Download Haematopoietic Stem Cell Mobilisation and Apheresis:

Haematopoietic Stem Cell
Mobilisation and Apheresis:
A Practical Guide for
Nurses and Other Allied
Health Care Professionals
I
The European Group for Blood and Marrow Transplantation
gratefully acknowledges the following individuals for their
critical review and contributions to this guide:
Erik Aerts (RN) Switzerland
Aleksandra Babic (RN) Italy
Hollie Devine (RN) USA
Francoise Kerache (RN) Germany
Arno Mank (RN) Netherlands
Harry Schouten (MD) Netherlands
Nina Worel (MD) Austria
Haematopoietic Stem Cell
Mobilisation and Apheresis:
A Practical Guide for Nurses and Other
Allied Health Care Professionals
Table of Contents
Chapter 1: Overview of Autologous Haematopoietic Stem Cell Transplantation. . . . . . . . . . . . . . . 1
Chapter 2: Mobilisation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Chapter 3: Stem Cell Collection (Apheresis), Storage, and Reinfusion. . . . . . . . . . . . . . . . . . . . . 13
Chapter 4: How to Discuss Noted Topics With Patients. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Additional Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Notes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Table of Contents
Chapter 1: Overview
Chapter 1:
Overview of Autologous Haematopoietic Stem Cell Transplantation
Widely accepted cancer treatment strategies include chemotherapy and radiotherapy. The rationale for
administration of high-dose chemotherapy and/or radiation to patients with therapy-sensitive tumours is to
reduce tumour burden. Delivery of these therapies with respect to higher drug doses and intensified schedule
are often limited by organ toxicities (eg, bone marrow, heart, and lung) and pancytopenia. To overcome
these dose limitations, autologous haematopoietic stem cell transplantation (AHSCT), high-dose
therapy supported by the infusion of haematopoietic stem cells, has evolved as a medical procedure to allow for
administration of intense drug doses with tolerable organ and haematopoietic toxicity. Infusion of autologous
stem cells following dose-intensive treatment “rescues” the bone marrow by re-establishing normal
haematopoiesis. Upon regeneration of bone marrow function, patients may be cured from their disease or
receive additional cancer treatment.1,2
Autologous haematopoietic stem cell transplantation is a complex medical procedure that has been used to
treat and cure patients with various malignant and non-malignant disorders. Although the first documentation of
AHSCT use to treat cancer was reported in the 1890s,3 achievement of a cure in patients with a malignancy was
only documented in 1978 following a clinical trial conducted at the National Cancer Institute (United States).4
Subsequent to this report, numerous advances have been made in the art of AHSCT and thousands of patients
around the world have had their diseases successfully managed through the use of AHSCT.
The term “autologous haematopoietic stem cell transplantation” is frequently used interchangeably with the
terms autologous bone marrow transplantation (aBMT), autologous peripheral blood stem cell transplantation
(aPBSCT), and autologous haematopoietic cell transplantation (AHCT).5 “Autologous” means that the donor cells
used for the procedure are from the patient himself, as opposed to “allogeneic,” which refers to a cell donor
other than the patient. In certain allogeneic circumstances, the term “syngeneic” is used when the cell donor
is a patient’s identical twin. The source of stem cells for collection is identified by the terms “bone marrow” and
“peripheral blood.” Cells for the patient may be collected either from the donor’s bone marrow reserves, such
as those stored in the iliac crest of the pelvic bones, or from the donor’s peripheral blood. Additionally, umbilical
cord blood (UCB), found in the umbilical cord and placenta following childbirth, is another source of progenitor
stem cells used in clinical practice in the setting of allogeneic transplants.6 When 2 autologous stem cell
transplantations occur in a scheduled, sequential fashion, this process is referred to as “tandem autologous
stem cell transplantation.”6,7
In the more than 3 decades following the first successful use of AHSCT, the utility of this treatment for malignant
and non-malignant conditions has been well established (Table 1).8 In the setting of relapsed malignant
conditions, standard chemotherapy regimens may produce unacceptable rates of bone marrow suppression
(myelosuppression), resulting in a low white cell count, low platelet count, and anaemia. This increases the
risk of potentially fatal infections and bleeds. Following chemotherapy, the patient is therefore given a transplant
of stem cells to regenerate damaged bone marrow. Thus, the reinfusion of autologous stem cells has become a
therapeutic modality for reducing prolonged myelosuppression.9-11 Data demonstrate that high-dose therapy with
stem cell rescue has a positive impact on disease response rates; however, for some patients it fails to improve
overall survival when compared to conventional chemotherapy treatments. Thus, the definitive role of AHSCT in
certain situations, such as the treatment of refractory or relapsed Hodgkin’s lymphoma or chronic lymphocytic
leukaemia, remains inconclusive12-15 and indications for AHSCT continue to evolve.
Chapter 1: Overview of Autologous Haematopoietic Stem Cell Transplantation
1
Table 1. Indications for Autologous Haematopoietic Stem Cell Transplantation in Adults8
Disease
Standard of Care
Optional Based on
Risks and Benefits
Acute lymphoid
leukaemia
Acute myeloid
leukaemia
CR1 (intermediate risk)
M3 (molecular CR2)
Chronic lymphoid
leukaemia
Chronic myeloid leukaemia
Investigational or
Additional Trials
Needed
CR1 (standard,
intermediate or high risk)
CR1 (low or high risk)
CR2
Poor risk disease
First (CP), failing imatinib
Accelerated phase or >
first CP
Myelodysplastic
syndrome
Chemosensitive relapse;
≥ CR2
Mantle cell
lymphoma
CR1
Chemosensitive relapse;
≥ CR2
Chemosensitive relapse;
≥ CR2
T-cell NHL
Lymphocyte predominant
nodular Hodgkin’s
lymphoma
Multiple myeloma
Chemosensitive relapse;
≥ CR2
Ovarian cancer
Medulloblastoma*
CR1 (intermediate or high
IPI at diagnosis)
Refractory disease
CR1
Chemosensitive relapse;
≥ CR2
CR1 (intermediate or high
IPI at diagnosis)
CR1
Refractory disease
Refractory disease
Chemosensitive relapse;
≥ CR2
Refractory disease
Refractory disease
CR1
Chemosensitive relapse;
≥ CR2
Refractory disease
CR1

Amyloidosis
Severe aplastic anaemia
Paroxysmal nocturnal
haemoglobinuria
Breast cancer*
Germ cell tumours
Blast crisis
Primary or secondary with an
intermediate or high Lille score
RA
RAEB
More advanced stages
Refractory disease
RAEBt
sAML in CR1 or CR2
Diffuse large
B-cell NHL
Hodgkin’s lymphoma
CR2 (incipient relapse)
Relapsed or refractory disease
CR3 (incipient relapse)
M3 (molecular persistence)
Relapsed or refractory disease
Myelofibrosis
Lymphoblastic
lymphoma and
Burkitt’s lymphoma
Follicular B-cell NHL
Generally Not
Recommended



Third-line refractory
Adjuvant high risk disease
Metastatic responding
Sensitive relapses
Post-surgery
Small cell lung cancer
Metastatic
responding
CR/PR
Post-surgery
Platinum-sensitive relapse
Limited disease
Renal cell carcinoma
Metastatic, cytokine-refractory
Soft cell sarcoma
Metastatic, responding
Immune cytopenias

Systemic sclerosis

Rheumatoid arthritis

Multiple sclerosis

Systemic lupus

erythematosus
Crohn’s disease

Chronic inflammatory

demyelinating
polyradiculoneuropathy
CP, chronic phase; CR1, 2, 3, first, second, or third complete remission; CR/PR, complete response/partial response; IPI, International
Prognostic Index; NHL, non-Hodgkin’s lymphoma; RA, refractory anaemia; RAEB, refractory anaemia with excess blasts; RAEBt,
refractory anaemia with excess blasts in transformation; sAML, secondary acute myelogenous leukaemia;  indicates use of autologous
haematopoietic stem cell transplantation regardless of stage.
