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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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2. Kapustay PM. Blood cell transplantation: concepts <strong>and</strong> concerns. Semin Oncol Nurs. 1997;13(3):151-163.<br />

3. Quine WE. The remedial application of bone marrow. JAMA. 1896;26(21):1012-1013.<br />

4. Appelbaum FR, Herzig GP, Ziegler JL, Graw RG, Levine AS, Deisseroth AB. Successful engraftment of cryopreserved autologous<br />

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 />

eds. Thomas’ Hematopoietic <strong>Cell</strong> Transplantation. Hoboken, NJ: Wiley-Blackwell; 2009:8-14.<br />

6. National Cancer Institute. Bone marrow transplantation <strong>and</strong> peripheral blood stem cell transplantation fact sheet. Available at:<br />

http://cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant. Accessed July 7, 2009.<br />

7. Attal M, Harousseau JL, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J<br />

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8. Ljungman P, Bregni M, Brune M, et al. Allogeneic <strong>and</strong> autologous transplantation for haematological diseases, solid tumours <strong>and</strong><br />

immune disorders: current practice in Europe 2009. Bone Marrow Transplant. 2009 Jul 6. [Epub ahead of print].<br />

9. Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in<br />

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10. Barlogie B, Alexanian R, Smallwood L, et al. Prognostic factors with high-dose melphalan for refractory multiple myeloma. Blood.<br />

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11. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, r<strong>and</strong>omized trial of autologous bone marrow transplantation <strong>and</strong><br />

chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med. 1996;335(2):91-97.<br />

12. Linch DC, Winfield D, Goldstone AH, et al. Dose intensification with autologous bone-marrow transplantation in relapsed <strong>and</strong><br />

resistant Hodgkin’s disease: results of a BNLI r<strong>and</strong>omised trial. Lancet. 1993;341(8852):1051-1054.<br />

13. Schmitz N, Pfistner B, Sextro M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with<br />

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14. Rabinowe SN, Soiffer RJ, Gribben JG, et al. Autologous <strong>and</strong> allogeneic bone marrow transplantation for poor prognosis patients<br />

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15. Khouri IF, Keating MJ, Vriesendorp HM, et al. Autologous <strong>and</strong> allogeneic bone marrow transplantation for chronic lymphocytic<br />

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16. Hooper PJ, Santas EJ. Peripheral blood stem cell transplantation. Oncol Nurs Forum. 1993;20(8): quiz 1222-3.<br />

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18. Spurr EE, Wiggins NE, Marsden KA, Lowenthal RM, Ragg SJ. Cryopreserved human haematopoietic stem cells retain engraftment<br />

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20. Montiel MM. Bone marrow. In: Harmening D, ed. Clinical Hematology <strong>and</strong> Fundamentals of Hemostasis. Philadelphia, PA: F.A.<br />

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21. Bell A, Hughes V. Hematopoiesis: morphology of human blood <strong>and</strong> marrow cells. In: Harmening D, ed. Clinical Hematology <strong>and</strong><br />

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22. Fu S, Liesveld J. Mobilization of hematopoietic stem cells. Blood Rev. 2000;14(4):205-218.<br />

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25. Shea TC, DiPersio JF. Mobilization of autologous peripheral blood hematopoietic cells for cellular therapy. In: Applebaum FR,<br />

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26. Levesque JP, Winkler IG. Mobilization of hematopoietic stem cells: state of the art. Curr Opin Organ Transplant. 2008;13(1):53-58.<br />

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mobilization is superior to G-CSF alone. Blood. 2005;106(5):1867-1874.<br />

31. Cashen A, Lopez S, Gao F, et al. A phase II study of plerixafor (AMD3100) plus G-CSF for autologous hematopoietic progenitor cell<br />

mobilization in patients with Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008;14(11):1253-1261.<br />

32. Perez-Simon JA, Martin A, Caballero D, et al. Clinical significance of CD34+ cell dose in long-term engraftment following<br />

autologous peripheral blood stem cell transplantation. Bone Marrow Transplant. 1999;24(12):1279-1283.<br />

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 />

reduces febrile complications <strong>and</strong> use of antibiotics after transplantation. Bone Marrow Transplant. 1999;23(11):1177-1181.<br />

