Haematopoietic Stem Cell Mobilisation and Apheresis: - EBMT
Haematopoietic Stem Cell Mobilisation and Apheresis: - EBMT
Haematopoietic Stem Cell Mobilisation and Apheresis: - EBMT
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<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong><br />
<strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for<br />
Nurses <strong>and</strong> Other Allied<br />
Health Care Professionals<br />
I
The European Group for Blood <strong>and</strong> Marrow Transplantation<br />
gratefully acknowledges the following individuals for their<br />
critical review <strong>and</strong> contributions to this guide:<br />
Erik Aerts (RN) Switzerl<strong>and</strong><br />
Aleks<strong>and</strong>ra Babic (RN) Italy<br />
Hollie Devine (RN) USA<br />
Francoise Kerache (RN) Germany<br />
Arno Mank (RN) Netherl<strong>and</strong>s<br />
Harry Schouten (MD) Netherl<strong>and</strong>s<br />
Nina Worel (MD) Austria
<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong><br />
<strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other<br />
Allied Health Care Professionals<br />
Table of Contents<br />
Chapter 1: Overview of Autologous <strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> Transplantation. . . . . . . . . . . . . . 1<br />
Chapter 2: <strong>Mobilisation</strong>. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5<br />
Chapter 3: <strong>Stem</strong> <strong>Cell</strong> Collection (<strong>Apheresis</strong>), Storage, <strong>and</strong> Reinfusion.. . . . . . . . . . . . . . . . . . . . 13<br />
Chapter 4: How to Discuss Noted Topics With Patients.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19<br />
Glossary .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23<br />
References.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24<br />
Additional Resources .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27<br />
Notes.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28<br />
Table of Contents
Chapter 1:<br />
Overview of Autologous <strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> Transplantation<br />
Widely accepted cancer treatment strategies include chemotherapy <strong>and</strong> radiotherapy. The rationale for<br />
administration of high-dose chemotherapy <strong>and</strong>/or radiation to patients with therapy-sensitive tumours is to<br />
reduce tumour burden. Delivery of these therapies with respect to higher drug doses <strong>and</strong> intensified schedule<br />
are often limited by organ toxicities (eg, bone marrow, heart, <strong>and</strong> lung) <strong>and</strong> pancytopenia. To overcome<br />
these dose limitations, autologous haematopoietic stem cell transplantation (AHSCT), high-dose<br />
therapy supported by the infusion of haematopoietic stem cells, has evolved as a medical procedure to allow for<br />
administration of intense drug doses with tolerable organ <strong>and</strong> haematopoietic toxicity. Infusion of autologous<br />
stem cells following dose-intensive treatment “rescues” the bone marrow by re-establishing normal<br />
haematopoiesis. Upon regeneration of bone marrow function, patients may be cured from their disease or<br />
receive additional cancer treatment. 1,2<br />
Chapter 1: Overview<br />
Autologous haematopoietic stem cell transplantation is a complex medical procedure that has been used to<br />
treat <strong>and</strong> cure patients with various malignant <strong>and</strong> non-malignant disorders. Although the first documentation of<br />
AHSCT use to treat cancer was reported in the 1890s, 3 achievement of a cure in patients with a malignancy was<br />
only documented in 1978 following a clinical trial conducted at the National Cancer Institute (United States). 4<br />
Subsequent to this report, numerous advances have been made in the art of AHSCT <strong>and</strong> thous<strong>and</strong>s of patients<br />
around the world have had their diseases successfully managed through the use of AHSCT.<br />
The term “autologous haematopoietic stem cell transplantation” is frequently used interchangeably with the<br />
terms autologous bone marrow transplantation (aBMT), autologous peripheral blood stem cell transplantation<br />
(aPBSCT), <strong>and</strong> autologous haematopoietic cell transplantation (AHCT). 5 “Autologous” means that the donor cells<br />
used for the procedure are from the patient himself, as opposed to “allogeneic,” which refers to a cell donor<br />
other than the patient. In certain allogeneic circumstances, the term “syngeneic” is used when the cell donor<br />
is a patient’s identical twin. The source of stem cells for collection is identified by the terms “bone marrow” <strong>and</strong><br />
“peripheral blood.” <strong>Cell</strong>s for the patient may be collected either from the donor’s bone marrow reserves, such<br />
as those stored in the iliac crest of the pelvic bones, or from the donor’s peripheral blood. Additionally, umbilical<br />
cord blood (UCB), found in the umbilical cord <strong>and</strong> placenta following childbirth, is another source of progenitor<br />
stem cells used in clinical practice in the setting of allogeneic transplants. 6 When 2 autologous stem cell<br />
transplantations occur in a scheduled, sequential fashion, this process is referred to as “t<strong>and</strong>em autologous<br />
stem cell transplantation.” 6,7<br />
In the more than 3 decades following the first successful use of AHSCT, the utility of this treatment for malignant<br />
<strong>and</strong> non-malignant conditions has been well established (Table 1). 8 In the setting of relapsed malignant<br />
conditions, st<strong>and</strong>ard chemotherapy regimens may produce unacceptable rates of bone marrow suppression<br />
(myelosuppression), resulting in a low white cell count, low platelet count, <strong>and</strong> anaemia. This increases the<br />
risk of potentially fatal infections <strong>and</strong> bleeds. Following chemotherapy, the patient is therefore given a transplant<br />
of stem cells to regenerate damaged bone marrow. Thus, the reinfusion of autologous stem cells has become a<br />
therapeutic modality for reducing prolonged myelosuppression. 9-11 Data demonstrate that high-dose therapy with<br />
stem cell rescue has a positive impact on disease response rates; however, for some patients it fails to improve<br />
overall survival when compared to conventional chemotherapy treatments. Thus, the definitive role of AHSCT in<br />
certain situations, such as the treatment of refractory or relapsed Hodgkin’s lymphoma or chronic lymphocytic<br />
leukaemia, remains inconclusive 12-15 <strong>and</strong> indications for AHSCT continue to evolve.<br />
Chapter 1: Overview of Autologous <strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> Transplantation<br />
1
Table 1. Indications for Autologous <strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> Transplantation in Adults 8<br />
Disease<br />
Acute lymphoid<br />
leukaemia<br />
Acute myeloid<br />
leukaemia<br />
Chronic lymphoid<br />
leukaemia<br />
Chronic myeloid leukaemia<br />
Myelofibrosis<br />
Myelodysplastic<br />
syndrome<br />
Diffuse large<br />
B-cell NHL<br />
Mantle cell<br />
lymphoma<br />
Lymphoblastic<br />
lymphoma <strong>and</strong><br />
Burkitt’s lymphoma<br />
Follicular B-cell NHL<br />
St<strong>and</strong>ard of Care<br />
CR1 (intermediate risk)<br />
M3 (molecular CR2)<br />
Chemosensitive relapse;<br />
≥ CR2<br />
CR1<br />
Chemosensitive relapse;<br />
≥ CR2<br />
Chemosensitive relapse;<br />
≥ CR2<br />
Optional Based on<br />
Risks <strong>and</strong> Benefits<br />
CR1 (low or high risk)<br />
CR2<br />
Poor risk disease<br />
RAEBt<br />
sAML in CR1 or CR2<br />
CR1 (intermediate or high<br />
IPI at diagnosis)<br />
CR1<br />
Chemosensitive relapse;<br />
≥ CR2<br />
CR1 (intermediate or high<br />
IPI at diagnosis)<br />
Investigational or<br />
Additional Trials<br />
Needed<br />
CR1 (st<strong>and</strong>ard,<br />
intermediate or high risk)<br />
First (CP), failing imatinib<br />
Accelerated phase or ><br />
first CP<br />
Generally Not<br />
Recommended<br />
CR2 (incipient relapse)<br />
Relapsed or refractory disease<br />
CR3 (incipient relapse)<br />
M3 (molecular persistence)<br />
Relapsed or refractory disease<br />
Blast crisis<br />
Primary or secondary with an<br />
intermediate or high Lille score<br />
RA<br />
RAEB<br />
More advanced stages<br />
Refractory disease<br />
Refractory disease<br />
Refractory disease<br />
Refractory disease<br />
T-cell NHL CR1 Chemosensitive relapse;<br />
Refractory disease<br />
≥ CR2<br />
Hodgkin’s lymphoma Chemosensitive relapse; Refractory disease<br />
CR1<br />
≥ CR2<br />
Lymphocyte predominant<br />
Chemosensitive relapse;<br />
CR1<br />
nodular Hodgkin’s<br />
lymphoma<br />
≥ CR2<br />
Refractory disease<br />
Multiple myeloma<br />
<br />
Amyloidosis<br />
<br />
Severe aplastic anaemia<br />
<br />
Paroxysmal nocturnal<br />
<br />
haemoglobinuria<br />
Breast cancer*<br />
Adjuvant high risk disease<br />
Metastatic responding<br />
Metastatic<br />
responding<br />
Germ cell tumours Third-line refractory Sensitive relapses<br />
Ovarian cancer CR/PR Platinum-sensitive relapse<br />
Medulloblastoma* Post-surgery Post-surgery<br />
Small cell lung cancer<br />
Limited disease<br />
Renal cell carcinoma<br />
Metastatic, cytokine-refractory<br />
Soft cell sarcoma<br />
Metastatic, responding<br />
Immune cytopenias<br />
<br />
Systemic sclerosis<br />
<br />
Rheumatoid arthritis<br />
<br />
Multiple sclerosis<br />
<br />
Systemic lupus<br />
<br />
erythematosus<br />
Crohn’s disease<br />
<br />
Chronic inflammatory<br />
<br />
demyelinating<br />
polyradiculoneuropathy<br />
CP, chronic phase; CR1, 2, 3, first, second, or third complete remission; CR/PR, complete response/partial response; IPI, International<br />
Prognostic Index; NHL, non-Hodgkin’s lymphoma; RA, refractory anaemia; RAEB, refractory anaemia with excess blasts; RAEBt,<br />
refractory anaemia with excess blasts in transformation; sAML, secondary acute myelogenous leukaemia; indicates use of autologous<br />
haematopoietic stem cell transplantation regardless of stage.<br />
* For patients with metastatic responding breast cancer or medulloblastoma, autologous haematopoietic stem cell transplantation can be<br />
considered when the benefits outweigh the risks, although additional studies are warranted.<br />
2<br />
<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> <strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other Allied Health Care Professionals
An AHSCT is a complex process involving a multidisciplinary approach <strong>and</strong> resource utilisation. Historically,<br />
