Stem cell mobilisation and collection in Glasgow including the use of plerixafor Joy Sinclair Nurse Manager Clinical Apheresis Unit SNBTS, Glasgow.

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