instructions
ZARZIO
Instructions
ZARZIO
Instructions
GCSF Common Side Effects
Bone pain
Red itchy skin
Fluid retention
Fever and chills
Plerixafor
• Originally for HIV and manufactured by Genzyme
• Works as a HSC mobiliser
• Licensed for lymphoma and myeloma poor mobilisers in
conjunction with GCSF
Dose
Plerixafor (Mozibil™) ADULT over 18 years, 240 micrograms/kg daily 6-11 hours before initiation of apheresis; usual duration 2-4
days (max. 7 days) by subcutaneous injection. Mozobil injection supplied as 1.2mL-vial
Indications
Peripheral Blood Stem Cell Mobilisation, with GCSF in patients with Lymphoma or Myeloma
Instructions for injecting Plerixafor
You will most likely receive your Plerixafor injections at your transplant center or hospital, depending on hours of operation.
Plerixafor will be given to you as an injection under your skin (this is called a subcutaneous injection).
A member of your healthcare team will inject the medication into a fleshy part of your body (such as your hip or leg).
Plerixafor is given in combination with GCSF. Your doses of GCSF should be given each day starting 4 days before your first evening
dose of Plerixafor and every morning you are scheduled for a session of apheresis.
Thank you