this treatment was offered only at large academic medical centres. However, due to medical progress <strong>and</strong> our<br />
knowledge of the AHSCT procedure, patients are receiving this therapy in community settings. The stem cell<br />
transplant process can be summarised in 8 distinct phases (Figure 1): (1) administration of mobilisation<br />
agents, (2) mobilisation, (3) collection, (4) preparation of product for storage, (5) cryopreservation, (6)<br />
administration of preparative regimen, (7) stem cell transplantation, <strong>and</strong> 8) engraftment <strong>and</strong> recovery. 1,2,6,16<br />
For a more detailed explanation of each phase, please see Chapter 3.<br />
Figure 1. The <strong>Stem</strong> <strong>Cell</strong> Transplant Process 1,2,6,16<br />
1<br />
Injections<br />
<strong>Mobilisation</strong><br />
2 3<br />
Collection<br />
Injections of mobilisation agents<br />
<strong>Stem</strong> cells are stimulated to move into the<br />
bloodstream from the bone marrow space<br />
Collection of mobilised stem cells from the blood<br />
using the apheresis machine<br />
4<br />
Preparation for Storage<br />
5<br />
Cryopreservation<br />
6<br />
Chemotherapy<br />
<strong>and</strong>/or Radiation<br />
<strong>Stem</strong> cells collected are stored in infusion bags<br />
Freezing of stem cells for use after completion of<br />
preparative regimen<br />
Administration of preparative regimen intended to<br />
kill any remaining cancer cells <strong>and</strong> make a space for<br />
new cells to live<br />
7<br />
<strong>Stem</strong> <strong>Cell</strong> Transplant<br />
8<br />
Engraftment <strong>and</strong> Recovery<br />
Previously collected stem cells are thawed <strong>and</strong> infused<br />
back into the bloodstream<br />
One aim of autologous stem cell transplant is for infused stem cells to mature into functional blood components such as neutrophils<br />
<strong>and</strong> platelets. The first signs of engraftment <strong>and</strong> recovery include increasing absolute neutrophil <strong>and</strong> platelet counts<br />
Chapter 1: Overview of Autologous <strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> Transplantation<br />
3
Once patients are identified as being c<strong>and</strong>idates for AHSCT, they undergo detailed evaluations to ensure that they<br />
will be able to tolerate the procedure. Patients are administered exogenous agents to stimulate the migration<br />
of progenitor cells from the bone marrow into the peripheral blood. Procurement of these cells is achieved by<br />
apheresis. At the conclusion of apheresis, cells are processed <strong>and</strong> cryopreserved for future use. Product<br />
storage time is typically a few weeks to months, although some investigators have reported storing product<br />
for up to 14 years without loss of product viability. 17-19 Following apheresis, patients may receive additional<br />
chemotherapy to treat their underlying disease or proceed directly to receiving a transplant preparative regimen<br />
(ie, high dose chemotherapy ± radiotherapy) followed by infusion of previously collected stem cells. The first<br />
signs of engraftment, indicated by an increase in white blood cell (WBC) counts, usually occur within 2 to 4<br />
weeks following the infusion of autologous stem cells. 1,2<br />
4<br />
<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> <strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other Allied Health Care Professionals
Chapter 2: <strong>Mobilisation</strong><br />
Haematopoiesis refers to the production of cellular components of blood. This process occurs continually to<br />
maintain normal immune system function <strong>and</strong> haemostasis. In adults, haematopoiesis primarily occurs in the<br />
bone marrow that is contained within the pelvis, sternum, vertebral column, <strong>and</strong> skull. 20,21 Production of mature<br />
blood cells specifically occurs in the bone marrow microenvironment (Figure 2). 20-22<br />
Figure 2. Bone Marrow Microenvironment 20-22<br />
Chapter 2: <strong>Mobilisation</strong><br />
All blood cells are derived from progenitor stem cells, also referred to as pluripotent stem cells. These cells<br />
have the capacity for unlimited self-renewal <strong>and</strong> the ability to differentiate into all types of mature blood cells.<br />
The pluripotent stem cell can differentiate into 1 of 2 types of common progenitor cells—the common myeloid<br />
progenitor <strong>and</strong> the common lymphoid progenitor. These common progenitor cells can further differentiate<br />
into committed cellular components through an intricate cascade of events (Figure 3). The end result is the<br />
production of cells in the myeloid lineage <strong>and</strong> the lymphoid lineage. <strong>Cell</strong>s in the myeloid lineage, such as red<br />
blood cells, platelets, macrophages, <strong>and</strong> neutrophils are responsible for tissue nourishment, oxygenation, blood<br />
viscosity, coagulation, <strong>and</strong> immune function such as innate <strong>and</strong> adaptive immunity. The lymphoid lineage<br />
components, namely T cells <strong>and</strong> B cells, provide the foundation for the adaptive immune system. 2,20<br />
Cytokines play an integral role in haematopoiesis. When progenitor cells are exposed to cytokines, the<br />
maturation cascade to produce committed mature blood cell components can occur. Examples of important<br />
cytokines are listed in Figure 3. These cytokines are found endogenously, although during the stem cell collection<br />
process, some are often exogenously administered to patients in an effort to enhance the yield of stem<br />
cells within a short time period. 21-25 Examples of these exogenous cytokines include filgrastim (glycosylated<br />
granulocyte colony-stimulating factor [G-CSF]) <strong>and</strong> lenograstim (non-glycosylated G-CSF).<br />
Chapter 2: <strong>Mobilisation</strong><br />
5
Figure 3. <strong>Stem</strong> <strong>Cell</strong> Maturation Cascade 2,20<br />
Epo, erythropoietin; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor;<br />
IL, interleukin; M-CSF, macrophage colony-stimulating factor; SCF, stem cell factor; Tpo, thrombopoietin.<br />
Chemokines are a subset of cytokines associated with a single receptor <strong>and</strong> assist in cell movement.<br />
Stromal cells are layers of cells that support the bone marrow microenvironment. These cells produce the<br />
chemokine stem cell derived factor-1 alpha (SDF-1α). This chemokine is an important signalling molecule involved<br />
in the proliferation, homing, <strong>and</strong> engraftment of stem cells. For a given time in their development, stem cells<br />
express the chemokine receptor CXCR4. CXCR4 is responsible for anchoring stem cells to the bone marrow<br />
microenvironment. When CXCR4 <strong>and</strong> SDF-1α bind, interactions between integrins <strong>and</strong> cell adhesion molecules<br />
also occur. The anchoring of stem cells within the bone marrow microenvironment occurs by continuous<br />
production of SDF-1α by stromal cells. It is the loss of attachment to the stromal cells, along with the loss of<br />
SDF-1α activity, that favours the release of stem cells into peripheral circulation. Blockade of this receptor with<br />
a chemokine antagonist (such as plerixafor) has elevated circulating haematopoietic stem cells (HSCs) <strong>and</strong> aided<br />
stem cell collections in patients with multiple myeloma <strong>and</strong> lymphoma. 26-31<br />
6<br />
<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> <strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other Allied Health Care Professionals
Pluripotent stem cells express the cell surface marker antigen CD34. This marker is the indicator most frequently<br />
used in clinical practice to determine the extent <strong>and</strong> efficiency of peripheral blood stem cell collections. 25<br />
Although not a complete measure of the quantity <strong>and</strong> quality of collected cells, blood samples from collections<br />
are assayed to determine the number of CD34+ cells present. Once specific cell targets are achieved, cell<br />
collections are completed <strong>and</strong> stored for future use. St<strong>and</strong>ard target levels can vary among treatment centres<br />
<strong>and</strong> a patient’s specific goal is related to the underlying disease, the source of stem cells, <strong>and</strong> the type of<br />
transplantation to be performed. In general, a target level of 2 × 10 6 CD34+ cells/kg body weight is considered<br />
the minimum for autologous transplantation, with optimal levels being ≥ 5 × 10 6 CD34+ cells/kg for a single<br />
transplant <strong>and</strong> ≥ 6 × 10 6 CD34+ cells/kg for a t<strong>and</strong>em transplant. 23,25,32-36<br />
Historically, autologous stem cell collections involved<br />
the removal of bone marrow cells from a patient’s<br />
bilateral posterior iliac crest region (Figure 4) under<br />
general anaesthesia in a hospital operating room.<br />
However, due to advances in medical technology, most<br />
collections today are performed by apheresis (Figure<br />
5). Peripheral blood stem cell collection is considered<br />
the preferred method for mobilisation prior to AHSCT<br />
due to patient convenience, decreased morbidity, <strong>and</strong><br />
faster engraftment of WBCs <strong>and</strong> platelets. Additional<br />
comparisons between harvest of bone marrow <strong>and</strong><br />
peripheral blood for autologous transplantation are<br />
summarised in Table 2. 1,2,37-40<br />
Figure 4. Bone Marrow Harvest<br />
Table 2. Advantages <strong>and</strong> Disadvantages of <strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> Collection Methods 1,2,37-40<br />
Collection<br />
Method<br />
Advantages<br />
Disadvantages<br />
Bone marrow • Single collection<br />
• No need for special catheter placement<br />
• Use of cytokines not necessary<br />
Peripheral<br />
blood<br />
• Does not require general anaesthesia <strong>and</strong><br />
can be performed in an outpatient setting<br />
• Faster neutrophil <strong>and</strong> platelet<br />
engraftment<br />
• Associated with lower rates of morbidity<br />
<strong>and</strong> mortality<br />
• Potentially less tumour cell contamination<br />
of product<br />
• Performed in an acute care setting since it<br />
requires general anaesthesia<br />
• Slower neutrophil <strong>and</strong> platelet engraftment<br />
• Higher rates of morbidity <strong>and</strong> mortality<br />
• Potentially more tumour cell contamination of<br />
product<br />
• Collection may take several days<br />
• Sometimes requires placement of large-bore,<br />
double-lumen catheter for collection<br />