* For patients with metastatic responding breast cancer or medulloblastoma, autologous haematopoietic stem cell transplantation can be
considered when the benefits outweigh the risks, although additional studies are warranted.
2
Haematopoietic Stem Cell Mobilisation and Apheresis:
A Practical Guide for Nurses and Other Allied Health Care Professionals
An AHSCT is a complex process involving a multidisciplinary approach and resource utilisation. Historically,
this treatment was offered only at large academic medical centres. However, due to medical progress and our
knowledge of the AHSCT procedure, patients are receiving this therapy in community settings. The stem cell
transplant process can be summarised in 8 distinct phases (Figure 1): (1) administration of mobilisation
agents, (2) mobilisation, (3) collection, (4) preparation of product for storage, (5) cryopreservation, (6)
administration of preparative regimen, (7) stem cell transplantation, and 8) engraftment and recovery.1,2,6,16
For a more detailed explanation of each phase, please see Chapter 3.
Figure 1. The Stem Cell Transplant Process1,2,6,16
Injections
1
Injections of mobilisation agents
4
Preparation for Storage
Stem cells collected are stored in infusion bags
7
Stem Cell Transplant
Previously collected stem cells are thawed and infused
back into the bloodstream
2
Mobilisation
Stem cells are stimulated to move into the
bloodstream from the bone marrow space
5
Cryopreservation
Freezing of stem cells for use after completion of
preparative regimen
8
3
Collection
Collection of mobilised stem cells from the blood
using the apheresis machine
6
Chemotherapy
and/or Radiation
Administration of preparative regimen intended to
kill any remaining cancer cells and make a space for
new cells to live
Engraftment and Recovery
One aim of autologous stem cell transplant is for infused stem cells to mature into functional blood components such as neutrophils
and platelets. The first signs of engraftment and recovery include increasing absolute neutrophil and platelet counts
Chapter 1: Overview of Autologous Haematopoietic Stem Cell Transplantation
3
Once patients are identified as being candidates for AHSCT, they undergo detailed evaluations to ensure that they
will be able to tolerate the procedure. Patients are administered exogenous agents to stimulate the migration
of progenitor cells from the bone marrow into the peripheral blood. Procurement of these cells is achieved by
apheresis. At the conclusion of apheresis, cells are processed and cryopreserved for future use. Product
storage time is typically a few weeks to months, although some investigators have reported storing product
for up to 14 years without loss of product viability.17-19 Following apheresis, patients may receive additional
chemotherapy to treat their underlying disease or proceed directly to receiving a transplant preparative regimen
(ie, high dose chemotherapy ± radiotherapy) followed by infusion of previously collected stem cells. The first
signs of engraftment, indicated by an increase in white blood cell (WBC) counts, usually occur within 2 to 4
weeks following the infusion of autologous stem cells.1,2
4
Haematopoietic Stem Cell Mobilisation and Apheresis:
A Practical Guide for Nurses and Other Allied Health Care Professionals
Chapter 2: Mobilisation
Haematopoiesis refers to the production of cellular components of blood. This process occurs continually to
maintain normal immune system function and haemostasis. In adults, haematopoiesis primarily occurs in the
bone marrow that is contained within the pelvis, sternum, vertebral column, and skull.20,21 Production of mature
blood cells specifically occurs in the bone marrow microenvironment (Figure 2).20-22
Chapter 2: Mobilisation
Figure 2. Bone Marrow Microenvironment20-22
All blood cells are derived from progenitor stem cells, also referred to as pluripotent stem cells. These cells
have the capacity for unlimited self-renewal and the ability to differentiate into all types of mature blood cells.
The pluripotent stem cell can differentiate into 1 of 2 types of common progenitor cells—the common myeloid
progenitor and the common lymphoid progenitor. These common progenitor cells can further differentiate
into committed cellular components through an intricate cascade of events (Figure 3). The end result is the
production of cells in the myeloid lineage and the lymphoid lineage. Cells in the myeloid lineage, such as red
blood cells, platelets, macrophages, and neutrophils are responsible for tissue nourishment, oxygenation, blood
viscosity, coagulation, and immune function such as innate and adaptive immunity. The lymphoid lineage
components, namely T cells and B cells, provide the foundation for the adaptive immune system.2,20
Cytokines play an integral role in haematopoiesis. When progenitor cells are exposed to cytokines, the
maturation cascade to produce committed mature blood cell components can occur. Examples of important
cytokines are listed in Figure 3. These cytokines are found endogenously, although during the stem cell collection
process, some are often exogenously administered to patients in an effort to enhance the yield of stem
cells within a short time period.21-25 Examples of these exogenous cytokines include filgrastim (glycosylated
granulocyte colony-stimulating factor [G-CSF]) and lenograstim (non-glycosylated G-CSF).
Chapter 2: Mobilisation
5
Figure 3. Stem Cell Maturation Cascade2,20
Epo, erythropoietin; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor;
IL, interleukin; M-CSF, macrophage colony-stimulating factor; SCF, stem cell factor; Tpo, thrombopoietin.
Chemokines are a subset of cytokines associated with a single receptor and assist in cell movement.
Stromal cells are layers of cells that support the bone marrow microenvironment. These cells produce the
chemokine stem cell derived factor-1 alpha (SDF-1α). This chemokine is an important signalling molecule involved
in the proliferation, homing, and engraftment of stem cells. For a given time in their development, stem cells
express the chemokine receptor CXCR4. CXCR4 is responsible for anchoring stem cells to the bone marrow
microenvironment. When CXCR4 and SDF-1α bind, interactions between integrins and cell adhesion molecules
also occur. The anchoring of stem cells within the bone marrow microenvironment occurs by continuous
production of SDF-1α by stromal cells. It is the loss of attachment to the stromal cells, along with the loss of
SDF-1α activity, that favours the release of stem cells into peripheral circulation. Blockade of this receptor with
a chemokine antagonist (such as plerixafor) has elevated circulating haematopoietic stem cells (HSCs) and aided
stem cell collections in patients with multiple myeloma and lymphoma.26-31
6
Haematopoietic Stem Cell Mobilisation and Apheresis:
A Practical Guide for Nurses and Other Allied Health Care Professionals
Pluripotent stem cells express the cell surface marker antigen CD34. This marker is the indicator most frequently
used in clinical practice to determine the extent and efficiency of peripheral blood stem cell collections.25
Although not a complete measure of the quantity and quality of collected cells, blood samples from collections
are assayed to determine the number of CD34+ cells present. Once specific cell targets are achieved, cell
collections are completed and stored for future use. Standard target levels can vary among treatment centres
and a patient’s specific goal is related to the underlying disease, the source of stem cells, and the type of
transplantation to be performed. In general, a target level of 2 × 106 CD34+ cells/kg body weight is considered
the minimum for autologous transplantation, with optimal levels being ≥ 5 × 106 CD34+ cells/kg for a single
transplant and ≥ 6 × 106 CD34+ cells/kg for a tandem transplant.23,25,32-36
Historically, autologous stem cell collections involved
the removal of bone marrow cells from a patient’s
bilateral posterior iliac crest region (Figure 4) under
general anaesthesia in a hospital operating room.
