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Haematopoietic Stem Cell
Mobilisation and Apheresis

A Practical Guide for
Nurses and Other Allied
Health Care Professionals

Module One: Scientific Background
and the Mobilisation Process
User Guidance
This document is the first module of a comprehensive guide to autologous stem
cell transplantation featuring details on the process; the agents used; potential
adverse events; scientific background. In module 2 information is given of the
practical recommendations and considerations for patients in your care.

It is recommended that the document is viewed in ‘presentation’ mode to ease
navigation through the document. On some occasions there is supplementary
information in the slide notes section.

Navigation explained:
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Hyperlinks are also embedded throughout the document
Autologous Haematopoietic Stem Cell
Transplantation
• Autologous haematopoietic stem cell transplantation (AHSCT)
  is a complex medical procedure that can be used to treat and
  cure patients with various malignant and non-malignant
  disorders

• “Autologous” means that the donor cells used for the
  procedure are from the patient themselves, as opposed to
  “allogeneic,” which refers to a cell donor other than the
  patient

• Historically, this treatment was offered only at large academic
  medical centres. However, due to medical progress and our
  knowledge of the AHSCT procedure, patients are receiving
  this therapy in community settings
                                                            S
Scientific Background on
Blood Cell Formation and
the Bone Marrow
Microenvironment




                           S
Blood Cell Formation - Haematopoiesis
Bone Marrow Microenvironment
• Haematopoiesis refers to the production of cellular components of blood
• This process occurs continually to maintain normal immune system function
  and haemostasis
• In adults, haematopoiesis primarily occurs in the bone marrow that is
  contained within the pelvis, sternum, vertebral column, and skull
• Production of mature blood cells specifically occurs in the bone marrow
  microenvironment




         S
Blood Cell Formation – Haematopoiesis 2

Stem Cell Maturation Cascade
• All blood cells are derived from
   progenitor stem cells, also
   referred to as pluripotent stem
   cells. These cells have the capacity
   for unlimited self-renewal and the
   ability to differentiate into all
   types of mature blood cells
• The pluripotent stem cell can
   differentiate into 1 of 2 types of
   common progenitor cells – the
   common myeloid progenitor and
   the common lymphoid progenitor


        S
The Bone Marrow Microenvironment
• Chemokines are a subset of cytokines associated with a single
  receptor and assist in cell movement
• Stromal cells are layers of cells that support the bone marrow
  microenvironment
• These cells produce the chemokine stem cell derived factor-1
  alpha (SDF-1a)
• This chemokine is an important signalling molecule involved in
  the proliferation, homing, and engraftment of stem cells
• For a given time in their development, stem cells express the
  chemokine receptor CXCR4. CXCR4 is responsible for anchoring
  stem cells to the bone marrow microenvironment


                                                           S
The Bone Marrow Microenvironment 2

• When CXCR4 and SDF-1a bind, interactions between
  integrin and cell adhesion molecules also occur
• The anchoring of stem cells within the bone marrow
  microenvironment occurs by continuous production of
  SDF-1a by stromal cells
• It is the loss of attachment to the stromal cells, along
  with the loss of SDF-1a activity, that favours the release
  of stem cells into peripheral circulation
• Blockade of this receptor with a chemokine antagonist
  (such as plerixafor) has elevated circulating
  haematopoietic stem cells (HSCs) and aided stem cell
  collections in patients with multiple myeloma and
  lymphoma

                                                         S
The Stem Cell Transplant
Process




                           S
Stem cells and CD34
• Pluripotent stem cells express the cell surface marker antigen CD34
• This marker is the indicator most frequently used in clinical practice to
  determine the extent and efficiency of peripheral blood stem cell
  collections
• Although not a complete measure of the quantity and quality of collected
  cells, blood samples from collections are assayed to determine the
  number of CD34+ cells present
• Once specific cell targets are achieved, cell collections are completed and
  stored for future use
• Standard target levels can vary among treatment centres and a patient’s
  specific goal is related to the underlying disease, the source of stem
  cells, and the type of transplantation to be performed
• In general, a target level of 2 × 106 cells/kg is desired
• A comprehensive list of AHSCT indications in Adults can be found here

                                                                        S
The Stem Cell Transplant Process
    Injection of mobilising agents       Mobilisation                 Collection
1                                    2                            3




