Growth factor: GCSF 10µg/kg/day (same dose for adults and children).
Informed consent and counselling of a healthy donor must be done by a healthcare professional who is not directly involved in the care of the recipient of the donation.
Mandatory microbiology screening tests must be carried out for all donors (table below).
Healthy donors should be mobilised with non-biosimilars only.
Maximal blood volume 24L collected over 1-2 days.
CD34+ check: start on D4
Apheresis should not be performed when CD34+ cell count <5/µL.
Start apheresis when peripheral blood CD34+ cell count >10/µL.
Target collection: minimum 2 x 106CD34+ cells/kg.
Higher doses result in faster engraftment, reduced TRM and possibly reduced relapse risk.
No benefit beyond a certain threshold (8 – 9.5 x 106 CD34+ cells/kg), likely increased risk of chronic GVHD.
Target of 4 – 5 x 106CD34+ cells/kg probably reasonable.
Most cell separators default to two blood volumes.
Access: peripheral venous access is acceptable if adequate flow rates can be achieved. Otherwise, central line placement is required.
Safety: unrelated donors should not undergo leukapheresis for more than 2 days.
There is a risk of thrombocytopaenia due to the inability to completely separate platelets from the target cell layer.
The safety of continuing leukapheresis must be reviewed if plt <100×109/L.
Splenic rupture risk (general practice, not evidence-based):
Withhold GCSF when WBC >100×109/L.
Withhold plerixafor when WBC >75×109/L.
Other risks of apheresis:
Citrate toxicity: hypocalcaemia and low magnesium, with risk of neurological symptoms and arrhythmias.
Thrombocytopaenia from platelet loss in the collected fraction.
Vasovagal reactions (ACE inhibitors increase this risk for all apheresis procedures, hence all patients on an ACE inhibitor should omit it the day of the apheresis procedure).
These are therapeutic T cells from the original donor, which can be used to treat mixed chimerism or minimal residual disease following allogeneic SCT.
Collection is via a standard mononuclear clear cell collection procedure, using two or three blood volumes.
Autologous Stem Cell Transplant
Growth factor: GCSF 10µg/kg/day or pegfilgrastim 12mg single SC dose.
Chemotherapy + growth factor: GCSF 5-10µg/kg/day or pegfilgrastim 12mg single SC dose, start leukapheresis when peripheral blood CD34+ cell count adequate.
In the absence of specific protocol-driven chemotherapy, mobilisation with cyclophosphamide or etoposide results in higher collection yields and fewer aphersis days than growth factor alone.
CD34+ check:
Growth factor alone: start on D4
Chemotherapy + growth factor: start on D8-10 of chemotherapy (peak is usually protocol specific, however)
Growth factor + plerixafor: start on D4
Start apheresis when peripheral blood CD34+ cell count >5-20/µL (locally in NUH, we start at 10/µL).
UK recommendation: start collection when peripheral blood CD34+ cell count >10/µL.
Target collection: minimum 2 x 106CD34+ cells/kg, optimal number > 5 x 106CD34+ cells/kg.
Super mobilisers (>8 x 106 CD34+ cells/kg) associated with faster haematopoietic recovery, more robust long-term platelet recovery and improved overall survival.
Apheresis volumes range from standard lower-volume (10-15L, 2-3 blood volumes based on a blood volume calculation of 70ml/kg) procedures to large volume procedures (15-30L, 3-6 blood volumes).
Large volume collection (at least 3 blood volumes) is associated with increased CD34+ yields, and should be considered for poor mobilisers (CD34+ <20/µL).
However, the larger the collection volume, the larger the risk of apheresis:
Citrate toxicity: hypocalcaemia and low magnesium, with risk of neurological symptoms and arrhythmias.
Thrombocytopaenia from platelet loss in the collected fraction.
Coagulopathy from dilution of coagulation factors.
Extending aphersis beyond 4 days is rarely successful.
Factors which predict poor mobilisation:
Age >60
Diagnosis of non-Hodgkin lymphoma
Multiple prior lines of chemotherapy
Prior exposure to alkylating agents
Prior exposure to purine analogues
Prior exposure to radiotherapy
Prior exposure to lenalidomide
Platelet count <100×109/L
Low prer-apheresis CD34+ cell count
Poor CD34+ cell count (<1×106/kg) on the first day of collection
Previous mobilisation failure
Potential rescue therapy for poor mobilisers:
Increase GCSF dose to 20-30µg/kg/day if not ready for collection by D12-13.
D12 or 13 rescue dose of plerixafor.
Splenic rupture risk (general practice, not evidence-based):
Withhold GCSF when WBC >100×109/L.
Withhold plerixafor when WBC >75×109/L.
Monitoring (pre- and post-procedure):
Electrolytes
Coagulation profile
FBC
Transfusions should be carried out before or after apheresis, not during the procedure.
Plerixafor
Up to 30% of patients fail to mobilise with GCSF+chemotherapy alone.
Failure rates for second mobilisation attempts are in excess of 70%.
Plerixafor is a CXCR4 antagonist, which results in mobilisation of CD34+ stem cells into the peripheral blood.
European licensing: in combination with GCSF to enhance mobilisation in lymphoma / myeloma patients who mobilise poorly.
Strategies for plerixafor use:
Delayed remobilisation: use after a prior failed mobilisation.
Requires re-scheduling of ASCT and waiting 4 weeks for marrow recovery.
Preemptive use (UK recommendation): in the course of a mobilisation episode to improve harvest results when a standard mobilisation is predicted to fail (“rescue” or “just-in-time” use).
Upfront: plerixafor in combination with GCSF for all patients.
Delayed remobilisation: G-CSF 10µ/kg/day for 4 days, then plerixafor, GCSF+plerixafor can be continued daily with an aphersis session after each dose of plerixafor, up to a maximum of 7 days (60% NHL, 71% myeloma, 77% Hodgkin lymphoma achieved target cell dose of 2×106 CD34+ cells/kg).
Upfront: G-CSF 10µ/kg/day for 4 days, then plerixafor (59% NHL and 72% myeloma achieved target dose of 5×106 CD34+ cells/kg). Upfront plerixafor is not currently reimbursed by the NHS.
Preemptive:
Chemomobilisation: give plerixafor if peripheral CD34+ cell count <15/µL and once WBC >4×109/L.
GCSF mobilisation: give plerixafor if peripheral CD34+ cell count <15/µL after 4 days.
Plerixafor can also be given if the day 1 apheresis yield is <1×106/kg.
Currently, UK consensus is that there is no minimum CD34+ count at which plerixafor should be avoided (some argue that it should not be given if CD34+ <5/µL for fear of futility).
When to stop plerixafor:
If a patient’s CD34+ cell count has not risen to >10/µL after an initial dose of plerixafor.
No more than 3-4 doses of plerixafor should be given.
Plerixafor is capable of inducing successful second PBSC attempts, even if preemptive therapy fails. Hence, if plerixafor does not result in successful PBSC collection during initial mobilisation attempts, then a second mobilisation attempt (either chemomobilisation or GCSF alone) incorporating plerixafor is appropriate.
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