However, due to advances in medical technology, most
collections today are performed by apheresis (Figure
5). Peripheral blood stem cell collection is considered
the preferred method for mobilisation prior to AHSCT
due to patient convenience, decreased morbidity, and
faster engraftment of WBCs and platelets. Additional
comparisons between harvest of bone marrow and
peripheral blood for autologous transplantation are
summarised in Table 2.1,2,37-40
Figure 4. Bone Marrow Harvest
Table 2. Advantages and Disadvantages of Haematopoietic Stem Cell Collection Methods1,2,37-40
Collection
Method
Advantages
Disadvantages
Bone marrow
• Single collection
• No need for special catheter placement
• Performed in an acute care setting since it
requires general anaesthesia
• Use of cytokines not necessary
• Slower neutrophil and platelet engraftment
• Higher rates of morbidity and mortality
• Potentially more tumour cell contamination of
product
Peripheral
blood
• Does not require general anaesthesia and
can be performed in an outpatient setting
• Faster neutrophil and platelet
engraftment
• Associated with lower rates of morbidity
and mortality
• Collection may take several days
• Sometimes requires placement of large-bore,
double-lumen catheter for collection
• Haemorrhage, embolism, and infection are
possible complications related to insertion of
central venous catheter
• Potentially less tumour cell contamination
of product
Chapter 2: Mobilisation
7
Figure 5. Apheresis Collection
The concentrations of HSCs are 10100 times greater in the bone marrow
compared to the peripheral circulation.1
Therefore, methods to increase the
circulating concentrations of HSCs
are necessary to ensure adequate
and successful collections. Agents
used to mobilise HSCs include the
administration of cytokines with or
without chemotherapy prior to scheduled
collection periods.
Filgrastim and lenograstim used as single-agent mobilisers have been well established, with both agents
having reliably demonstrated increased concentrations of circulating HSCs.41,42 G-CSF is thought to stimulate
HSC mobilisation by decreasing SDF-1α gene expression and protein levels while increasing proteases that
can cleave interactions between HSCs and the bone marrow environment.43-46 The mechanism of action for
G-CSF is illustrated in Figure 6.43-46 The recommended dose of filgrastim and lenograstim is 10 mcg/kg/day as
a subcutaneous injection for multiple days.47,48 However, these growth factors are typically given at a total daily
dosage of 3-24 mcg/kg/day.25 Data indicate that divided doses of G-SCF (eg, lenograstim 5 mcg/kg twice daily)
are more efficacious than single-dose administration (eg, lenograstim 10 mcg/kg once daily) by producing a
higher yield of CD34+ cells and the need for fewer apheresis procedures.49-51 However, current clinical practice
does not favour one schedule over the other.
Figure 6. Mechanism of Action of G-CSF43-46
CXCR4, chemokine receptor 4; G-CSF, granulocyte colony-stimulating factor; SDF-1α, stromal cell derived factor-1 alpha.
8
Haematopoietic Stem Cell Mobilisation and Apheresis:
A Practical Guide for Nurses and Other Allied Health Care Professionals
Since it is common to see an increase in HSCs following recovery from myelosuppressive chemotherapy, another
method to mobilise HSCs involves the administration of chemotherapy, usually in conjunction with cytokines.22,24,25
This is frequently referred to as “chemomobilisation.” Chemotherapy and cytokines work synergistically
to mobilise HSCs, although the exact mechanism for chemotherapy mobilisation has not been fully explained.
Possible mechanisms for mobilisation following chemotherapy include chemotherapy effects on the expression
of cell adhesion molecules in the bone marrow and chemotherapy-induced damage to stromal cells in the bone
marrow. Both of these lead to increased circulating concentrations of HSCs due to disruption of the bone marrow
microenvironment.28 The kinetics of CD34+ cell and WBC production following chemotherapy and growth factor
administration are illustrated in Figure 7.
Figure 7. Generalised Kinetics of Leucocyte and CD34+ Cell
Mobilisation Into the Peripheral Blood Following Chemotherapy
and Cytokine Administration
Chemotherapeutic agents
most commonly used for
chemomobilisation include highdose cyclophosphamide and
etoposide.22,25,38 Filgrastim
(5 mcg/kg/day) can be utilised
as the cytokine partner in
chemomobilisation.47 Because
no single chemotherapy
mobilisation regimen has
demonstrated superiority over
the others, some clinicians
may elect to mobilise patients
during a cycle of a diseasedirected chemotherapy regimen.
Examples of regimens utilised
G-CSF, granulocyte colony-stimulating factor.
include cyclophosphamide,
doxorubicin, vincristine, and prednisone (CHOP) and ifosfamide, carboplatin, and etoposide (ICE).25 Additionally,
the use of rituximab (a monoclonal antibody directed at cells that express CD20) prior to mobilisation
has not demonstrated inferior yields of CD34+ cells; in fact, it may assist with decreasing the amount of
tumour contamination in the collected product.52,53 Adverse events associated with commonly employed
chemotherapeutic agents used in mobilisation regimens are listed in Table 3.54,55
Table 3. Complications* Associated With Chemotherapeutic Agents Commonly Used for
Mobilisation (Like Cyclophosphamide or Etoposide)54,55
Short-Term Side Effects
Long-Term Side Effects
• General malaise (weakness)
• Infertility
• GI symptoms (diarrhoea, nausea, vomiting, appetite loss, stomach discomfort
or pain)
• Skin and mucosal effects (rash, texture change in nails, alopecia, mucositis)
• Myelosuppression (thrombocytopenia, leucopoenia)
• Infusion-related side effects (such as hypotension, flushing, chest pain, fever,
diaphoresis, cyanosis, urticaria, angio-oedema, and bronchospasm)
• Allergic reaction
• Signs of an infection, such as chills or a fever
• Blood in the urine (may be a sign of bladder damage)
• Blood in the stool
• Decreased urination
(may be a sign of kidney
damage)
• Difficulty breathing or
water retention (which
may be signs of congestive
heart failure)
• Secondary malignancies
(may present as unusual
moles, skin sores that
do not heal, or unusual
lumps)
GI, gastrointestinal.
* Please see prescribing information for complete list of adverse reactions.
Chapter 2: Mobilisation
9
Plerixafor is a novel agent that has recently
been approved in the European Union for use
in conjunction with G-CSF in lymphoma and
multiple myeloma patients whose cells mobilise
poorly, to mobilise stem cells from the bone
marrow into the peripheral blood for collection
and autologous transplantation.56 Plerixafor
is a small-molecule CXCR4 antagonist that
reversibly inhibits the interaction between
CXCR4 and SDF-1α (see plerixafor mechanism
of action in Figure 8).57-61 Use of plerixafor in
combination with G-CSF has been shown to
improve CD34+ cell collections in lymphoma
and multiple myeloma patients compared
to G-CSF alone.30,62,63 Very common adverse
reactions associated with the use of filgrastim,
lenograstim, and plerixafor are listed in
Table 4.47,48,56,64
Figure 8. Plerixafor Mechanism of Action57-61
An unfortunate outcome following HSC
collections is poor stem cell yield. The
most important risk factor for inadequate
mobilisation is the amount of myelosuppressive
chemotherapy a patient has received prior to
collection. Agents that are toxic to stem cells,
CXCR4, chemokine receptor 4; SDF-1α, stromal cell derived factor-1 alpha.