    Preparation & storage                Cryopreservation
4                                    5                            6 Chemo / radiotherapy




     Stem cell transplant                Engraftment & recovery
7                                    8




                                                                                   S
A Short Film on the Stem Cell Transplant Process
is Included Below




   S
Mobilisation

• Filgrastim and lenograstim used as single-agent mobilisers are well established, with both
  agents having reliably demonstrated increased concentrations of circulating HSCs
• G-CSF is thought to stimulate HSC mobilisation by decreasing SDF-1a gene expression and
  protein levels while increasing proteases that can cleave interactions between HSCs and
  the bone marrow environment
• Data indicate that divided doses of G-CSF (e.g. lenograstim 5 mcg/kg twice daily) are
  more efficacious than single-dose administration (e.g. lenograstim 10 mcg/kg once daily)
  by producing a higher yield of CD34+ cells and the need for fewer apheresis procedures
• However, current clinical practice does not favour one schedule over the other
• Since it is common to see an increase in                                  Mechanism of Action of G-CSF
  HSCs following recovery from
  myelosuppressive chemotherapy, another
  method to mobilise HSCs involves the
  administration of chemotherapy, usually in
  conjunction with cytokines. This is
  frequently referred to as “chemo-
  mobilisation”



            S
Mobilisation
• Chemotherapy and cytokines work synergistically to mobilise HSCs, although the exact
  mechanism for chemotherapy mobilisation is not fully understood
• Possible mechanisms for mobilisation following chemotherapy include chemotherapy effects
  on the expression of cell adhesion molecules in the bone marrow and chemotherapy-
  induced damage to stromal cells in the bone marrow
• Both of these lead to increased circulating concentrations of HSCs due to disruption of the
  bone marrow microenvironment
• Chemotherapeutic agents most
  commonly used for chemomobilisation
  include high-dose cyclophosphamide
  and etoposide
• Filgrastim (5 mcg/kg/day) can be
  utilised as the cytokine partner in
  chemomobilisation
• Because no single chemotherapy
  mobilisation regimen has demonstrated
  superiority over the others, some
  clinicians may elect to mobilise patients
  during a cycle of a disease directed
  chemotherapy regimen
                                                 Generalised Kinetics of Leucocyte and CD34+ Cell
         S                                       Mobilisation Into the Peripheral Blood Following
                                                   Chemotherapy and Cytokine Administration
Mobilisation with Chemotherapy
•    Examples of regimens utilised include CHOP
     (cyclophosphamide, doxorubicin, vincristine, and prednisone) and ICE
     (ifosfamide, carboplatin, and etoposide)
•    Additionally, the use of rituximab (a monoclonal antibody directed at cells that express
     CD20) prior to mobilisation has not demonstrated inferior yields of CD34+ cells; in fact, it
     may assist with decreasing the amount of tumour contamination in the collected product
•    The complications with chemotherapies commonly used for mobilisation are included in
     the table below
Short term side effects                                                         Long term side effects

• General malaise (weakness)                                                    • Decreased urination (may be a
• Infertility                                                                     sign of kidney damage)
• GI symptoms (diarrhoea, nausea, vomiting, appetite loss, stomach              • Difficulty breathing or water
  discomfort or pain)                                                             retention (which may be a sign
• Skin & mucosal effects (rash, texture change in nails, alopecia, mucositis)     of congestive heart failure)
• Myelosuppression (thrombocytopenia, leucopenia)                               • Secondary malignancies (may
• Infusion-related side effects (hypotension, flushing, chest pain, fever,        present as unusual moles, skin
  diaphoresis, cyanosis, urticaria, angio-oedema, bronchospasm)                   sores that do not heal or
• Allergic reaction                                                               unusual lumps)
• Signs of infection, such as chills or a fever
• Blood in the urine (may be a sign of bladder damage)
• Blood in stool


                                                                                                         S
Mobilisation with Plerixafor and other Agents
•     Plerixafor is a novel agent that has recently been
      approved in the European Union for use in conjunction
      with G-CSF in lymphoma and multiple myeloma patients
      whose cells mobilise poorly, to mobilise stem cells from
      the bone marrow into the peripheral blood for collection
      and autologous transplantation
•     Plerixafor is a small-molecule CXCR4 antagonist that
      reversibly inhibits the interaction between CXCR4 and
      SDF-1a
•     Use of plerixafor in combination with G-CSF has been
      shown to improve CD34+ cell collections in lymphoma
      and multiple myeloma patients compared to G-CSF alone