• Haemorrhage, embolism, <strong>and</strong> infection are<br />
possible complications related to insertion of<br />
central venous catheter<br />
Chapter 2: <strong>Mobilisation</strong><br />
7
Figure 5. <strong>Apheresis</strong> Collection<br />
The concentrations of HSCs are 10-<br />
100 times greater in the bone marrow<br />
compared to the peripheral circulation. 1<br />
Therefore, methods to increase the<br />
circulating concentrations of HSCs<br />
are necessary to ensure adequate<br />
<strong>and</strong> successful collections. Agents<br />
used to mobilise HSCs include the<br />
administration of cytokines with or<br />
without chemotherapy prior to scheduled<br />
collection periods.<br />
Filgrastim <strong>and</strong> lenograstim used as single-agent mobilisers have been well established, with both agents<br />
having reliably demonstrated increased concentrations of circulating HSCs. 41,42 G-CSF is thought to stimulate<br />
HSC mobilisation by decreasing SDF-1α gene expression <strong>and</strong> protein levels while increasing proteases that<br />
can cleave interactions between HSCs <strong>and</strong> the bone marrow environment. 43-46 The mechanism of action for<br />
G-CSF is illustrated in Figure 6. 43-46 The recommended dose of filgrastim <strong>and</strong> lenograstim is 10 mcg/kg/day as<br />
a subcutaneous injection for multiple days. 47,48 However, these growth factors are typically given at a total daily<br />
dosage of 3-24 mcg/kg/day. 25 Data indicate that divided doses of G-SCF (eg, lenograstim 5 mcg/kg twice daily)<br />
are more efficacious than single-dose administration (eg, lenograstim 10 mcg/kg once daily) by producing a<br />
higher yield of CD34+ cells <strong>and</strong> the need for fewer apheresis procedures. 49-51 However, current clinical practice<br />
does not favour one schedule over the other.<br />
Figure 6. Mechanism of Action of G-CSF 43-46<br />
CXCR4, chemokine receptor 4; G-CSF, granulocyte colony-stimulating factor; SDF-1α, stromal cell derived factor-1 alpha.<br />
8<br />
<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> <strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other Allied Health Care Professionals
Since it is common to see an increase in HSCs following recovery from myelosuppressive chemotherapy, another<br />
method to mobilise HSCs involves the administration of chemotherapy, usually in conjunction with cytokines. 22,24,25<br />
This is frequently referred to as “chemomobilisation.” Chemotherapy <strong>and</strong> cytokines work synergistically<br />
to mobilise HSCs, although the exact mechanism for chemotherapy mobilisation has not been fully explained.<br />
Possible mechanisms for mobilisation following chemotherapy include chemotherapy effects on the expression<br />
of cell adhesion molecules in the bone marrow <strong>and</strong> chemotherapy-induced damage to stromal cells in the bone<br />
marrow. Both of these lead to increased circulating concentrations of HSCs due to disruption of the bone marrow<br />
microenvironment. 28 The kinetics of CD34+ cell <strong>and</strong> WBC production following chemotherapy <strong>and</strong> growth factor<br />
administration are illustrated in Figure 7.<br />
Figure 7. Generalised Kinetics of Leucocyte <strong>and</strong> CD34+ <strong>Cell</strong> Chemotherapeutic agents<br />
<strong>Mobilisation</strong> Into the Peripheral Blood Following Chemotherapy most commonly used for<br />
<strong>and</strong> Cytokine Administration<br />
chemomobilisation include highdose<br />
cyclophosphamide <strong>and</strong><br />
etoposide. 22,25,38 Filgrastim<br />
(5 mcg/kg/day) can be utilised<br />
as the cytokine partner in<br />
chemomobilisation. 47 Because<br />
no single chemotherapy<br />
mobilisation regimen has<br />
demonstrated superiority over<br />
the others, some clinicians<br />
may elect to mobilise patients<br />
during a cycle of a diseasedirected<br />
chemotherapy regimen.<br />
G-CSF, granulocyte colony-stimulating factor.<br />
Examples of regimens utilised<br />
include cyclophosphamide,<br />
doxorubicin, vincristine, <strong>and</strong> prednisone (CHOP) <strong>and</strong> ifosfamide, carboplatin, <strong>and</strong> etoposide (ICE). 25 Additionally,<br />
the use of rituximab (a monoclonal antibody directed at cells that express CD20) prior to mobilisation<br />
has not demonstrated inferior yields of CD34+ cells; in fact, it may assist with decreasing the amount of<br />
tumour contamination in the collected product. 52,53 Adverse events associated with commonly employed<br />
chemotherapeutic agents used in mobilisation regimens are listed in Table 3. 54,55<br />
Table 3. Complications* Associated With Chemotherapeutic Agents Commonly Used for<br />
<strong>Mobilisation</strong> (Like Cyclophosphamide or Etoposide) 54,55<br />
Short-Term Side Effects<br />
• General malaise (weakness)<br />
• Infertility<br />
• GI symptoms (diarrhoea, nausea, vomiting, appetite loss, stomach discomfort<br />
or pain)<br />
• Skin <strong>and</strong> mucosal effects (rash, texture change in nails, alopecia, mucositis)<br />
• Myelosuppression (thrombocytopenia, leucopoenia)<br />
• Infusion-related side effects (such as hypotension, flushing, chest pain, fever,<br />
diaphoresis, cyanosis, urticaria, angio-oedema, <strong>and</strong> bronchospasm)<br />
• Allergic reaction<br />
• Signs of an infection, such as chills or a fever<br />
• Blood in the urine (may be a sign of bladder damage)<br />
• Blood in the stool<br />
GI, gastrointestinal.<br />
* Please see prescribing information for complete list of adverse reactions.<br />
Long-Term Side Effects<br />
• Decreased urination<br />
(may be a sign of kidney<br />
damage)<br />
• Difficulty breathing or<br />
water retention (which<br />
may be signs of congestive<br />
heart failure)<br />
• Secondary malignancies<br />
(may present as unusual<br />
moles, skin sores that<br />
do not heal, or unusual<br />
lumps)<br />
Chapter 2: <strong>Mobilisation</strong><br />
9
Plerixafor is a novel agent that has recently<br />
been approved in the European Union for use<br />
in conjunction with G-CSF in lymphoma <strong>and</strong><br />
multiple myeloma patients whose cells mobilise<br />
poorly, to mobilise stem cells from the bone<br />
marrow into the peripheral blood for collection<br />
<strong>and</strong> autologous transplantation. 56 Plerixafor<br />
is a small-molecule CXCR4 antagonist that<br />
reversibly inhibits the interaction between<br />
CXCR4 <strong>and</strong> SDF-1α (see plerixafor mechanism<br />
of action in Figure 8). 57-61 Use of plerixafor in<br />
combination with G-CSF has been shown to<br />
improve CD34+ cell collections in lymphoma<br />
<strong>and</strong> multiple myeloma patients compared<br />
to G-CSF alone. 30,62,63 Very common adverse<br />
reactions associated with the use of filgrastim,<br />
lenograstim, <strong>and</strong> plerixafor are listed in<br />
Table 4. 47,48,56,64<br />
Figure 8. Plerixafor Mechanism of Action 57-61<br />
An unfortunate outcome following HSC<br />
collections is poor stem cell yield. The<br />
most important risk factor for inadequate<br />
mobilisation is the amount of myelosuppressive<br />
chemotherapy a patient has received prior to<br />
collection. Agents that are toxic to stem cells, CXCR4, chemokine receptor 4; SDF-1α, stromal cell derived factor-1 alpha.<br />
such as cyclophosphamide (doses > 7.5 g/m 2 ),<br />
melphalan, carmustine, procarbazine, fludarabine, nitrogen mustard, chlorambucil, are particularly detrimental to<br />
stem cell collection yields. Other risk factors associated with low CD34+ cell collections are listed in Table 5. 25,65-73<br />
Table 4. Very Common (> 10%) Adverse Reactions* Associated With Agents Used in <strong>Stem</strong> <strong>Cell</strong><br />
<strong>Mobilisation</strong> 47,48,56,64<br />
Agent<br />
Adverse Events<br />
Filgrastim • Musculoskeletal pain<br />
Lenograstim • Bone <strong>and</strong> back pain<br />
• Leucocytosis <strong>and</strong> thrombocytopenia<br />
• Transient increases in liver function tests<br />
• Elevated LDH<br />
• Headache <strong>and</strong> aesthenia<br />
Plerixafor • Diarrhoea <strong>and</strong> nausea<br />
• Injection <strong>and</strong> infusion site reactions<br />
LDH, lactate dehydrogenase.<br />
* Please see summaries of product characteristics for complete lists of adverse reactions.<br />
10<br />
<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> <strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other Allied Health Care Professionals
Table 5. Risk Factors <strong>and</strong> Characteristics Associated With Poor Autologous <strong>Stem</strong> <strong>Cell</strong><br />
<strong>Mobilisation</strong> 25,65-73<br />
• Type <strong>and</strong> amount of chemotherapy administered to patient prior to mobilisation<br />
• Advanced age (> 60 years)<br />
• Multiple cycles of previous chemotherapy for treatment of underlying disease<br />
• Radiation therapy<br />
• Short time interval between chemotherapy <strong>and</strong> mobilisation<br />
• Extensive disease burden<br />
• Refractory disease<br />
• Tumour infiltration of the bone marrow<br />
• Prior use of lenalidomide<br />
• Evidence of poor marrow function (eg, low platelet <strong>and</strong> CD34+ cell blood count) at time of mobilisation<br />
Few options exist for patients who mobilise poorly, <strong>and</strong> st<strong>and</strong>ard management of these patients continues to<br />
evolve <strong>and</strong> remains ill-defined. Currently acceptable strategies for remobilisation involve increasing the doses<br />
of chemotherapy agents <strong>and</strong>/or cytokines, using a combination of cytokines, <strong>and</strong> extending the time between<br />
chemotherapy for disease treatment <strong>and</strong> apheresis. The option of performing a bone marrow harvest to collect<br />
cells is an alternative strategy. However, it is falling out of favour to previously mentioned methods due to<br />
slower engraftment, increased need for resource utilisation (longer hospitalisation <strong>and</strong> more supportive care<br />
management), <strong>and</strong> higher risk of mortality. 25,35,65,66,74-76 More promising is the use of newer <strong>and</strong> recently approved<br />
agents (such as plerixafor) as part of established mobilisation techniques to increase stem cell yields during<br />
collections. A comparison between mobilisation methods is listed in Table 6. 22,24,25,28,37-39<br />
Table 6. Comparison of <strong>Mobilisation</strong> Methods 22,24,25,28,37-39,77-81<br />
<strong>Mobilisation</strong> Regimen Characteristics<br />
Filgrastim or lenograstim • Low toxicity<br />
• Outpatient administration<br />
• Can be self-administered<br />