2
such as cyclophosphamide (doses > 7.5 g/m ),
melphalan, carmustine, procarbazine, fludarabine, nitrogen mustard, chlorambucil, are particularly detrimental to
stem cell collection yields. Other risk factors associated with low CD34+ cell collections are listed in Table 5.25,65-73
Table 4. Very Common (> 10%) Adverse Reactions* Associated With Agents Used in Stem Cell
Mobilisation47,48,56,64
Agent
Adverse Events
Filgrastim
• Musculoskeletal pain
Lenograstim
•
•
•
•
•
Plerixafor
• Diarrhoea and nausea
• Injection and infusion site reactions
Bone and back pain
Leucocytosis and thrombocytopenia
Transient increases in liver function tests
Elevated LDH
Headache and aesthenia
LDH, lactate dehydrogenase.
* Please see summaries of product characteristics for complete lists of adverse reactions.
10
Haematopoietic Stem Cell Mobilisation and Apheresis:
A Practical Guide for Nurses and Other Allied Health Care Professionals
Table 5. Risk Factors and Characteristics Associated With Poor Autologous Stem Cell
Mobilisation25,65-73
•
•
•
•
•
•
•
•
•
•
Type and amount of chemotherapy administered to patient prior to mobilisation
Advanced age (> 60 years)
Multiple cycles of previous chemotherapy for treatment of underlying disease
Radiation therapy
Short time interval between chemotherapy and mobilisation
Extensive disease burden
Refractory disease
Tumour infiltration of the bone marrow
Prior use of lenalidomide
Evidence of poor marrow function (eg, low platelet and CD34+ cell blood count) at time of mobilisation
Few options exist for patients who mobilise poorly, and standard management of these patients continues to
evolve and remains ill-defined. Currently acceptable strategies for remobilisation involve increasing the doses
of chemotherapy agents and/or cytokines, using a combination of cytokines, and extending the time between
chemotherapy for disease treatment and apheresis. The option of performing a bone marrow harvest to collect
cells is an alternative strategy. However, it is falling out of favour to previously mentioned methods due to
slower engraftment, increased need for resource utilisation (longer hospitalisation and more supportive care
management), and higher risk of mortality.25,35,65,66,74-76 More promising is the use of newer and recently approved
agents (such as plerixafor) as part of established mobilisation techniques to increase stem cell yields during
collections. A comparison between mobilisation methods is listed in Table 6.22,24,25,28,37-39
Table 6. Comparison of Mobilisation Methods22,24,25,28,37-39,77-81 Mobilisation Regimen
Characteristics
Filgrastim or lenograstim
•
•
•
•
•
•
Filgrastim or lenograstim +
chemotherapy
•
•
•
•
•
•
•
•
•
Filgrastim or lenograstim +
plerixafor
•
•
•
•
•
•
•
Low toxicity
Outpatient administration
Can be self-administered
Reasonable efficacy in most patients
Predictable mobilisation, permitting easy apheresis scheduling
Shorter time from administration to collection compared to
growth factor + chemotherapy
• Bone pain
• Lower stem cell yield compared to growth factor + chemotherapy
Higher stem cell yield compared to growth factor alone
Fewer stem cell collections
Potential for anticancer activity
May impair future mobilisation of stem cells
May require hospitalisation
Associated with an increased number of side effects
Inconsistent results
Longer time from administration to collection compared to growth factor
Low predictability of time to peak peripheral blood CD34+ cell levels
Low toxicity
Outpatient administration
Low failure rate
High probability of collecting optimal number of CD34+ cells
Efficacy in poor mobilisers
Predictable mobilisation permitting easy apheresis scheduling
Shorter time from administration to collection compared to
growth factor + chemotherapy
• Gastrointestinal adverse effects
Chapter 2: Mobilisation
11
Chapter 3: Stem Cell Collection (Apheresis), Storage, and Reinfusion
Prior to initiation of the stem cell collection process, patients must be thoroughly evaluated and determined
to be acceptable transplant candidates and able to tolerate all of the procedures involved. Some of the medical,
nursing, and psychosocial evaluations can occur prior to a patient’s first visit or referral to a transplant service
or clinic. The patient’s primary medical haematologist/oncologist frequently serves as a patient’s first contact
during the transplantation process. All of the testing, evaluation, and education involved throughout a patient’s
transplant involves a myriad of health care professionals working together to orchestrate this complex
medical procedure.
The medical pre-evaluation is the first step a patient must complete when undergoing an AHSCT. This involves
the patient’s primary medical oncologist making a referral to a transplant centre or service. The physician provides
the transplant team with information that often includes specifics relating to the care of the patient up to this
time point, such as past medical history, cancer status, summary of cancer treatments and responses, and
complications experienced during therapy. Accompanying this information are any available radiograph and
laboratory testing results.
Chapter 3: Collection,
Storage, and Reinfusion
After review of the patient’s medical information, the transplant team will initiate their own battery of tests and
evaluations to assess a patient’s eligibility to proceed with stem cell collection and transplantation. This involves
restaging the patient to verify or establish current disease status, ascertaining the function of various organs
(eg, kidneys, liver, and lungs), documenting the absence of certain comorbid conditions and infectious diseases
(eg, congestive heart failure and the presence of human immunodeficiency virus), and evaluating the overall
performance status and psychosocial condition of the patient. At this time, extensive education will be initiated
for the patient and their family and/or caregivers. Often a member of the nursing profession (clinic nurse, nurse
educator, or nurse coordinator) will coordinate the education process for the patient and those involved in their
care (see Chapter 4).
Upon determination that a patient is eligible to proceed to transplantation, preparing them for the collection
process occurs next. The preferred method for venous access is the placement of a peripheral catheter at the
time of an apheresis session (eg, insertion into the antecubital vein). For those patients in whom peripheral line
placement is not feasible, appropriate catheter selection and central venous placement (eg, internal jugular
vein) is scheduled prior to the first stem cell collection. Catheters used for apheresis procedures must be able
to tolerate large fluctuations in circulating blood volume. Therefore, these catheters are often large-bore, double
lumen devices that can be used temporarily during cell collections, or placed permanently and used throughout
the transplantation process. As with most catheters placed in the area of the upper extremities, patients should
be monitored for signs and symptoms of hypotension, shortness of breath, and decreased breath sounds as
these can be indicative of venous wall perforation, haemothorax, and/or pneumothorax, all of which are rare
but serious complications that can occur. In some cases, catheters for apheresis may be placed centrally in
a femoral vein if patients are at an increased risk of developing complications from a catheter placed in the
upper extremity or chest wall. For centrally placed catheters, radiographic evaluation is used to verify catheter
placement prior to clearance for its use. Additionally, instructions on caring for the catheter to prevent infection
and maintain its integrity should be extensively reviewed with the patient and/or caregivers.1,2,16,82,83
Preparation for stem cell collections in an apheresis centre or unit follows the pre-transplantation evaluation
and catheter placement. Patients will be advised and counselled on therapies that they will receive during
mobilisation with respect to administration schedule and expected adverse effects. As previously detailed in
Chapter 2, agents used during this stage of AHSCT usually include single-agent cytokines (such as filgrastim)
Chapter 3: Stem Cell Collection (Apheresis), Storage, and Reinfusion
13
that are given with or without certain chemotherapy agents, a designated cycle of disease-specific chemotherapy
regimen, or more recently, filgrastim or lenograstim in combination with plerixafor. Upon initiation of the
mobilisation regimen, patients can expect to undergo their first apheresis session in as little as 4 to 5 days
or, in some cases, 2 to 3 weeks later.1,16,83 The extent of mobilisation is ascertained through evaluation of a
patient’s WBC count. Serial measurements of the patient’s WBC count will assist the clinician in determining the
appropriate time to commence collection procedures. Additionally, centres may use peripheral blood CD34+
cell levels as a surrogate for mobilisation status. Established thresholds for apheresis initiation may vary across
centres, but typically range from 5 to 20 CD34+ cells/microlitre. Although useful in estimating mobilisation
efficacy, peripheral blood CD34+ counts can be variable within and across centres.35,84,85
Once mobilisation has reached an optimal level,
a patient can be scheduled for sessions in the
apheresis centre. An apheresis technician highly
trained in stem cell collections is responsible
for the equipment utilised in the collection
process (Figure 9). Clinical nurses working in the
apheresis unit are responsible for educating the
patient about the stem cell collection process and
monitoring patients for any adverse reactions.