    Agent          Adverse events                                    Very Common (> 10%)
                                                                     Adverse Reactions
    Filgrastim     • Musculoskeletal pain                            Associated With Agents
    Lenograstim    •   Bone & back pain                              Used in Stem Cell
                   •   Leucocytosis & thrombocytopenia               Mobilisation
                   •   Transient increases in liver function tests
                   •   Elevated LDH
                   •   Headache & asthenia (weakness)
    Plerixafor     • Diarrhoea & nausea
                   • Injection & infusion site reactions                           S
A Short Film on the Plerixafor Mode of Action is
Included Below




   S
Comparison of Mobilisation Methods
Mobilisation regimen          Characteristics

Filgrastim or lenograstim     •   Low toxicity
                              •   Outpatient administration
                              •   Can be self-administered
                              •   Reasonable efficacy in most patients
                              •   Predictable mobilisation, permitting easy apheresis scheduling
                              •   Shorter time from administration to collection compared to growth factor + chemotherapy
                              •   Bone pain
                              •   Lower stem cell yield compared to growth factor + chemotherapy
Filgrastim or lenograstim +   •   Higher stem cell yield compared to growth factor alone
chemotherapy                  •   Fewer stem cell collections
                              •   Potential for anticancer activity
                              •   May impair future mobilisation of stem cells
                              •   May require hospitalisation
                              •   Associated with increased numbers of side effects
                              •   Inconsistent results
                              •   Longer time from administration to collection compared to growth factor
                              •   Low predictability of time to peak peripheral blood CD34+ cell levels
Filgrastim or lenograstim +   •   Low toxicity
plerixafor                    •   Outpatient administration
                              •   Low failure rate
                              •   High probability of collecting optimal number of CD34+ cells
                              •   Efficacy in poor mobilisers
                              •   Predictable mobilisation permitting easy apheresis scheduling
                              •   Shorter time from administration to collection compared to growth factor + chemotherapy
                              •   Gastrointestinal adverse affects

                                                                                                                     S
Risk Factors and Characteristics Associated with
Poor Autologous Stem Cell Mobilisation
• Type and amount of chemotherapy administered to patient prior to
  mobilisation
• Advanced age (> 60 years)
• Multiple cycles of previous chemotherapy for treatment of
  underlying disease
• Radiation therapy
• Short time interval between chemotherapy and mobilisation
• Extensive disease burden
• Refractory disease
• Tumour infiltration of bone marrow
• Prior use of lenalidomide
• Evidence of poor marrow function (e.g. low platelet and CD34+
  blood count) at time of mobilisation


                                                             S
Autologous Stem Cell Collection
•   Historically, autologous stem cell
    collections involved the removal of
    bone marrow cells from a patient’s
    bilateral posterior iliac crest region
    under general anaesthesia in a
    hospital operating room




•   However, due to advances in
    medical technology, most collections
    today are performed by apheresis
•   Peripheral blood stem cell collection
    is considered the preferred method
    for mobilisation prior to AHSCT due
    to patient convenience, decreased
    morbidity, and faster engraftment of
    WBCs and platelets
                                             S
Advantages and Disadvantages of
Haematopoietic Stem Cell Collection Methods
Collection    Advantages                                     Disadvantages
method

Bone marrow   • Single collection                            • Performed in an acute care setting since it
              • No need for special catheter placement         requires general anaesthesia
              • Use of cytokines not necessary               • Slower neutrophil and platelet engraftment
                                                             • Higher rates of morbidity and mortality
                                                             • Potentially more tumour cell contamination
                                                               of product


Peripheral    • Does not require general anaesthesia and     • Collection may take several days
blood           can be performed in an outpatient setting    • Sometimes requires placement of large-bore,
              • Faster neutrophil and platelet engraftment     double-lumen catheter for collection
              • Associated with lower rates of morbidity     • Haemorrhage, embolism and infection are
                and mortality                                  possible complications related to insertion of
              • Potentially less tumour cell contamination     central venous catheter
                of product