• Reasonable efficacy in most patients<br />
• Predictable mobilisation, permitting easy apheresis scheduling<br />
• Shorter time from administration to collection compared to<br />
growth factor + chemotherapy<br />
• Bone pain<br />
• Lower stem cell yield compared to growth factor + chemotherapy<br />
Filgrastim or lenograstim +<br />
chemotherapy<br />
Filgrastim or lenograstim +<br />
plerixafor<br />
• Higher stem cell yield compared to growth factor alone<br />
• Fewer stem cell collections<br />
• Potential for anticancer activity<br />
• May impair future mobilisation of stem cells<br />
• May require hospitalisation<br />
• Associated with an increased number of side effects<br />
• Inconsistent results<br />
• Longer time from administration to collection compared to growth factor<br />
• Low predictability of time to peak peripheral blood CD34+ cell levels<br />
• Low toxicity<br />
• Outpatient administration<br />
• Low failure rate<br />
• High probability of collecting optimal number of CD34+ cells<br />
• Efficacy in poor mobilisers<br />
• Predictable mobilisation permitting easy apheresis scheduling<br />
• Shorter time from administration to collection compared to<br />
growth factor + chemotherapy<br />
• Gastrointestinal adverse effects<br />
Chapter 2: <strong>Mobilisation</strong><br />
11
Chapter 3: <strong>Stem</strong> <strong>Cell</strong> Collection (<strong>Apheresis</strong>), Storage, <strong>and</strong> Reinfusion<br />
Prior to initiation of the stem cell collection process, patients must be thoroughly evaluated <strong>and</strong> determined<br />
to be acceptable transplant c<strong>and</strong>idates <strong>and</strong> able to tolerate all of the procedures involved. Some of the medical,<br />
nursing, <strong>and</strong> psychosocial evaluations can occur prior to a patient’s first visit or referral to a transplant service<br />
or clinic. The patient’s primary medical haematologist/oncologist frequently serves as a patient’s first contact<br />
during the transplantation process. All of the testing, evaluation, <strong>and</strong> education involved throughout a patient’s<br />
transplant involves a myriad of health care professionals working together to orchestrate this complex<br />
medical procedure.<br />
The medical pre-evaluation is the first step a patient must complete when undergoing an AHSCT. This involves<br />
the patient’s primary medical oncologist making a referral to a transplant centre or service. The physician provides<br />
the transplant team with information that often includes specifics relating to the care of the patient up to this<br />
time point, such as past medical history, cancer status, summary of cancer treatments <strong>and</strong> responses, <strong>and</strong><br />
complications experienced during therapy. Accompanying this information are any available radiograph <strong>and</strong><br />
laboratory testing results.<br />
After review of the patient’s medical information, the transplant team will initiate their own battery of tests <strong>and</strong><br />
evaluations to assess a patient’s eligibility to proceed with stem cell collection <strong>and</strong> transplantation. This involves<br />
restaging the patient to verify or establish current disease status, ascertaining the function of various organs<br />
(eg, kidneys, liver, <strong>and</strong> lungs), documenting the absence of certain comorbid conditions <strong>and</strong> infectious diseases<br />
(eg, congestive heart failure <strong>and</strong> the presence of human immunodeficiency virus), <strong>and</strong> evaluating the overall<br />
performance status <strong>and</strong> psychosocial condition of the patient. At this time, extensive education will be initiated<br />
for the patient <strong>and</strong> their family <strong>and</strong>/or caregivers. Often a member of the nursing profession (clinic nurse, nurse<br />
educator, or nurse coordinator) will coordinate the education process for the patient <strong>and</strong> those involved in their<br />
care (see Chapter 4).<br />
Upon determination that a patient is eligible to proceed to transplantation, preparing them for the collection<br />
process occurs next. The preferred method for venous access is the placement of a peripheral catheter at the<br />
time of an apheresis session (eg, insertion into the antecubital vein). For those patients in whom peripheral line<br />
placement is not feasible, appropriate catheter selection <strong>and</strong> central venous placement (eg, internal jugular<br />
vein) is scheduled prior to the first stem cell collection. Catheters used for apheresis procedures must be able<br />
to tolerate large fluctuations in circulating blood volume. Therefore, these catheters are often large-bore, double<br />
lumen devices that can be used temporarily during cell collections, or placed permanently <strong>and</strong> used throughout<br />
the transplantation process. As with most catheters placed in the area of the upper extremities, patients should<br />
be monitored for signs <strong>and</strong> symptoms of hypotension, shortness of breath, <strong>and</strong> decreased breath sounds as<br />
these can be indicative of venous wall perforation, haemothorax, <strong>and</strong>/or pneumothorax, all of which are rare<br />
but serious complications that can occur. In some cases, catheters for apheresis may be placed centrally in<br />
a femoral vein if patients are at an increased risk of developing complications from a catheter placed in the<br />
upper extremity or chest wall. For centrally placed catheters, radiographic evaluation is used to verify catheter<br />
placement prior to clearance for its use. Additionally, instructions on caring for the catheter to prevent infection<br />
<strong>and</strong> maintain its integrity should be extensively reviewed with the patient <strong>and</strong>/or caregivers. 1,2,16,82,83<br />
Chapter 3: Collection,<br />
Storage, <strong>and</strong> Reinfusion<br />
Preparation for stem cell collections in an apheresis centre or unit follows the pre-transplantation evaluation<br />
<strong>and</strong> catheter placement. Patients will be advised <strong>and</strong> counselled on therapies that they will receive during<br />
mobilisation with respect to administration schedule <strong>and</strong> expected adverse effects. As previously detailed in<br />
Chapter 2, agents used during this stage of AHSCT usually include single-agent cytokines (such as filgrastim)<br />
Chapter 3: <strong>Stem</strong> <strong>Cell</strong> Collection (<strong>Apheresis</strong>), Storage, <strong>and</strong> Reinfusion<br />
13
that are given with or without certain chemotherapy agents, a designated cycle of disease-specific chemotherapy<br />
regimen, or more recently, filgrastim or lenograstim in combination with plerixafor. Upon initiation of the<br />
mobilisation regimen, patients can expect to undergo their first apheresis session in as little as 4 to 5 days<br />
or, in some cases, 2 to 3 weeks later. 1,16,83 The extent of mobilisation is ascertained through evaluation of a<br />
patient’s WBC count. Serial measurements of the patient’s WBC count will assist the clinician in determining the<br />
appropriate time to commence collection procedures. Additionally, centres may use peripheral blood CD34+<br />
cell levels as a surrogate for mobilisation status. Established thresholds for apheresis initiation may vary across<br />
centres, but typically range from 5 to 20 CD34+ cells/microlitre. Although useful in estimating mobilisation<br />
efficacy, peripheral blood CD34+ counts can be variable within <strong>and</strong> across centres. 35,84,85<br />
Figure 9. Example of an <strong>Apheresis</strong> Machine Once mobilisation has reached an optimal level,<br />
a patient can be scheduled for sessions in the<br />
apheresis centre. An apheresis technician highly<br />
trained in stem cell collections is responsible<br />
for the equipment utilised in the collection<br />
process (Figure 9). Clinical nurses working in the<br />
apheresis unit are responsible for educating the<br />
patient about the stem cell collection process <strong>and</strong><br />
monitoring patients for any adverse reactions.<br />
Patients are connected to the apheresis machine<br />
by their catheter. One lumen is used to draw blood<br />
out of the patient <strong>and</strong> into the machine. Here the<br />
blood is spun at high speeds in a centrifugation<br />
chamber housed within the cell separator<br />
machine. The desired stem cells are collected<br />
during the entire procedure, either in cycles or<br />
continuously, <strong>and</strong> the remaining blood components<br />
are returned to the patient through the second<br />
lumen of their catheter. This second lumen<br />
additionally can be used to administer intravenous<br />
fluids, electrolyte supplements, <strong>and</strong> medications<br />
to the patient. Each apheresis session lasts<br />
approximately 2-5 hours during which upwards<br />
to 30 litres of blood, or 6 times the average total human blood volume, is processed. Collections can occur on a<br />
daily basis until the target CD34+ levels are achieved. The apheresis process can last for up to 4 days depending<br />
on patient characteristics <strong>and</strong> the mobilisation regimen utilised. 2,16,17,82,86-88<br />
<strong>Apheresis</strong> procedures are relatively safe. Although the mortality rate is quite low at an estimated 3 deaths<br />
per 10,000 procedures, 89 apheresis is associated with some morbidity. Citrate is an anticoagulant used during<br />
the apheresis process to prevent blood clotting. Thus, one of the most common adverse effects seen during<br />
this procedure is citrate toxicity manifested as hypocalcaemia. This occurs due to binding of ionised serum<br />
calcium, which leads to hypocalcaemia. Signs <strong>and</strong> symptoms of citrate toxicity as well as its management are<br />
further described in Table 7. Monitoring serum calcium level prior to <strong>and</strong> throughout apheresis may decrease<br />
the likelihood of hypocalcaemia. 16,82,90 Additional adverse effects of citrate toxicity include hypomagnesaemia,<br />
hypokalaemia, <strong>and</strong> metabolic alkalosis. Magnesium, like calcium, is a divalent ion that is bound by citrate.<br />
Declines in serum magnesium levels often are more pronounced <strong>and</strong> take longer to normalise compared to<br />
aberrations in calcium levels. Signs <strong>and</strong> symptoms of hypomagnesaemia, hypokalaemia, <strong>and</strong> metabolic alkalosis<br />
as well as their management are further described in Table 7. 16,82,90<br />
14<br />