Patients are connected to the apheresis machine
by their catheter. One lumen is used to draw blood
out of the patient and into the machine. Here the
blood is spun at high speeds in a centrifugation
chamber housed within the cell separator
machine. The desired stem cells are collected
during the entire procedure, either in cycles or
continuously, and the remaining blood components
are returned to the patient through the second
lumen of their catheter. This second lumen
additionally can be used to administer intravenous
fluids, electrolyte supplements, and medications
to the patient. Each apheresis session lasts
approximately 2-5 hours during which upwards
to 30 litres of blood, or 6 times the average total human blood volume, is processed. Collections can occur on a
daily basis until the target CD34+ levels are achieved. The apheresis process can last for up to 4 days depending
on patient characteristics and the mobilisation regimen utilised.2,16,17,82,86-88
Figure 9. Example of an Apheresis Machine
Apheresis procedures are relatively safe. Although the mortality rate is quite low at an estimated 3 deaths
per 10,000 procedures,89 apheresis is associated with some morbidity. Citrate is an anticoagulant used during
the apheresis process to prevent blood clotting. Thus, one of the most common adverse effects seen during
this procedure is citrate toxicity manifested as hypocalcaemia. This occurs due to binding of ionised serum
calcium, which leads to hypocalcaemia. Signs and symptoms of citrate toxicity as well as its management are
further described in Table 7. Monitoring serum calcium level prior to and throughout apheresis may decrease
the likelihood of hypocalcaemia.16,82,90 Additional adverse effects of citrate toxicity include hypomagnesaemia,
hypokalaemia, and metabolic alkalosis. Magnesium, like calcium, is a divalent ion that is bound by citrate.
Declines in serum magnesium levels often are more pronounced and take longer to normalise compared to
aberrations in calcium levels. Signs and symptoms of hypomagnesaemia, hypokalaemia, and metabolic alkalosis
as well as their management are further described in Table 7.16,82,90
14
Haematopoietic Stem Cell Mobilisation and Apheresis:
A Practical Guide for Nurses and Other Allied Health Care Professionals
Table 7. Common Apheresis Complications16,82,90
Adverse Effect
Cause
Signs and Symptoms
Corrective Action
Citrate toxicity
Anticoagulant (citrate)
given during apheresis
Hypocalcaemia
Common: dizziness, tingling in area
around the mouth, hands, and feet
Slow the rate of apheresis;
increase the blood:citrate ratio;
calcium replacement therapy
Uncommon: chills, tremors, muscle
twitching and cramps, abdominal
cramps, tetany, seizure, cardiac
arrhythmia
Hypomagnesaemia
Common: muscle spasm or weakness
Uncommon: decrease in vascular tone;
cardiac arrhythmia
Hypokalaemia
Common: weakness
Uncommon: hypotonia and cardiac
arrhythmia
Metabolic alkalosis
Common: worsening of hypocalcaemia
Uncommon: decrease in respiration
rate
Low platelet count, bruising, bleeding
Slow the rate of apheresis;
increase the blood:citrate
ratio; magnesium replacement
therapy
Slow the rate of apheresis;
increase the blood:citrate ratio;
potassium replacement therapy
Slow the rate of apheresis;
increase the blood:citrate ratio
Thrombocytopenia
Platelets adhere to
internal surface of the
apheresis machine
Hypovolaemia
Patient intolerant of
large shift in extracorporeal blood and plasma
volumes
Dizziness, fatigue, light-headedness,
tachycardia, hypotension, diaphoresis,
cardiac arrhythmia
Slow the rate of apheresis
session or temporarily stop it;
intravenous fluid boluses
Catheter
malfunction
Blood clot forms or
catheter is not well
positioned to allow for
adequate blood flow
Inability to flush catheter, fluid collection under skin around catheter site;
pain and erythema at catheter site; arm
swelling, decrease in blood flow
Reposition the catheter; gently
flush catheter; treat blood clot
Infection
Microbial pathogens
enter bloodstream
through catheter or
catheter site
Fever, chills, fatigue, red and
erythematous skin around catheter;
hypotension, positive blood cultures
Administer antibiotics; possibly
remove catheter
Prime apheresis machine with
blood products in place of normal saline; platelet transfusion
Due to large fluctuations in blood volume during apheresis, patients may experience hypovolaemia. Signs
and symptoms of hypovolaemia as well as its management are further described in Table 7.16,82,90 Prior to
starting apheresis, baseline pulse and blood pressure are measured and continuously assessed at regular
intervals. Additionally, it is recommended that haemoglobin and haematocrit also be monitored. Patients at
risk of developing hypovolaemia include those with anaemia, those with a previous history of cardiovascular
compromise, and children or adults with a small frame. Preventative measures are aimed at minimising the
extracorporeal volume shift by priming the apheresis machine with red blood cells and fresh frozen plasma in
place of normal saline. Hypovolaemia may also be managed by providing intravenous fluid boluses and slowing
the rate of flow on the apheresis machine. Another potential problem stemming from hypovolaemia is the
development of a life-threatening cardiac dysrhythmia. If this occurs, apheresis should be interrupted and
symptoms should subside before proceeding with collections.16,82,90
Thrombocytopenia, infection, and catheter malfunction are other complications that may be encountered during
stem cell collections. When the patient’s blood is in the cell separator machine, platelets can adhere to the
centrifuge device. Decreases in platelet concentrations can be precipitous and obtaining platelet counts prior
to each collection is essential. If thrombocytopenia is present pre-apheresis, patients may receive platelet
Chapter 3: Stem Cell Collection (Apheresis), Storage, and Reinfusion
15
transfusions. Additional management of thrombocytopenia during apheresis is the return of platelet-rich
plasma collected during apheresis to the patient at the conclusion of the apheresis session.2,16,82,90 As with any
catheter, frequent manipulation in the absence of proper catheter care and maintenance may predispose the
patient to infections and/or cause the catheter to malfunction. Proper sterile technique should be utilised at all
times to decrease the risk of contamination with microbial pathogens that can lead to bloodstream infections.
Furthermore, routine catheter care should include administration of flushes to prevent blood clot formation.
