Transcript Stem cell mobilisation and collection in Glasgow

Stem cell mobilisation and collection in
Glasgow including the use of plerixafor
Joy Sinclair
Nurse Manager
Clinical Apheresis Unit
SNBTS, Glasgow
Background on the Clinical
Apheresis Service
in Glasgow
 Department set up in the
early 1990’s
 Specifically for apheresis
procedures
 Performed 1500
procedures 2010- 2011
 Peripatetic Service
 Currently 6 members of
nursing staff
Background on the Clinical
Apheresis Service
in Glasgow
 1100 Therapeutic Plasma Exchange Procedures
(TPE)
 Around 400 mobile procedures
 160 Extra Corporeal Photopheresis (ECP)
 20 Red Blood Cell Exchange (RBCX)
 175 Peripheral Blood Stem Cell Collection (HPC-A)
 150 Autologous
 25 Allogeneic
 Use COBE Spectra and Spectra Optia
Objectives
 Timing of mobilisation
 Plerixafor
 Planned use
 Rescue
 The Collection
 Procedural considerations
 COBE Spectra
 Spectra Optia
Timing of Mobilisation
 No weekend processing facility
 In an unusual situation we can
collect on a Sunday
 Chart based on historical
departmental data
 Shared with 50 referring
haematologists throughout
West of Scotland
 Encouraged to contact CAU to
confirm dates
 Patient Appointment
 Biggest challenge - paediatrics
Tuesday
Mechanism of Action – G-CSF

Haematopoietic stem cells are held in the bone marrow by using the chemokine receptor
CXCR4 to look for/ identify a “homing” signal from the chemokine SDF1 (Stromal Derived
Factor).

They are also “tethered” to osteoblasts (bone progenitor cells) by cell adhesion proteins such
as VCAM.

GCSF stimulates the production of neutrophils in the bone marrow, which in turn increases the
number of WBCs in the blood. However, as part of this process the bone marrow can get
packed out with neutrophils.

Neutrophils naturally produce protease enzymes including elastase. At high levels these can
break down SDF1 (which is a small protein) and therefore reduce the “homing” signal for
stem cells. Neutrophil proteases can also break down cell adhesion proteins like VCAM and
release stem cells from their normal “tethers”.