<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> <strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other Allied Health Care Professionals
Table 7. Common <strong>Apheresis</strong> Complications 16,82,90<br />
Adverse Effect Cause Signs <strong>and</strong> Symptoms Corrective Action<br />
Citrate toxicity<br />
Anticoagulant (citrate)<br />
given during apheresis<br />
Hypocalcaemia<br />
Common: dizziness, tingling in area<br />
around the mouth, h<strong>and</strong>s, <strong>and</strong> feet<br />
Uncommon: chills, tremors, muscle<br />
twitching <strong>and</strong> cramps, abdominal<br />
cramps, tetany, seizure, cardiac<br />
arrhythmia<br />
Slow the rate of apheresis;<br />
increase the blood:citrate ratio;<br />
calcium replacement therapy<br />
Hypomagnesaemia<br />
Common: muscle spasm or weakness<br />
Uncommon: decrease in vascular tone;<br />
cardiac arrhythmia<br />
Hypokalaemia<br />
Common: weakness<br />
Uncommon: hypotonia <strong>and</strong> cardiac<br />
arrhythmia<br />
Metabolic alkalosis<br />
Common: worsening of hypocalcaemia<br />
Slow the rate of apheresis;<br />
increase the blood:citrate<br />
ratio; magnesium replacement<br />
therapy<br />
Slow the rate of apheresis;<br />
increase the blood:citrate ratio;<br />
potassium replacement therapy<br />
Slow the rate of apheresis;<br />
increase the blood:citrate ratio<br />
Thrombocytopenia<br />
Platelets adhere to<br />
internal surface of the<br />
apheresis machine<br />
Uncommon: decrease in respiration<br />
rate<br />
Low platelet count, bruising, bleeding<br />
Prime apheresis machine with<br />
blood products in place of normal<br />
saline; platelet transfusion<br />
Hypovolaemia<br />
Patient intolerant of<br />
large shift in extracorporeal<br />
blood <strong>and</strong> plasma<br />
volumes<br />
Dizziness, fatigue, light-headedness,<br />
tachycardia, hypotension, diaphoresis,<br />
cardiac arrhythmia<br />
Slow the rate of apheresis<br />
session or temporarily stop it;<br />
intravenous fluid boluses<br />
Catheter<br />
malfunction<br />
Blood clot forms or<br />
catheter is not well<br />
positioned to allow for<br />
adequate blood flow<br />
Inability to flush catheter, fluid collection<br />
under skin around catheter site;<br />
pain <strong>and</strong> erythema at catheter site; arm<br />
swelling, decrease in blood flow<br />
Reposition the catheter; gently<br />
flush catheter; treat blood clot<br />
Infection<br />
Microbial pathogens<br />
enter bloodstream<br />
through catheter or<br />
catheter site<br />
Fever, chills, fatigue, red <strong>and</strong><br />
erythematous skin around catheter;<br />
hypotension, positive blood cultures<br />
Administer antibiotics; possibly<br />
remove catheter<br />
Due to large fluctuations in blood volume during apheresis, patients may experience hypovolaemia. Signs<br />
<strong>and</strong> symptoms of hypovolaemia as well as its management are further described in Table 7. 16,82,90 Prior to<br />
starting apheresis, baseline pulse <strong>and</strong> blood pressure are measured <strong>and</strong> continuously assessed at regular<br />
intervals. Additionally, it is recommended that haemoglobin <strong>and</strong> haematocrit also be monitored. Patients at<br />
risk of developing hypovolaemia include those with anaemia, those with a previous history of cardiovascular<br />
compromise, <strong>and</strong> children or adults with a small frame. Preventative measures are aimed at minimising the<br />
extracorporeal volume shift by priming the apheresis machine with red blood cells <strong>and</strong> fresh frozen plasma in<br />
place of normal saline. Hypovolaemia may also be managed by providing intravenous fluid boluses <strong>and</strong> slowing<br />
the rate of flow on the apheresis machine. Another potential problem stemming from hypovolaemia is the<br />
development of a life-threatening cardiac dysrhythmia. If this occurs, apheresis should be interrupted <strong>and</strong><br />
symptoms should subside before proceeding with collections. 16,82,90<br />
Thrombocytopenia, infection, <strong>and</strong> catheter malfunction are other complications that may be encountered during<br />
stem cell collections. When the patient’s blood is in the cell separator machine, platelets can adhere to the<br />
centrifuge device. Decreases in platelet concentrations can be precipitous <strong>and</strong> obtaining platelet counts prior<br />
to each collection is essential. If thrombocytopenia is present pre-apheresis, patients may receive platelet<br />
Chapter 3: <strong>Stem</strong> <strong>Cell</strong> Collection (<strong>Apheresis</strong>), Storage, <strong>and</strong> Reinfusion<br />
15
transfusions. Additional management of thrombocytopenia during apheresis is the return of platelet-rich<br />
plasma collected during apheresis to the patient at the conclusion of the apheresis session. 2,16,82,90 As with any<br />
catheter, frequent manipulation in the absence of proper catheter care <strong>and</strong> maintenance may predispose the<br />
patient to infections <strong>and</strong>/or cause the catheter to malfunction. Proper sterile technique should be utilised at all<br />
times to decrease the risk of contamination with microbial pathogens that can lead to bloodstream infections.<br />
Furthermore, routine catheter care should include administration of flushes to prevent blood clot formation.<br />
Commonly observed complications during apheresis are summarised in Table 7. 1,2,16,82,83,90<br />
At the conclusion of apheresis, stem cells are isolated from red blood cells <strong>and</strong> WBCs <strong>and</strong> then placed in infusion<br />
bags in preparation for cryopreservation <strong>and</strong> storage. Many centres have cryopreservation laboratories that<br />
maintain collected stem cell products in liquid nitrogen until the time of the patient’s transplantation. A common<br />
cryopreservative used is dimethylsulfoxide (DMSO). DMSO maintains cell viability by preventing ice crystal<br />
formation within the cells during storage. 2,82,91 Additionally, the collected product may be manipulated by a<br />
pharmacological, immunological, or physical method to reduce contamination with tumour cells. Quality testing is<br />
performed on collections to ascertain contamination with microbes as well as to determine the number of viable<br />
cells available for transplantation. Once a patient reaches their CD34+ collection goal, apheresis sessions are<br />
complete. Reaching minimum thresholds for CD34+ cell amounts is important as cell dose appears to positively<br />
correlate with engraftment <strong>and</strong> outcome. 17,22,25,32-36,92<br />
The next stage of the AHSCT process is preparing the patient for the actual transplant. Nurses play an<br />
important role in educating patients <strong>and</strong> caregivers about the transplant processes <strong>and</strong> procedures as well<br />
as the critical time leading up to engraftment <strong>and</strong> recovery. Whereas some patients can expect to proceed to<br />
transplant within days following mobilisation, others may undergo the transplantation procedure within a few<br />
weeks following stem cell collection. During the interim, additional chemotherapy may be given to the patient<br />
to help maintain their disease status. Once the transplant date is scheduled, approximately 1 week prior to the<br />
transplant date, patients begin their preparative regimen in the ambulatory or inpatient unit of the hospital. The<br />
preparative regimens may consist of chemotherapy alone or chemotherapy in combination with radiation therapy.<br />
Chemotherapy agents selected for use during this time can be different than those used during previous cancer<br />
treatments <strong>and</strong> during mobilisation. Often, if similar agents are chosen, the doses during this phase are higher<br />
than previously administered. The patient often benefits from cytoreduction in their tumour following this<br />
phase of treatment. As a consequence of the intensity of treatment, patients experience ablation of their marrow<br />
stores, hence the need for infusion of their previously collected cells as “rescue” therapy. 1,2,16,82 Other expected<br />
sequelae from high-dose chemotherapy used in conjunction with AHSCT are summarised in Table 8. 1,2,16,82<br />
Table 8. Effects Following High-Dose Chemotherapy Used in AHSCT 1,2,16,82<br />
Organ Effects Interventions<br />
Gastrointestinal tract Nausea, vomiting, diarrhoea, anorexia,<br />
mucositis<br />
Antiemetics, mouth care regimens, pain<br />
medications, nutritional supplementation<br />
Blood components Pancytopenia Antibiotics, blood transfusions<br />
Kidneys Haemorrhagic cystitis Mesna, intravenous fluids, pain medications,<br />
bladder irrigation<br />
Liver<br />
Sinusoidal obstructive syndrome<br />
(veno-occlusive disease)<br />
Diuretics, fluid restriction, intensive supportive care<br />
Brain <strong>and</strong> nervous system Headache, tremors, seizures Pain medications, intensive supportive care<br />
Heart Oedema, hypertension Fluid restriction, diuretics, antihypertensive<br />
medications<br />
Lungs Atelectasis Pulmonary toilet<br />
Skin Rash, discoloration Topical emollients, skin care <strong>and</strong> bathing regimen<br />
AHSCT, autologous haematopoietic stem cell transplantation.<br />
16<br />
<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> <strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other Allied Health Care Professionals
Before high-dose chemotherapy is administered Figure 10. Storage of Collected <strong>Stem</strong> <strong>Cell</strong>s<br />
to the patient, the integrity of stored stem cells<br />
is verified. On the day of stem cell infusion, the<br />
previously collected product is removed from liquid<br />
nitrogen storage (Figure 10), thawed, <strong>and</strong> prepared<br />
for patient administration. 17 The infusion itself can<br />
occur in an ambulatory or hospital setting. Prior<br />
to infusion, the product is rigorously inspected<br />
<strong>and</strong> tested for quality control measures such as<br />
CD34+ cell counts <strong>and</strong> the presence of microbes.<br />
Several members of the health care team will also<br />
ensure that the product is the patient’s collected<br />
cells. The patient is prepared for the infusion by<br />
receiving premedications (eg, an antihistamine, an<br />
antipyretic), having their intravenous line equipped<br />
to receive the cells, <strong>and</strong> being placed on medical<br />
equipment to monitor their vital signs throughout<br />
the procedure. The actual time for infusion can<br />
vary based on the patient <strong>and</strong> the number of bags collected during apheresis, but typically ranges from 30 to<br />