34. Montgomery M, Cottler-Fox M. Mobilization <strong>and</strong> collection of autologous hematopoietic progenitor/stem cells. Clin Adv Hematol<br />

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35. Pusic I, Jiang SY, L<strong>and</strong>ua S, et al. Impact of mobilization <strong>and</strong> remobilization strategies on achieving sufficient stem cell yields for<br />

autologous transplantation. Biol Blood Marrow Transplant. 2008;14(9):1045-1056.<br />

36. Giralt S, Stadtmauer EA, Harousseau JL, et al. International myeloma working group (IMWG) consensus statement <strong>and</strong><br />

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plerixafor (AMD 3100) Leukemia. 2009;Jun 25 [epub ahead of print].<br />

37. Jansen J, Thompson JM, Dugan MJ, et al. Peripheral blood progenitor cell transplantation. Ther Apher. 2002;6(1):5-14.<br />

38. Jansen J, Hanks S, Thompson JM, Dugan MJ, Akard LP. Transplantation of hematopoietic stem cells from the peripheral blood.<br />

J <strong>Cell</strong> Mol Med. 2005;9(1):37-50.<br />

39. Switzer GE, Goycoolea JM, Dew MA, Graeff EC, Hegl<strong>and</strong> J. Donating stimulated peripheral blood stem cells vs bone marrow: do<br />

donors experience the procedures differently? Bone Marrow Transplant. 2001;27(9):917-923.<br />

40. Damiani D, Fanin R, Silvestri F, et al. R<strong>and</strong>omized trial of autologous filgrastim-primed bone marrow transplantation versus<br />

filgrastim-mobilized peripheral blood stem cell transplantation in lymphoma patients. Blood. 1997;90(1):36-42.<br />

41. Bishop MR, Anderson JR, Jackson JD, et al. High-dose therapy <strong>and</strong> peripheral blood progenitor cell transplantation: effects of<br />

recombinant human granulocyte-macrophage colony-stimulating factor on the autograft. Blood. 1994;83(2):610-616.<br />

42. Kopf B, De Giorgi U, Vertogen B, et al. A r<strong>and</strong>omized study comparing filgrastim versus lenograstim versus molgramostim plus<br />

chemotherapy for peripheral blood progenitor cell mobilization. Bone Marrow Transplant. 2006;38(6):407-412.<br />

43. Petit I, Szyper-Kravitz M, Nagler A, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 <strong>and</strong> upregulating<br />

CXCR4. Nat Immunol. 2002;3(7):687-694.<br />

44. Levesque JP, Hendy J, Takamatsu Y, Williams B, Winkler IG, Simmons PJ. Mobilization by either cyclophosphamide or granulocyte<br />

colony-stimulating factor transforms the bone marrow into a highly proteolytic environment. Exp Hematol. 2002;30(5):440-449.<br />

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 />

mediated release of kit-lig<strong>and</strong>. <strong>Cell</strong>. 2002;109(5):625-637.<br />

46. Levesque JP, Takamatsu Y, Nilsson SK, Haylock DN, Simmons PJ. Vascular cell adhesion molecule-1 (CD106) is cleaved by<br />

neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating<br />

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 />

applicable national summary of product characteristics.<br />

48. Granocyte ® (lenograstim) [summary of product characteristics]. London, United Kingdom: Chugai Pharma UK Ltd; 2009. Please<br />

refer to the applicable national summary of product characteristics.<br />

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 />

colony-stimulating factor (filgrastim) for stem cell mobilization in healthy donors for allogeneic transplantation. Br J Haematol.<br />

2000;111(3):761-765.<br />

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 />

peripheral blood progenitor cells following chemotherapy in patients with multiple myeloma or non-Hodgkin’s lymphoma. Ann<br />

Hematol. 2005;84(11):742-747.<br />

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 />

non-Hodgkin’s lymphoma. Biol Blood Marrow Transplant. 2000;6(6):628-632.<br />

53. Naparstek E. The role of the anti-CD20 antibody rituximab in hematopoietic stem cell transplantation for non-Hodgkin’s<br />

lymphoma. Curr Hematol Rep. 2005;4(4):276-283.<br />

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 />

References<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.

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