Commonly observed complications during apheresis are summarised in Table 7.1,2,16,82,83,90
At the conclusion of apheresis, stem cells are isolated from red blood cells and WBCs and then placed in infusion
bags in preparation for cryopreservation and storage. Many centres have cryopreservation laboratories that
maintain collected stem cell products in liquid nitrogen until the time of the patient’s transplantation. A common
cryopreservative used is dimethylsulfoxide (DMSO). DMSO maintains cell viability by preventing ice crystal
formation within the cells during storage.2,82,91 Additionally, the collected product may be manipulated by a
pharmacological, immunological, or physical method to reduce contamination with tumour cells. Quality testing is
performed on collections to ascertain contamination with microbes as well as to determine the number of viable
cells available for transplantation. Once a patient reaches their CD34+ collection goal, apheresis sessions are
complete. Reaching minimum thresholds for CD34+ cell amounts is important as cell dose appears to positively
correlate with engraftment and outcome.17,22,25,32-36,92
The next stage of the AHSCT process is preparing the patient for the actual transplant. Nurses play an
important role in educating patients and caregivers about the transplant processes and procedures as well
as the critical time leading up to engraftment and recovery. Whereas some patients can expect to proceed to
transplant within days following mobilisation, others may undergo the transplantation procedure within a few
weeks following stem cell collection. During the interim, additional chemotherapy may be given to the patient
to help maintain their disease status. Once the transplant date is scheduled, approximately 1 week prior to the
transplant date, patients begin their preparative regimen in the ambulatory or inpatient unit of the hospital. The
preparative regimens may consist of chemotherapy alone or chemotherapy in combination with radiation therapy.
Chemotherapy agents selected for use during this time can be different than those used during previous cancer
treatments and during mobilisation. Often, if similar agents are chosen, the doses during this phase are higher
than previously administered. The patient often benefits from cytoreduction in their tumour following this
phase of treatment. As a consequence of the intensity of treatment, patients experience ablation of their marrow
stores, hence the need for infusion of their previously collected cells as “rescue” therapy.1,2,16,82 Other expected
sequelae from high-dose chemotherapy used in conjunction with AHSCT are summarised in Table 8.1,2,16,82
Table 8. Effects Following High-Dose Chemotherapy Used in AHSCT1,2,16,82
Organ
Effects
Interventions
Gastrointestinal tract
Nausea, vomiting, diarrhoea, anorexia,
mucositis
Antiemetics, mouth care regimens, pain
medications, nutritional supplementation
Blood components
Pancytopenia
Antibiotics, blood transfusions
Kidneys
Haemorrhagic cystitis
Mesna, intravenous fluids, pain medications,
bladder irrigation
Liver
Sinusoidal obstructive syndrome
(veno-occlusive disease)
Diuretics, fluid restriction, intensive supportive care
Brain and nervous system
Headache, tremors, seizures
Pain medications, intensive supportive care
Heart
Oedema, hypertension
Lungs
Atelectasis
Fluid restriction, diuretics, antihypertensive
medications
Pulmonary toilet
Skin
Rash, discoloration
Topical emollients, skin care and bathing regimen
AHSCT, autologous haematopoietic stem cell transplantation.
16
Haematopoietic Stem Cell Mobilisation and Apheresis:
A Practical Guide for Nurses and Other Allied Health Care Professionals
Before high-dose chemotherapy is administered
Figure 10. Storage of Collected Stem Cells
to the patient, the integrity of stored stem cells
is verified. On the day of stem cell infusion, the
previously collected product is removed from liquid
nitrogen storage (Figure 10), thawed, and prepared
for patient administration.17 The infusion itself can
occur in an ambulatory or hospital setting. Prior
to infusion, the product is rigorously inspected
and tested for quality control measures such as
CD34+ cell counts and the presence of microbes.
Several members of the health care team will also
ensure that the product is the patient’s collected
cells. The patient is prepared for the infusion by
receiving premedications (eg, an antihistamine, an
antipyretic), having their intravenous line equipped
to receive the cells, and being placed on medical
equipment to monitor their vital signs throughout
the procedure. The actual time for infusion can
vary based on the patient and the number of bags collected during apheresis, but typically ranges from 30 to
120 minutes. Patients should be frequently monitored for adverse events during the infusion that may require
adjustment of the infusion rate for the product. Resuscitative equipment should be readily available should a
medical emergency occur.1,2,16,82 Frequently encountered reactions during autologous stem cell infusions are
listed in Table 9.1,2,16,82
Table 9. Complications Associated With Autologous Stem Cell Infusion1,2,16,82
Adverse Effect
Reactions to DMSO
Signs and Symptoms
Common: nausea, vomiting, abdominal cramping, headache,
garlic aftertaste
Corrective Action
Treatment of symptoms
Oedema
Rare: Hypotension, rapid heart rate, shortness of breath,
fever, neurologic complications
Fluid retention, puffiness, weight gain, hypertension
Diuretics, fluid restriction
Contamination of
stem cell product
Hypotension, rapid heart rate, shortness of breath, fever,
chills, rigors, positive blood culture for microbial pathogen
Antibiotics, intensive supportive
care
DMSO, dimethylsulfoxide.
The last component of AHSCT is engraftment and recovery. During this critical time, the infused stem cells find
their way back to the bone marrow microenvironment and repopulate depleted marrow stores. Post-transplant,
cytokines are administered to enhance stem cell maturation and to re-establish blood cell components. The
first sign of engraftment is the return of circulating WBCs to a sufficient level defined as an absolute neutrophil
count (ANC) of > 500/mm3 for 3 consecutive days, which typically occurs 7-14 days after the stem cells have
been infused into the patient.1,2 Increased platelet levels (absent of transfusion support) is another indicator
of recovery, and occurs at a later time point, averaging 2-3 weeks following the transplant.1,2 Until engraftment
occurs, patients are at an increased risk of infections, so precautions must be taken to avoid exposure to
microbial pathogens. Patients often require supportive care strategies and therapies, including administration of
antiemetics, pain medications, antibiotics, and nutrition support to ameliorate consequences following the highdose chemotherapy preparative regimen and the subsequent prolonged period of pancytopenia.1,2,16,82
Chapter 3: Stem Cell Collection (Apheresis), Storage, and Reinfusion
17
Chapter 4: How to Discuss Noted Topics With Patients
1
4
Stage Heading
Some of the most important nursing
contributions throughout the AHSCT process
are patient education and psychosocial
support to patients and their families.
Opportunities for teaching are many, from
describing research protocols to explaining
medical procedures and therapies; nurses
in a variety of positions have the expertise
to guide patients throughout the process.
Education about AHSCT should begin prior
to the initial referral for transplantation and
continue throughout the indicated followup period after transplantation. Imparting
knowledge to patients and caregivers not
only eases fears and concerns (Table 10),
but it makes individuals feel empowered in
making the best decisions for themselves
or their loved ones. The education given
This is where a description would go as needed
to patients can occur through a variety of
methods, including explanations and demonstrations, and it is frequently repeated to ensure understanding.
Media to assist patient and caregiver comprehension includes written materials, videos, and group teaching
exercises. Table 11 lists key teaching points nurses often provide patients and their caregivers during the AHSCT
process.1,2,16,82,93
Stage Heading
M
U
Table 10. Sources for Concern
IPS L Experienced by Patients and Caregivers During AHSCT
Chapter 4: Patient Topics
L
M
RE
CE ION
O
L
M
• Ability of the patient toEtolerate
T the procedures surrounding AHSCT
ST LLEC
• Ability of the patient toCOcollect sufficient stem cells to proceed with transplant
• Likelihood of disease relapse after AHSCT
• Response to additional treatment in the setting of disease relapse or poor mobilisation
• Life expectancy of the patient
• Maintaining regularly scheduled appointments for clinic visits and diagnostic procedures
• Secondary complications as a result of AHSCT and their treatment
• Required lifestyle changes and their impacts
• Ability to pay for procedures, treatments, and ancillary expenses (eg, temporary housing, transportation between
home and treating facility, child care)
• Ability to maintain employment during treatment and/or resume employment after therapy
• Ability to maintain social, physical, and/or emotional relationships with others
• is
Psychological
of oneself and loved
ones go as needed
This
wherewell-being
a description
would
AHSCT, autologous haematopoietic stem cell transplantation.