                                                                                                   S
Stem Cell Collection (Apheresis): Patient
Evaluation 1
• Prior to initiation of the stem cell collection process, patients must be
  thoroughly evaluated and determined to be acceptable transplant
  candidates and able to tolerate all of the procedures involved
   – Some of the medical, nursing, and psychosocial evaluations can occur
      prior to a patient’s first visit or referral to a transplant service or clinic

    – The patient’s primary medical haematologist/oncologist frequently
      serves as a patient’s first contact during the transplantation process

    – All of the testing, evaluation, and education involved throughout a
      patient’s transplant involves a myriad of health care professionals
      working together to orchestrate this complex medical procedure




                                                                                S
Stem Cell Collection (Apheresis): Patient
Evaluation 2

• The medical pre-evaluation is the first step a patient must complete when
  undergoing an AHSCT
   – This involves the patient’s primary medical oncologist making a
     referral to a transplant centre or service
   – The physician provides the transplant team with information that
     often includes specifics relating to the care of the patient up to this
     time point, such as past medical history, cancer status, summary of
     cancer treatments and responses, and complications experienced
     during therapy
   – Accompanying this information are any available radiograph and
     laboratory testing results




                                                                      S
Stem Cell Collection (Apheresis): Preparation 1

•    Upon determination that a patient is eligible to proceed to transplantation,
     preparing them for the collection process occurs next
•    The preferred method for venous access is the placement of a peripheral catheter at
     the time of an apheresis session (e.g. insertion into the antecubital vein)
•    For those patients in whom peripheral line placement is not feasible, appropriate
     catheter selection and central venous placement (e.g. internal jugular or femoral
     vein) is scheduled prior to the first stem cell collection
•    Catheters used for apheresis procedures must be able to tolerate large fluctuations
     in circulating blood volume
•    Therefore, these catheters are often large-bore, double lumen devices that can be
     used temporarily during cell collections, or placed permanently and used
     throughout the transplantation process. As with most catheters placed in the area of
     the upper extremities, patients should be monitored for signs and symptoms of
     hypotension, shortness of breath, and decreased breath sounds as these can be
     indicative of venous wall perforation, haemothorax, and/or pneumothorax, all of
     which are rare but serious complications that can occur


                                                                                  S
Stem Cell Collection (Apheresis): Preparation 2


• Preparation for stem cell collections in an apheresis centre or unit follows
  the pre-transplantation evaluation and catheter placement
• Patients will be advised and counselled on therapies that they will receive
  during mobilisation with respect to administration schedule and expected
  adverse effects
• Agents used during this stage of AHSCT usually include single-agent
  cytokines (such as filgrastim) that are given with or without certain
  chemotherapy agents, a designated cycle of disease-specific
  chemotherapy regimen, or more recently, filgrastim or lenograstim in
  combination with plerixafor
• Upon initiation of the mobilisation regimen, patients can expect to
  undergo their first apheresis session in as little as 4 to 5 days or, in some
  cases, 2 to 3 weeks later


                                                                         S
Stem Cell Collection (Apheresis): Mobilisation 1

• The extent of mobilisation is determined through the patient’s WBC count.
  Serial measurements of the patient’s WBC count will assist the clinician in
  determining the appropriate time to commence collection procedures
• Additionally, centres may use peripheral blood CD34+ cell levels as a
  surrogate for mobilisation status
• Established thresholds for apheresis initiation may vary across centres, but
  typically range from 5 to 20 CD34+ cells/micro-litre
• Although useful in estimating mobilisation efficacy, peripheral blood
  CD34+ counts can be variable within and across centres
• Once mobilisation has reached an optimal level, a patient can be
  scheduled for sessions in the apheresis centre




                                                                        S
Stem Cell Collection (Apheresis): Mobilisation 2

• An apheresis technician highly trained in stem cell collections is
  responsible for the equipment utilised in the collection process
• Clinical nurses working in the apheresis unit are responsible for
  educating the patient about the stem cell collection process and
  monitoring patients for any adverse reactions. Patients are connected
  to the apheresis machine by their catheter
• One lumen is used to draw blood out of the patient and into the
  machine
• Here the blood is spun at high speeds in a centrifugation chamber
  housed within the cell separator machine
• The desired stem cells are collected during the entire procedure, either
  in cycles or continuously, and the remaining blood components are
  returned to the patient through the second lumen of their catheter
• This second lumen can additionally be used to administer intravenous
  fluids, electrolyte supplements, and medications to the patient

                                                                    S
SEPARATORE CELLULARE
                            Examples of apheresis machines




.