120 minutes. Patients should be frequently monitored for adverse events during the infusion that may require<br />
adjustment of the infusion rate for the product. Resuscitative equipment should be readily available should a<br />
medical emergency occur. 1,2,16,82 Frequently encountered reactions during autologous stem cell infusions are<br />
listed in Table 9. 1,2,16,82<br />
Table 9. Complications Associated With Autologous <strong>Stem</strong> <strong>Cell</strong> Infusion 1,2,16,82<br />
Adverse Effect Signs <strong>and</strong> Symptoms Corrective Action<br />
Reactions to DMSO Common: nausea, vomiting, abdominal cramping, headache,<br />
garlic aftertaste<br />
Treatment of symptoms<br />
Rare: Hypotension, rapid heart rate, shortness of breath,<br />
fever, neurologic complications<br />
Oedema Fluid retention, puffiness, weight gain, hypertension Diuretics, fluid restriction<br />
Contamination of<br />
stem cell product<br />
DMSO, dimethylsulfoxide.<br />
Hypotension, rapid heart rate, shortness of breath, fever,<br />
chills, rigors, positive blood culture for microbial pathogen<br />
Antibiotics, intensive supportive<br />
care<br />
The last component of AHSCT is engraftment <strong>and</strong> recovery. During this critical time, the infused stem cells find<br />
their way back to the bone marrow microenvironment <strong>and</strong> repopulate depleted marrow stores. Post-transplant,<br />
cytokines are administered to enhance stem cell maturation <strong>and</strong> to re-establish blood cell components. The<br />
first sign of engraftment is the return of circulating WBCs to a sufficient level defined as an absolute neutrophil<br />
count (ANC) of > 500/mm 3 for 3 consecutive days, which typically occurs 7-14 days after the stem cells have<br />
been infused into the patient. 1,2 Increased platelet levels (absent of transfusion support) is another indicator<br />
of recovery, <strong>and</strong> occurs at a later time point, averaging 2-3 weeks following the transplant. 1,2 Until engraftment<br />
occurs, patients are at an increased risk of infections, so precautions must be taken to avoid exposure to<br />
microbial pathogens. Patients often require supportive care strategies <strong>and</strong> therapies, including administration of<br />
antiemetics, pain medications, antibiotics, <strong>and</strong> nutrition support to ameliorate consequences following the highdose<br />
chemotherapy preparative regimen <strong>and</strong> the subsequent prolonged period of pancytopenia. 1,2,16,82<br />
Chapter 3: <strong>Stem</strong> <strong>Cell</strong> Collection (<strong>Apheresis</strong>), Storage, <strong>and</strong> Reinfusion<br />
17
1<br />
4<br />
Chapter 4: How to Discuss Noted Topics With Patients<br />
Stage Heading<br />
Some of the most important nursing<br />
contributions throughout the AHSCT process<br />
are patient education <strong>and</strong> psychosocial<br />
support to patients <strong>and</strong> their families.<br />
Opportunities for teaching are many, from<br />
describing research protocols to explaining<br />
medical procedures <strong>and</strong> therapies; nurses<br />
in a variety of positions have the expertise<br />
to guide patients throughout the process.<br />
Education about AHSCT should begin prior<br />
to the initial referral for transplantation <strong>and</strong><br />
continue throughout the indicated followup<br />
period after transplantation. Imparting<br />
knowledge to patients <strong>and</strong> caregivers not<br />
only eases fears <strong>and</strong> concerns (Table 10),<br />
but it makes individuals feel empowered in<br />
making the best decisions for themselves<br />
or their loved ones. The education given<br />
to patients can occur through a variety of<br />
methods, including explanations <strong>and</strong> demonstrations, <strong>and</strong> it is frequently repeated to ensure underst<strong>and</strong>ing.<br />
Media to assist patient <strong>and</strong> caregiver comprehension includes written materials, videos, <strong>and</strong> group teaching<br />
exercises. Table 11 lists key teaching points nurses often provide patients <strong>and</strong> their caregivers during the AHSCT<br />
This is where a description would go as needed<br />
Stage Heading<br />
process. 1,2,16,82,93<br />
Table 10. Sources for Concern Experienced by Patients <strong>and</strong> Caregivers During AHSCT<br />
LOREM IPSUM<br />
• Ability of the patient to tolerate the procedures surrounding AHSCT<br />
STEM CELL<br />
• Ability of the patient to collect sufficient stem cells to proceed with transplant<br />
COLLECTION<br />
• Likelihood of disease relapse after AHSCT<br />
• Response to additional treatment in the setting of disease relapse or poor mobilisation<br />
• Life expectancy of the patient<br />
• Maintaining regularly scheduled appointments for clinic visits <strong>and</strong> diagnostic procedures<br />
• Secondary complications as a result of AHSCT <strong>and</strong> their treatment<br />
• Required lifestyle changes <strong>and</strong> their impacts<br />
• Ability to pay for procedures, treatments, <strong>and</strong> ancillary expenses (eg, temporary housing, transportation between<br />
home <strong>and</strong> treating facility, child care)<br />
• Ability to maintain employment during treatment <strong>and</strong>/or resume employment after therapy<br />
• Ability to maintain social, physical, <strong>and</strong>/or emotional relationships with others<br />
This • is Psychological where well-being a description of oneself <strong>and</strong> loved would ones go as needed<br />
Chapter 4: Patient Topics<br />
AHSCT, autologous haematopoietic stem cell transplantation.<br />
Chapter 4: How to Discuss Noted Topics With Patients<br />
19
Table 11. Key Teaching Points for Nurses Involved in Caring for AHSCT Patients 1,2,16,82,93<br />
Stage of AHSCT<br />
Prior <strong>and</strong> up to the<br />
time of referral for<br />
transplantation<br />
Pre-transplantation<br />
evaluation<br />
Educational Opportunities<br />
• General overview of the entire transplantation procedure<br />
• Caregiver roles <strong>and</strong> responsibilities during the procedure<br />
• Introduction to members of the transplant team <strong>and</strong> explanation of each of their roles<br />
in patient care<br />
• Overview of the transplant clinic, including hours of operation<br />
• Explanation of all laboratory tests, scans, <strong>and</strong> procedures needed for work-up<br />
• Detailed explanation of transplant procedure, including common complications<br />
• Resources available to patients <strong>and</strong> caregivers to assist with psychosocial support <strong>and</strong><br />
coping mechanisms<br />
• Catheter placement <strong>and</strong> care during transplantation <strong>and</strong> apheresis<br />
<strong>Mobilisation</strong> <strong>and</strong><br />
apheresis<br />
• How <strong>and</strong> when to administer agents used in the mobilisation process<br />
• Schedule of chemotherapy used in the mobilisation process<br />
• What medications a patient should <strong>and</strong> should not take during mobilisation<br />
• Expected adverse effects <strong>and</strong> their management for all agents used in mobilisation<br />
• Review of care of catheter used for apheresis<br />
• Explanation of apheresis procedure<br />
• Expected adverse effects from apheresis procedure<br />
• Importance of laboratory monitoring <strong>and</strong> how to manage electrolyte imbalances<br />
• <strong>Stem</strong> cell collection target level<br />
• Options for patients who mobilise poorly or fail to mobilise<br />
Preparative regimen • Treatment plan <strong>and</strong> schedule of conditioning chemotherapy, including expected adverse<br />
effects <strong>and</strong> how to manage them<br />
• Review of supportive care medications that may be used during this time<br />
• Preventative measures for development of infections<br />
<strong>Stem</strong> cell infusion • Process for thawing <strong>and</strong> infusing stem cells<br />
• Potential complications following infusion of cells <strong>and</strong> how these effects are managed<br />
• How patient will be monitored during the infusion <strong>and</strong> thereafter<br />
Engraftment <strong>and</strong> recovery • Monitoring parameters <strong>and</strong> laboratory testing used to assess patient status<br />
• Reinforcement of neutropenic precautions<br />
• Signs <strong>and</strong> symptoms of infection <strong>and</strong> treatments available to manage patients<br />
• Significance of blood counts <strong>and</strong> how engraftment <strong>and</strong> recovery are determined<br />
• Other expected complications following transplantation <strong>and</strong> their management<br />
• Discharge planning process<br />
• Discharge medication education with respect to how to take medications at home <strong>and</strong><br />
expected adverse effects<br />
• Any necessary lifestyle changes<br />
Monitoring <strong>and</strong> follow-up • Clinic appointment schedule<br />
• How to monitor progress at home <strong>and</strong> when it is necessary to contact a health care<br />
professional<br />
• Long-term sequelae following transplantation <strong>and</strong> secondary complications<br />
• Risk <strong>and</strong> management of relapsed disease<br />
AHSCT, autologous haematopoietic stem cell transplantation.<br />
20<br />
<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> <strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other Allied Health Care Professionals
Initial teaching about AHSCT ideally begins at the time of the initial diagnosis of cancer or other disease.<br />
Although some patients may not proceed to AHSCT, possession of basic knowledge of state-of-the-art treatment<br />
throughout their continuum of care will empower the patient to make difficult decisions. The nurses in the<br />
medical haematology/oncology clinic or unit should assist patients in underst<strong>and</strong>ing what role, if any, an AHSCT<br />
has in their care. This is the time to introduce basic concepts of the mobilisation procedures, the stem cell<br />
transplant, <strong>and</strong> the period following transplantation.<br />
Once a patient is evaluated in a transplant centre, they will meet nurses who have different roles within<br />
the transplant programme. For example, a nurse coordinator is responsible for directing the pre-transplant<br />
preparation through the coordination of medical testing <strong>and</strong> evaluation. The nurse coordinator collaborates<br />
with clinic nurses to educate patients <strong>and</strong> their families, giving them an overview of the clinic operations <strong>and</strong><br />