Chapter 4: How to Discuss Noted Topics With Patients
19
Table 11. Key Teaching Points for Nurses Involved in Caring for AHSCT Patients1,2,16,82,93
Stage of AHSCT
Educational Opportunities
Prior and up to the
time of referral for
transplantation
• General overview of the entire transplantation procedure
• Caregiver roles and responsibilities during the procedure
Pre-transplantation
evaluation
• Introduction to members of the transplant team and explanation of each of their roles
in patient care
• Overview of the transplant clinic, including hours of operation
• Explanation of all laboratory tests, scans, and procedures needed for work-up
• Detailed explanation of transplant procedure, including common complications
• Resources available to patients and caregivers to assist with psychosocial support and
coping mechanisms
• Catheter placement and care during transplantation and apheresis
Mobilisation and
apheresis
•
•
•
•
•
•
•
•
•
•
Preparative regimen
• Treatment plan and schedule of conditioning chemotherapy, including expected adverse
effects and how to manage them
• Review of supportive care medications that may be used during this time
• Preventative measures for development of infections
Stem cell infusion
• Process for thawing and infusing stem cells
• Potential complications following infusion of cells and how these effects are managed
• How patient will be monitored during the infusion and thereafter
Engraftment and recovery
•
•
•
•
•
•
•
Monitoring and follow-up
• Clinic appointment schedule
• How to monitor progress at home and when it is necessary to contact a health care
professional
• Long-term sequelae following transplantation and secondary complications
• Risk and management of relapsed disease
How and when to administer agents used in the mobilisation process
Schedule of chemotherapy used in the mobilisation process
What medications a patient should and should not take during mobilisation
Expected adverse effects and their management for all agents used in mobilisation
Review of care of catheter used for apheresis
Explanation of apheresis procedure
Expected adverse effects from apheresis procedure
Importance of laboratory monitoring and how to manage electrolyte imbalances
Stem cell collection target level
Options for patients who mobilise poorly or fail to mobilise
Monitoring parameters and laboratory testing used to assess patient status
Reinforcement of neutropenic precautions
Signs and symptoms of infection and treatments available to manage patients
Significance of blood counts and how engraftment and recovery are determined
Other expected complications following transplantation and their management
Discharge planning process
Discharge medication education with respect to how to take medications at home and
expected adverse effects
• Any necessary lifestyle changes
AHSCT, autologous haematopoietic stem cell transplantation.
20
Haematopoietic Stem Cell Mobilisation and Apheresis:
A Practical Guide for Nurses and Other Allied Health Care Professionals
Initial teaching about AHSCT ideally begins at the time of the initial diagnosis of cancer or other disease.
Although some patients may not proceed to AHSCT, possession of basic knowledge of state-of-the-art treatment
throughout their continuum of care will empower the patient to make difficult decisions. The nurses in the
medical haematology/oncology clinic or unit should assist patients in understanding what role, if any, an AHSCT
has in their care. This is the time to introduce basic concepts of the mobilisation procedures, the stem cell
transplant, and the period following transplantation.
Once a patient is evaluated in a transplant centre, they will meet nurses who have different roles within
the transplant programme. For example, a nurse coordinator is responsible for directing the pre-transplant
preparation through the coordination of medical testing and evaluation. The nurse coordinator collaborates
with clinic nurses to educate patients and their families, giving them an overview of the clinic operations and
detailed explanations of the procedures surrounding the transplantation process. After a patient is approved
for the transplantation, nurses in the clinic will assist with coordinating care with the apheresis centre,
including scheduling appropriate catheter placement and providing any associated teaching. The nurses also
assist with any psychosocial needs and make referrals to other members of the team as necessary (eg, social
workers). Nurses should also encourage patients and their caregivers to achieve their own educational goals by
encouraging them to ask the medical team any questions they may have prior to initiating any procedures.
During mobilisation and apheresis, nurses will remain in close contact with patients and their families,
communicating information regarding follow-up for apheresis procedures, total CD34+ counts post-apheresis,
and the next phase of the plan of care. Prior to starting apheresis, adverse effects of this procedure are
explained as well as the management of their central venous catheters. It is important for nurses to recognise
patients at greatest risk of poor mobilisation. In such instances, nurses should possess basic knowledge about
remobilisation strategies and how to proceed with treatment and, moreover, whether AHSCT will be a treatment
option. If the nurse can confidently discuss potential options, the patient and their family members may have
greater confidence that the nurse is their advocate, thus reducing any additional fears and stressors.
The provision of care surrounding the actual stem cell transplant, including administration of the preparative
regimen, the stem cell infusion, and supporting the patient through engraftment and recovery create
opportunities for nurses to provide patients some of the most intensive and extensive education during the
multiple processes involved in AHSCT. Numerous medications are utilised during this time period, most of
which have the potential for serious adverse effects and/or drug interactions. It is not unusual for patients
to experience times of extreme debilitation and emotional exhaustion. Nurses can expect to assist with the
management of adverse effects through supportive care mechanisms and be attentive to the concerns and
anxiety expressed by patients and caregivers. Following recovery from transplantation, nurses continue to
support patients through the discharge process, preparing them for the transition of care into the home setting.
Even after the patient has recovered from the transplant, the educational role of the nurse continues. Patients
continue to need counselling and guidance about lifestyle changes and when resumption of pre-transplant
activities can be expected. An understanding of routine follow-up visits and medical surveillance are essential for
positive patient outcomes. Long-term sequelae from chemotherapy and other treatment modalities should be a
part of the educational process during the post-transplant period. It is also prudent to discuss the possibility of
disease relapse with patients and how management of their disease will be handled should this occur. Overall,
nursing education administered to the transplant recipient is a complex and dynamic process that should be
personalised to the patient’s disease, treatment plan, cognitive level, and psychosocial needs.
Chapter 4: How to Discuss Noted Topics With Patients
21
Glossary
Allogeneic: refers to 2 different persons who do not share the same genetic composition
Adaptive immunity: function of the immune system that is highly specific and is acquired through exposure to
specific antigens
Apheresis: the process of removing blood from an individual, separating cellular components, and then
returning remaining portions back to the donor
Autologous: refers to when one is both the donor and the recipient
Autologous haematopoietic stem cell transplantation: medical procedure involving the collection and
storage of a person’s blood stem cells followed by administration of high dose chemotherapy and/or radiation
therapy with subsequent reinfusion of stem cells to restore normal blood cell production
Chemokines: a subset of cytokines that serve as chemoattractants responsible for guiding the migration of
cells
Chemomobilisation: the process of mobilising stem cells from the bone marrow into the peripheral blood
through the use of chemotherapy in conjunction with one or more cytokines such as filgrastim
Cryopreservation: the process of storing cells, tissues, or organs by a cooling mechanism that maintains the
viability of the product for later use
Cryopreservative: also known as cryoprotectant; a substance added to collected cells prior to storage to
prevent dehydration or the formation of ice crystals that can decrease the viability of the product upon thawing.
