Stem cell mobilisation and collection in Glasgow including the use of plerixafor Joy Sinclair Nurse...
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Transcript of Stem cell mobilisation and collection in Glasgow including the use of plerixafor Joy Sinclair Nurse...
Stem cell mobilisation and collection in
Glasgow including the use of plerixafor
Joy SinclairNurse ManagerClinical 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 post-dose. (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 ‘immediate-rescue’ 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 ‘pre-collection 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
PlerixaforCriteria 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 l Patient must be infection free
There is some published evidence that giving plerixafor in patients with
WBC above 20 also works
PlerixaforCollection 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 considerationsGeneral
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 considerationsCobe 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 considerationsSpectra 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 considerationsSpectra 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