detailed explanations of the procedures surrounding the transplantation process. After a patient is approved<br />
for the transplantation, nurses in the clinic will assist with coordinating care with the apheresis centre,<br />
including scheduling appropriate catheter placement <strong>and</strong> providing any associated teaching. The nurses also<br />
assist with any psychosocial needs <strong>and</strong> make referrals to other members of the team as necessary (eg, social<br />
workers). Nurses should also encourage patients <strong>and</strong> their caregivers to achieve their own educational goals by<br />
encouraging them to ask the medical team any questions they may have prior to initiating any procedures.<br />
During mobilisation <strong>and</strong> apheresis, nurses will remain in close contact with patients <strong>and</strong> their families,<br />
communicating information regarding follow-up for apheresis procedures, total CD34+ counts post-apheresis,<br />
<strong>and</strong> the next phase of the plan of care. Prior to starting apheresis, adverse effects of this procedure are<br />
explained as well as the management of their central venous catheters. It is important for nurses to recognise<br />
patients at greatest risk of poor mobilisation. In such instances, nurses should possess basic knowledge about<br />
remobilisation strategies <strong>and</strong> how to proceed with treatment <strong>and</strong>, moreover, whether AHSCT will be a treatment<br />
option. If the nurse can confidently discuss potential options, the patient <strong>and</strong> their family members may have<br />
greater confidence that the nurse is their advocate, thus reducing any additional fears <strong>and</strong> stressors.<br />
The provision of care surrounding the actual stem cell transplant, including administration of the preparative<br />
regimen, the stem cell infusion, <strong>and</strong> supporting the patient through engraftment <strong>and</strong> recovery create<br />
opportunities for nurses to provide patients some of the most intensive <strong>and</strong> extensive education during the<br />
multiple processes involved in AHSCT. Numerous medications are utilised during this time period, most of<br />
which have the potential for serious adverse effects <strong>and</strong>/or drug interactions. It is not unusual for patients<br />
to experience times of extreme debilitation <strong>and</strong> emotional exhaustion. Nurses can expect to assist with the<br />
management of adverse effects through supportive care mechanisms <strong>and</strong> be attentive to the concerns <strong>and</strong><br />
anxiety expressed by patients <strong>and</strong> caregivers. Following recovery from transplantation, nurses continue to<br />
support patients through the discharge process, preparing them for the transition of care into the home setting.<br />
Even after the patient has recovered from the transplant, the educational role of the nurse continues. Patients<br />
continue to need counselling <strong>and</strong> guidance about lifestyle changes <strong>and</strong> when resumption of pre-transplant<br />
activities can be expected. An underst<strong>and</strong>ing of routine follow-up visits <strong>and</strong> medical surveillance are essential for<br />
positive patient outcomes. Long-term sequelae from chemotherapy <strong>and</strong> other treatment modalities should be a<br />
part of the educational process during the post-transplant period. It is also prudent to discuss the possibility of<br />
disease relapse with patients <strong>and</strong> how management of their disease will be h<strong>and</strong>led should this occur. Overall,<br />
nursing education administered to the transplant recipient is a complex <strong>and</strong> dynamic process that should be<br />
personalised to the patient’s disease, treatment plan, cognitive level, <strong>and</strong> psychosocial needs.<br />
Chapter 4: How to Discuss Noted Topics With Patients<br />
21
Glossary<br />
Allogeneic: refers to 2 different persons who do not share the same genetic composition<br />
Adaptive immunity: function of the immune system that is highly specific <strong>and</strong> is acquired through exposure to<br />
specific antigens<br />
<strong>Apheresis</strong>: the process of removing blood from an individual, separating cellular components, <strong>and</strong> then<br />
returning remaining portions back to the donor<br />
Autologous: refers to when one is both the donor <strong>and</strong> the recipient<br />
Autologous haematopoietic stem cell transplantation: medical procedure involving the collection <strong>and</strong><br />
storage of a person’s blood stem cells followed by administration of high dose chemotherapy <strong>and</strong>/or radiation<br />
therapy with subsequent reinfusion of stem cells to restore normal blood cell production<br />
Chemokines: a subset of cytokines that serve as chemoattractants responsible for guiding the migration of<br />
cells<br />
Chemomobilisation: the process of mobilising stem cells from the bone marrow into the peripheral blood<br />
through the use of chemotherapy in conjunction with one or more cytokines such as filgrastim<br />
Cryopreservation: the process of storing cells, tissues, or organs by a cooling mechanism that maintains the<br />
viability of the product for later use<br />
Cryopreservative: also known as cryoprotectant; a substance added to collected cells prior to storage to<br />
prevent dehydration or the formation of ice crystals that can decrease the viability of the product upon thawing.<br />
An example is dimethylsulfoxide (DMSO)<br />
Cytokines: small proteins released by cells that facilitate cellular behaviour as well as communication <strong>and</strong><br />
interaction between cells<br />
Cytoreduction: the reduction in the number of cancer cells<br />
Engraftment: when infused stem cells begin to proliferate <strong>and</strong> make new blood cellular components. Often this<br />
is defined in relation to minimum levels for neutrophil <strong>and</strong> platelet counts<br />
Haematopoiesis: the process of producing new blood cell components<br />
Haemostasis: regulation of the blood system to maintain stable, constant conditions relating to bleeding <strong>and</strong><br />
clotting<br />
Innate immunity: function of the immune system that is nonspecific, naturally present, <strong>and</strong> does not rely on<br />
prior exposure to an antigen<br />
<strong>Mobilisation</strong>: the process of increasing the number of stem cells from the bone marrow into the peripheral<br />
circulation prior to collection<br />
Monoclonal antibody: a type of antibody produced from a single clone of immune cells<br />
Myelosuppression: the inhibition of bone marrow activity often resulting in decreased production of blood<br />
components<br />
Pancytopenia: a decrease in all types of blood cells, including white blood cells, red blood cells, <strong>and</strong> platelets<br />
Pluripotent: describes cells that have the ability to self-replicate <strong>and</strong> the potential to differentiate into specific<br />
cell types<br />
Progenitor: a precursor or original cell that may or may not be capable of self-renewal<br />
Remobilisation: the process of mobilisation after failure from a previous attempt<br />
Rituximab: a chimeric monoclonal antibody that binds to CD20 protein on the surface of cells<br />
Stromal: refers to the stroma; the stroma is the supportive framework of tissue that usually comprises<br />
connective tissue<br />
Syngeneic: refers to 2 different persons with the exact genetic composition (ie, identical twins)<br />
T<strong>and</strong>em autologous stem cell transplantation: process in which a person receives 2 scheduled,<br />
sequential transplants with their own stem cells collected prior to the first transplant<br />
Glossary<br />
23<br />
Glossary, References,<br />
<strong>and</strong> Additional Resources
References<br />
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bone marrow in patients with malignant lymphoma. Blood. 1978;52(1):85-95.<br />
5. Armitage JO. The history of autologous hematopoietic cell transplantation. In: Applebaum FR, Forman SJ, Negrin RS, Blume KG,<br />
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12. Linch DC, Winfield D, Goldstone AH, et al. Dose intensification with autologous bone-marrow transplantation in relapsed <strong>and</strong><br />
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24<br />
<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> <strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other Allied Health Care Professionals
33. Scheid C, Draube A, Reiser M, et al. Using at least 5x10(6)/kg CD34+ cells for autologous stem cell transplantation significantly<br />
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45. Heissig B, Hattori K, Dias S, et al. Recruitment of stem <strong>and</strong> progenitor cells from the bone marrow niche requires MMP-9<br />
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46. Levesque JP, Takamatsu Y, Nilsson SK, Haylock DN, Simmons PJ. Vascular cell adhesion molecule-1 (CD106) is cleaved by<br />
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factor. Blood. 2001;98(5):1289-1297.<br />
47. Neupogen ® (filgrastim) [summary of product characteristics]. Cambridge, United Kingdom: Amgen Ltd; 2009. Please refer to the<br />
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49. Kroger N, Renges H, Kruger W, et al. A r<strong>and</strong>omized comparison of once versus twice daily recombinant human granulocyte<br />
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50. Kim S, Kim HJ, Park JS, et al. Prospective r<strong>and</strong>omized comparative observation of single- vs split-dose lenograstim to mobilize<br />
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51. Komeno Y, K<strong>and</strong>a Y, Hamaki T, et al. A r<strong>and</strong>omized controlled trial to compare once- versus twice-daily filgrastim for mobilization<br />
of peripheral blood stem cells from healthy donors. Biol Blood Marrow Transplant. 2006;12(4):408-413.<br />
52. Flinn IW, O’Donnell PV, Goodrich A, et al. Immunotherapy with rituximab during peripheral blood stem cell transplantation for<br />
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53. Naparstek E. The role of the anti-CD20 antibody rituximab in hematopoietic stem cell transplantation for non-Hodgkin’s<br />
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54. Cytoxan ® (cyclophosphamide injection) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; 2005.<br />
55. Etoposide injection [prescribing information]. Bedford, OH: Bedford Laboratories; 2008.<br />
56. Mozobil ® (plerixafor) [summary of product characteristics]. Naarden, The Netherl<strong>and</strong>s: Genzyme Europe B.V.; 2009. Please refer<br />