An example is dimethylsulfoxide (DMSO)
Cytokines: small proteins released by cells that facilitate cellular behaviour as well as communication and
interaction between cells
Cytoreduction: the reduction in the number of cancer cells
Engraftment: when infused stem cells begin to proliferate and make new blood cellular components. Often this
is defined in relation to minimum levels for neutrophil and platelet counts
Haematopoiesis: the process of producing new blood cell components
Haemostasis: regulation of the blood system to maintain stable, constant conditions relating to bleeding and
clotting
Innate immunity: function of the immune system that is nonspecific, naturally present, and does not rely on
prior exposure to an antigen
Mobilisation: the process of increasing the number of stem cells from the bone marrow into the peripheral
circulation prior to collection
Monoclonal antibody: a type of antibody produced from a single clone of immune cells
Myelosuppression: the inhibition of bone marrow activity often resulting in decreased production of blood
components
Pancytopenia: a decrease in all types of blood cells, including white blood cells, red blood cells, and platelets
Pluripotent: describes cells that have the ability to self-replicate and the potential to differentiate into specific
cell types
Progenitor: a precursor or original cell that may or may not be capable of self-renewal
Remobilisation: the process of mobilisation after failure from a previous attempt
Stromal: refers to the stroma; the stroma is the supportive framework of tissue that usually comprises
connective tissue
Syngeneic: refers to 2 different persons with the exact genetic composition (ie, identical twins)
Tandem autologous stem cell transplantation: process in which a person receives 2 scheduled,
sequential transplants with their own stem cells collected prior to the first transplant
Glossary
23
Glossary, References,
and Additional Resources
Rituximab: a chimeric monoclonal antibody that binds to CD20 protein on the surface of cells
References
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Haematopoietic Stem Cell Mobilisation and Apheresis:
A Practical Guide for Nurses and Other Allied Health Care Professionals
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35. Pusic I, Jiang SY, Landua S, et al. Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for
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41. Bishop MR, Anderson JR, Jackson JD, et al. High-dose therapy and peripheral blood progenitor cell transplantation: effects of
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42. Kopf B, De Giorgi U, Vertogen B, et al. A randomized study comparing filgrastim versus lenograstim versus molgramostim plus
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43. Petit I, Szyper-Kravitz M, Nagler A, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and upregulating CXCR4. Nat Immunol. 2002;3(7):687-694.
44. Levesque JP, Hendy J, Takamatsu Y, Williams B, Winkler IG, Simmons PJ. Mobilization by either cyclophosphamide or granulocyte
colony-stimulating factor transforms the bone marrow into a highly proteolytic environment. Exp Hematol. 2002;30(5):440-449.
45. Heissig B, Hattori K, Dias S, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9
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46. Levesque JP, Takamatsu Y, Nilsson SK, Haylock DN, Simmons PJ. Vascular cell adhesion molecule-1 (CD106) is cleaved by
neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating
factor. Blood. 2001;98(5):1289-1297.
47. Neupogen® (filgrastim) [summary of product characteristics]. Cambridge, United Kingdom: Amgen Ltd; 2009. Please refer to the
applicable national summary of product characteristics.
48. Granocyte® (lenograstim) [summary of product characteristics]. London, United Kingdom: Chugai Pharma UK Ltd; 2009. Please
refer to the applicable national summary of product characteristics.
49. Kroger N, Renges H, Kruger W, et al. A randomized comparison of once versus twice daily recombinant human granulocyte
colony-stimulating factor (filgrastim) for stem cell mobilization in healthy donors for allogeneic transplantation. Br J Haematol.
2000;111(3):761-765.
50. Kim S, Kim HJ, Park JS, et al. Prospective randomized comparative observation of single- vs split-dose lenograstim to mobilize
peripheral blood progenitor cells following chemotherapy in patients with multiple myeloma or non-Hodgkin’s lymphoma. Ann
Hematol. 2005;84(11):742-747.
51. Komeno Y, Kanda Y, Hamaki T, et al. A randomized controlled trial to compare once- versus twice-daily filgrastim for mobilization
of peripheral blood stem cells from healthy donors. Biol Blood Marrow Transplant. 2006;12(4):408-413.
52. Flinn IW, O’Donnell PV, Goodrich A, et al. Immunotherapy with rituximab during peripheral blood stem cell transplantation for
non-Hodgkin’s lymphoma. Biol Blood Marrow Transplant. 2000;6(6):628-632.
53. Naparstek E. The role of the anti-CD20 antibody rituximab in hematopoietic stem cell transplantation for non-Hodgkin’s
lymphoma. Curr Hematol Rep. 2005;4(4):276-283.
54. Cytoxan® (cyclophosphamide injection) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; 2005.
55. Etoposide injection [prescribing information]. Bedford, OH: Bedford Laboratories; 2008.
56. Mozobil® (plerixafor) [summary of product characteristics]. Naarden, The Netherlands: Genzyme Europe B.V.; 2009. Please refer
to the applicable national summary of product characteristics.
57. Martin C, Bridger GJ, Rankin SM. Structural analogues of AMD3100 mobilise haematopoietic progenitor cells from bone marrow
in vivo according to their ability to inhibit CXCL12 binding to CXCR4 in vitro. Br J Haematol. 2006;134(3):326-329.
58. Hatse S, Princen K, Bridger G, De Clercq E, Schols D. Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4.
FEBS Lett. 2002;527(1-3):255-262.
59. Fricker SP, Anastassov V, Cox J, et al. Characterization of the molecular pharmacology of AMD3100: a specific antagonist of the
G-protein coupled chemokine receptor, CXCR4. Biochem Pharmacol. 2006;72(5):588-596.
60. Gerlach LO, Skerlj RT, Bridger GJ, Schwartz TW. Molecular interactions of cyclam and bicyclam non-peptide antagonists with the
CXCR4 chemokine receptor. J Biol Chem. 2001;276(17):14153-14160.
61. Broxmeyer HE, Orschell CM, Clapp DW, et al. Rapid mobilization of murine and human hematopoietic stem and progenitor cells
with AMD3100, a CXCR4 antagonist. J Exp Med. 2005;201(8):1307-1318.
62. Devine SM, Flomenberg N, Vesole DH, et al. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist
AMD3100 to patients with multiple myeloma and non-Hodgkin’s lymphoma. J Clin Oncol. 2004;22(6):1095-1102.
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Haematopoietic Stem Cell Mobilisation and Apheresis:
A Practical Guide for Nurses and Other Allied Health Care Professionals
Additional Resources
• American Cancer Society: http://www.cancer.org
• American Society for Blood and Marrow Transplantation (ASMBT): http://www.asbmt.org
• American Society for Apheresis (ASFA): http://www.apheresis.org
• Blood and Marrow Transplant Information Network (BMT InfoNet): http://www.bmtinfonet.org
• Cancerworld: http://www.cancerworld.org
• Center for International Blood and Marrow Transplant Research (CIBMTR): http://www.cibmtr.org
• The European Group for Blood & Marrow Transplantation (EBMT): http://www.ebmt.org
• International Myeloma Foundation: http://myeloma.org
• LeukemiaNet: http://www.leukemia-net.org
• Leukemia and Lymphoma Society: http://www.leukemia-lymphoma.org
• Leukemia Research Foundation: http://www.leukemia-research.org
• Lymphomainfo.net: http://www.lymphomainfo.net
• Lymphoma Coalition: http://www.lymphomacoalition.org
• Lymphoma Forum and Lymphoma Association: http://www.lymphoma.org.uk
• Lymphoma Research Foundation: http://www.lymphoma.org
• Myeloma Euronet: http://www.myeloma-euronet.org
• Multiple Myeloma Research Foundation: http://www.multiplemyeloma.org
• National Bone Marrow Transplant Link (NBMT Link): http://www.nbmtlink.org
• National Cancer Institute: http://www.cancer.gov
• National Marrow Donor Program: http://www.marrow.org
Additional Resources
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Haematopoietic Stem Cell Mobilisation and Apheresis:
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Haematopoietic Stem Cell Mobilisation and Apheresis:
A Practical Guide for Nurses and Other Allied Health Care Professionals
This brochure was made possible by a
financial contribution from
Genzyme Europe B.V.