With the lack of SDF1 and breakdown of VCAM, the stem cells will come out of quiescence
in the bone marrow and migrate into the blood giving us the opportunity of collecting them on a
cell separator.
Mechanism of Action - Plerixafor
 Plerixafor has a different mechanism of action in that it
directly works at the CXCR4 receptor by blocking
it. The stem cells therefore do not have the ability to
detect the presence of SDF1 and will again come out
of quiescence and migrate into the blood giving the
opportunity to collect them on a cell separator
 Evidence at the moment suggests plerixafor works
well combined with G-CSF.
Plerixafor - Approval
 Scottish Medicines Consortium approval for
plerixafor
 Approval of plerixafor by the SMC allows the drug to
be prescribed routinely by NHS Scotland for its
licensed indications on the advice of an Oncologist or
Haematologist
 Approved in combination with G-CSF for PBSC
mobilisation for Myeloma or lymphoma patients
whose cells mobilised poorly
 This allows the drug to be used on a remobilisation
basis and on an immediate rescue basis
Plerixafor- Planned re-mobilisation
 Wait 4 weeks to allow the patient’s
marrow to recover
 Re-mobilise patient with G-CSF 10
micrograms/kg/day for 4 days &
plerixafor on evening of day 4
 Apheresis morning of day 5
 Repeat G-CSF, plerixafor and apheresis
daily until enough cells are collected
Plerixafor - Planned re-mobilisation
 Avoid weekend procedures by planning day 1 G-CSF on a Friday.
First dose plerixafor will be due on Monday which will give 4 days
available to collect PBSC
 Plerixafor can be given as an out-patient in the late evening (9.30
pm). Well-motivated patients may safely self-administer.
 Timing of collection is important: guidance from Genzyme in
plerixafor package insert suggests starting apheresis 11 hours postdose. (Our practice is to start at 9 am, 11-12 hours post dose)
 Consider large volume apheresis
 Don’t wait on peripheral CD34+ count
Plerixafor - Planned re-mobilisation
 Advantages
 Timing for apheresis is
predictable
 Successful for most
patients with a average of
2 doses of plerixafor
 Time to organise and
plan both for the staff and
patient
 Disadvantages
 Delay in collecting the
cells
 PBSC on a high WCC so
product is more cellular
leading to high
cryopreservation volumes
and more DMSO
 Theoretical danger of
hyperleucocytosis
 Probably less cost
effective than ‘immediaterescue’ use
Plerixafor - Immediate-rescue
 Patient receives mobilising chemotherapy as planned
 WCC and peripheral CD34 count check on predicted
day of mobilisation
 If neutrophils are recovered but CD34 count low
plerixafor can be given that evening
 G-CSF given at 7am the following morning
 Apheresis commenced at 9 am
 GCSF, plerixafor and apheresis repeated daily until
patient has enough cells
Plerixafor - Immediate-rescue
 Advantages
 Cost effective. Some patients
predicted to mobilise poorly
may do OK by conventional
means
 No need for the patient to come
back and go through the ‘precollection process’ again
 No transplant delay for the
patient
 Fewer plerixafor doses required
to achieve transplantable cell
dose in our experience (1.4
doses)
 The collection is usually done
on a lower WCC so less
cryopreservation issues
 Disadvantages
 Plerixafor toxicities maybe
higher if added to pre exisiting
toxicities of chemo esp. GI
toxicities
 Not as predictable for apheresis
scheduling
 Potential problem with ideal
collection time over the
weekend
 Logistics for staff and patients
organising process at the last
minute (ordering, prescription,
late night injection, early
morning G-CSF and apheresis)
 It’s a great deal of information
for the patients with little time to
digest
Plerixafor - Approved Protocol
 We have an approved protocol for
plerixafor use in the West of
Scotland
 This allows re-mobilisation with
plerixafor for myeloma and
lymphoma patients.
 It also allows immediate rescue if the
patient meets certain criteria
Plerixafor
Criteria for Immediate-Rescue
 Must be a definite date for transplant
 Must be no more than 1 day before
anticipated date of first mobilisation
 Total WBC on first plerixafor day must be
at least 4.0 x 109/l but less than
20 x109/l
 Peripheral CD34 count must be less than
15 per ml
 Patient must be infection free
There is some published evidence
that giving plerixafor in patients with
WBC above 20 also works
Plerixafor
Collection Considerations
 Change in goal posts now looking for minimum
transplant dose (Glasgow 2.5 x 106 kg) but higher doses
may be possible
 Consider collecting the patients stem cells 11 hours post
plerixafor without waiting for a CD34 count.
 Consider a large volume apheresis to work towards
achieving transplant dose (3xTBV)
 Ensure good venous access
 Consider if second dose of
plerixafor required or if G-CSF
may be enough
The Collection
 We use both Spectra Optia and Cobe Spectra
for collection
 Cobe Spectra
 Data over 5 years 500 procedures
 Efficiency is 50% (CE2)
 Spectra Optia
 Data over 1 year – 100 procedures
 Efficiency is 55% (CE2)
Procedural considerations
General
 Consider a large volume apheresis
to work towards achieving transplant
dose (3xTBV)
 Consider a high flow procedure to
process more cells per minute
 Remember increasing flow rate will
increase AC infusion rate to the
patient.
 Consider using IV calcium
gluconate/chloride
 Consider increasing AC ratio. This
allows you to process faster but with
the same AC infusion rate to the
patient (max 15:1)
Procedural considerations
Cobe Spectra
 Spectra - consider
increasing the collect flow to
1.1 or 1.2 if WBC count above
40 (calculation tool on
CaridianBCT web site)
 Spectra – consider collecting
at 3.5 – 5% Hct. This
maximises mononuclear cell
collection but also will
increase RBC and
granulocyte contamination
Procedural considerations
Spectra Optia
Optia collects a purer product than
Spectra and eliminates problematic
high cryopreservation volumes seen
with Spectra collections on high WBC
count’s.
This is particularly useful for patients
mobilised with plerixafor where high
WBC levels are likely.
Procedural considerations
Spectra Optia
 Optimization guide from CaridianBCT
 Set default value of the chamber
chase to 4 mls
 Aim for 750-1250ml inlet volume
processed per chamber
 WBC > 20 start or change to a
collection preference (CP) of 20
 WBC < 10 start or change to a
collection preference (CP) of 60
 Consider use of inlet Volume control
In summary
 Glasgow annual Autologous HPC-A procedure
numbers are between 150 – 200
 Until 2008 10-15% failure rate in mobilisation
 Since 2008 with the introduction of plerixafor
we have had a 100% success rate in collecting
a transplantable dose
 Average of 1.5 procedures to collect a
transplantable dose (Min 2.5 CD34 x 106, Max
6 CD34 x 106)
 Consideration should be given to optimizing the
collection tailored to individual situations
 Spectra Optia is as efficient if not more efficient
than Cobe Spectra