to the applicable national summary of product characteristics.<br />
57. Martin C, Bridger GJ, Rankin SM. Structural analogues of AMD3100 mobilise haematopoietic progenitor cells from bone marrow<br />
in vivo according to their ability to inhibit CXCL12 binding to CXCR4 in vitro. Br J Haematol. 2006;134(3):326-329.<br />
58. Hatse S, Princen K, Bridger G, De Clercq E, Schols D. Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4.<br />
FEBS Lett. 2002;527(1-3):255-262.<br />
59. Fricker SP, Anastassov V, Cox J, et al. Characterization of the molecular pharmacology of AMD3100: a specific antagonist of the<br />
G-protein coupled chemokine receptor, CXCR4. Biochem Pharmacol. 2006;72(5):588-596.<br />
60. Gerlach LO, Skerlj RT, Bridger GJ, Schwartz TW. Molecular interactions of cyclam <strong>and</strong> bicyclam non-peptide antagonists with the<br />
CXCR4 chemokine receptor. J Biol Chem. 2001;276(17):14153-14160.<br />
61. Broxmeyer HE, Orschell CM, Clapp DW, et al. Rapid mobilization of murine <strong>and</strong> human hematopoietic stem <strong>and</strong> progenitor cells<br />
with AMD3100, a CXCR4 antagonist. J Exp Med. 2005;201(8):1307-1318.<br />
62. Devine SM, Flomenberg N, Vesole DH, et al. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist<br />
AMD3100 to patients with multiple myeloma <strong>and</strong> non-Hodgkin’s lymphoma. J Clin Oncol. 2004;22(6):1095-1102.<br />
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63. Cal<strong>and</strong>ra G, McCarty J, McGuirk J, et al. AMD3100 plus G-CSF can successfully mobilize CD34+ cells from non-Hodgkin’s<br />
lymphoma, Hodgkin’s disease <strong>and</strong> multiple myeloma patients previously failing mobilization with chemotherapy <strong>and</strong>/or cytokine<br />
treatment: compassionate use data. Bone Marrow Transplant. 2008;41(4):331-338.<br />
64. Neupogen ® (filgrastim) [package insert]. Thous<strong>and</strong> Oaks, CA: Amgen Inc; 2007.<br />
65. Stiff PJ. Management strategies for the hard-to-mobilize patient. Bone Marrow Transplant. 1999;23 Suppl 2:S29-33.<br />
66. Micallef IN, Apostolidis J, Rohatiner AZ, et al. Factors which predict unsuccessful mobilisation of peripheral blood progenitor cells<br />
following G-CSF alone in patients with non-Hodgkin’s lymphoma. Hematol J. 2000;1(6):367-373.<br />
67. Bensinger W, Appelbaum F, Rowley S, et al. Factors that influence collection <strong>and</strong> engraftment of autologous peripheral-blood stem<br />
cells. J Clin Oncol. 1995;13(10):2547-2555.<br />
68. Hosing C, Saliba R, Ahlawat S, et al. Poor hematopoietic stem cell mobilizers: a single institution study of incidence <strong>and</strong> risk<br />
factors in patients with recurrent or relapsed lymphoma. Am J Hematol. 2009;84(6):335-337.<br />
69. Demirer T, Buckner CD, Gooley T, et al. Factors influencing collection of peripheral blood stem cells in patients with multiple<br />
myeloma. Bone Marrow Transplant. 1996;17(6):937-941.<br />
70. Paripati H, Stewart AK, Cabou S, et al. Compromised stem cell mobilization following induction therapy with lenalidomide in<br />
myeloma. Leukemia. 2008;22(6):1282-1284.<br />
71. Popat U, Saliba R, Th<strong>and</strong>i R, et al. Impairment of filgrastim-induced stem cell mobilization after prior lenalidomide in patients with<br />
multiple myeloma. Biol Blood Marrow Transplant. 2009;15(6):718-723.<br />
72. Fruehauf S, Haas R, Conradt C, et al. Peripheral blood progenitor cell (PBPC) counts during steady-state hematopoiesis allow to<br />
estimate the yield of mobilized PBPC after filgrastim (R-metHuG-CSF)-supported cytotoxic chemotherapy. Blood. 1995;85(9):2619-<br />
2626.<br />
73. Fruehauf S, Schmitt K, Veldwijk MR, et al. Peripheral blood progenitor cell (PBPC) counts during steady-state haemopoiesis<br />
enable the estimation of the yield of mobilized PBPC after granulocyte colony-stimulating factor supported cytotoxic<br />
chemotherapy: an update on 100 patients. Br J Haematol. 1999;105(3):786-794.<br />
74. Goterris R, Hern<strong>and</strong>ez-Boluda JC, Teruel A, et al. Impact of different strategies of second-line stem cell harvest on the outcome<br />
of autologous transplantation in poor peripheral blood stem cell mobilizers. Bone Marrow Transplant. 2005;36(10):847-853.<br />
75. Jantunen E, Kuittinen T. Blood stem cell mobilization <strong>and</strong> collection in patients with lymphoproliferative diseases: practical issues.<br />
Eur J Haematol. 2008;80(4):287-295.<br />
76. Seshadri T, Al-Farsi K, Stakiw J, et al. G-CSF-stimulated BM progenitor cells supplement suboptimal peripheral blood<br />
hematopoietic progenitor cell collections for auto transplantation. Bone Marrow Transplant. 2008;42(11):733-737.<br />
77. Hicks ML, Lonial S, Langston A, et al. Optimizing the timing of chemotherapy for mobilizing autologous blood hematopoietic<br />
progenitor cells. Transfusion. 2007;47(4):629-635.<br />
78. Bargetzi MJ, Passweg J, Baertschi E, et al. Mobilization of peripheral blood progenitor cells with vinorelbine <strong>and</strong> granulocyte<br />
colony-stimulating factor in multiple myeloma patients is reliable <strong>and</strong> cost effective. Bone Marrow Transplant. 2003;31(2):99-103.<br />
79. Seggewiss R, Buss EC, Herrmann D, Goldschmidt H, Ho AD, Fruehauf S. Kinetics of peripheral blood stem cell mobilization<br />
following G-CSF-supported chemotherapy. <strong>Stem</strong> <strong>Cell</strong>s. 2003;21(5):568-574.<br />
80. DiPersio JF, Micallef I, Stiff PJ, et al. Phase III prospective r<strong>and</strong>omized double-blind placebo-controlled trial of plerixafor plus<br />
granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem cell<br />
mobilization <strong>and</strong> transplantation in patients with non-Hodgkin’s lymphoma. J Clin Oncol. 2009;Aug 31 [epub ahead of print].<br />
81. Dipersio JF, Stadtmauer EA, Nademanee A, et al. Plerixafor <strong>and</strong> G-CSF versus placebo <strong>and</strong> G-CSF to mobilize hematopoietic stem<br />
cells for autologous stem cell transplantation in patients with multiple myeloma. Blood. 2009;113(23):5720-5726.<br />
82. Buchsel PC, Leum E, R<strong>and</strong>olph SR. Nursing care of the blood cell transplant recipient. Semin Oncol Nurs. 1997;13(3):172-183.<br />
83. Reddy RL. Mobilization <strong>and</strong> collection of peripheral blood progenitor cells for transplantation. Transfus Apher Sci. 2005;32(1):63-72.<br />
84. Perez-Simon JA, Caballero MD, Corral M, et al. Minimal number of circulating CD34+ cells to ensure successful leukapheresis<br />
<strong>and</strong> engraftment in autologous peripheral blood progenitor cell transplantation. Transfusion. 1998;38(4):385-391.<br />
85. Basquiera AL, Abichain P, Damonte JC, et al. The number of CD34(+) cells in peripheral blood as a predictor of the CD34(+) yield<br />
in patients going to autologous stem cell transplantation. J Clin Apher. 2006;21(2):92-95.<br />
86. Cassens U, Barth IM, Baumann C, et al. Factors affecting the efficacy of peripheral blood progenitor cells collections by largevolume<br />
leukaphereses with st<strong>and</strong>ardized processing volumes. Transfusion. 2004;44(11):1593-1602.<br />
87. Gasova Z, Marinov I, Vodvarkova S, Bohmova M, Bhuyian-Ludvikova Z. PBPC collection techniques: st<strong>and</strong>ard versus large volume<br />
leukapheresis (LVL) in donors <strong>and</strong> in patients. Transfus Apher Sci. 2005;32(2):167-176.<br />
88. Arslan O, Moog R. Mobilization of peripheral blood stem cells. Transfus Apher Sci. 2007;37(2):179-185.<br />
89. Smith DM, Ness MJ, L<strong>and</strong>mark JD, Haire WW, Kessinger A. Recurrent neurologic symptoms during peripheral stem cell apheresis<br />
in two patients with intracranial metastases. J Clin Apher. 1990;5(2):70-73.<br />
90. Winters JL. Complications of donor apheresis. J Clin Apher. 2006;21(2):132-141.<br />
91. Gorlin J. <strong>Stem</strong> cell cryopreservation. J Infus Chemother. 1996;6(1):23-27.<br />
92. Feugier P, Bensoussan D, Girard F, et al. Hematologic recovery after autologous PBPC transplantation: importance of the number<br />
of postthaw CD34+ cells. Transfusion. 2003;43(7):878-884.<br />
93. Ford RC, Wickline MM. Nursing role in hematopoietic cell transplantation. In: Appelbaum F, Forman SJ, Negrin RS, Blume KG, eds.<br />
Thomas’ Hematopoietic <strong>Cell</strong> Transplantation. Hoboken, NJ: Wiley-Blackwell; 2009:461-477.<br />
26<br />
<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> <strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other Allied Health Care Professionals
Additional Resources<br />
• American Cancer Society: http://www.cancer.org<br />
• American Society for Blood <strong>and</strong> Marrow Transplantation (ASMBT): http://www.asbmt.org<br />
• American Society for <strong>Apheresis</strong> (ASFA): http://www.apheresis.org<br />
• Blood <strong>and</strong> Marrow Transplant Information Network (BMT InfoNet): http://www.bmtinfonet.org<br />
• Cancerworld: http://www.cancerworld.org<br />
• Center for International Blood <strong>and</strong> Marrow Transplant Research (CIBMTR): http://www.cibmtr.org<br />
• The European Group for Blood & Marrow Transplantation (<strong>EBMT</strong>): http://www.ebmt.org<br />
• International Myeloma Foundation: http://myeloma.org<br />
• LeukemiaNet: http://www.leukemia-net.org<br />
• Leukemia <strong>and</strong> Lymphoma Society: http://www.leukemia-lymphoma.org<br />
• Leukemia Research Foundation: http://www.leukemia-research.org<br />
• Lymphomainfo.net: http://www.lymphomainfo.net<br />
• Lymphoma Coalition: http://www.lymphomacoalition.org<br />
• Lymphoma Forum <strong>and</strong> Lymphoma Association: http://www.lymphoma.org.uk<br />
• Lymphoma Research Foundation: http://www.lymphoma.org<br />
• Myeloma Euronet: http://www.myeloma-euronet.org<br />
• Multiple Myeloma Research Foundation: http://www.multiplemyeloma.org<br />
• National Bone Marrow Transplant Link (NBMT Link): http://www.nbmtlink.org<br />
• National Cancer Institute: http://www.cancer.gov<br />
• National Marrow Donor Program: http://www.marrow.org<br />
Additional Resources<br />
27
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<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> <strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other Allied Health Care Professionals
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30<br />
<strong>Haematopoietic</strong> <strong>Stem</strong> <strong>Cell</strong> <strong>Mobilisation</strong> <strong>and</strong> <strong>Apheresis</strong>:<br />
A Practical Guide for Nurses <strong>and</strong> Other Allied Health Care Professionals
This brochure was made possible by a<br />
financial contribution from<br />
Genzyme Europe B.V.