    Cell separator: The cell separators used are the COMTEC Fresenius and COBE Spectra. Their
    function is to spin the blood in order to allow separation and collection of individual cellular
    components. The cell separators provide circuits and strictly sterile and disposable materials.
                                                                                                 S
COBE SPECTRA SPIN                                                                  COMTEC FRESENIUS SPIN



Apheresis procedures are relatively safe. Although the mortality rate is quite low at an estimated 3
deaths per 10,000 procedures, apheresis is associated with some morbidity. Citrate is an
anticoagulant used during the apheresis process to prevent blood clotting. Thus, one of the most
common adverse effects seen during this procedure is citrate toxicity manifested as hypocalcaemia.
This occurs due to binding of ionised serum calcium, which leads to hypocalcaemia. Signs and
symptoms of citrate toxicity as well as its management are further described in the next table.
Monitoring serum calcium levels prior to and throughout apheresis may decrease the likelihood of
hypocalcaemia.

Additional adverse effects of citrate toxicity include hypomagnesaemia, hypokalaemia, and metabolic
alkalosis. The magnesium ion, like the calcium ion, is divalent and is bound by citrate. Declines in
serum magnesium levels are often more pronounced and take longer to normalise compared to
aberrations in calcium levels. Signs and symptoms of hypomagnesaemia, hypokalaemia, and
metabolic alkalosis as well as their management are further described in the next table.
                                                                                                S
Common Apheresis Complications
Adverse event      Cause                           Signs & symptoms                                           Corrective action

Citrate toxicity   Anticoagulant (citrate) given   Hypocalcaemia                                              Slow the rate of apheresis; increase
                   during apheresis                Common: dizziness & tingling in mouth area, hands          the blood:citrate ratio; calcium
                                                   & feet                                                     replacement therapy
                                                   Uncommon: chills, tremors, muscle twitching &
                                                   cramps, abdominal cramps, tetany, seizure, cardiac
                                                   arrhythmia
                                                   Hypomagnesaemia                                            Slow the rate of apheresis; increase
                                                   Common: muscle spasm or weakness                           the blood:citrate ratio; magnesium
                                                   Uncommon: hypotonia & cardiac arrhythmia                   replacement therapy
                                                   Hypokalaemia                                               Slow the rate of apheresis; increase
                                                   Common: weakness                                           the blood:citrate ratio; potassium
                                                   Uncommon: decrease in respiration rate                     replacement therapy
                                                   Metabolic alkalosis                                        Slow the rate of apheresis; increase
                                                   Common: worsening of hypocalcaemia                         the blood:citrate ratio
                                                   Uncommon: decrease in respiration rate
Thrombocytopenia   Platelets adhere to internal    Low platelet count, bruising, bleeding                     Slow the rate of apheresis; increase
                   surface of the apheresis                                                                   the blood:citrate ratio
                   machine
Hypovolaemia       Patient intolerant of large     Dizziness, fatigue, light-headedness, tachycardia,         Slow rate of apheresis session or
                   shift in extracorporeal blood   hypotension, diaphoresis, cardiac arrhythmia               temporarily stop it; intravenous
                   and plasma volumes                                                                         fluid boluses
Catheter           Blood clot forms of catheter    Inability to flush catheter, fluid collection under skin   Reposition the catheter; gently
malfunction        is not well positioned to       around catheter site, pain & erythema at catheter          flush catheter; treat blood clot
                   allow for adequate blood        site; arm swelling, decrease in blood flow
                   flow
Infection          Microbial pathogens enter       Fever, chills, fatigue, red & erythematous skin            Administer antibiotics; possibly
                   bloodstream through             around catheter; hypotension, position blood               remove catheter
                   catheter or catheter site       cultures

                                                                                                                                    S
Apheresis Complications: Hypovolaemia

•   Due to large fluctuations in blood volume during apheresis, patients may
    experience hypovolaemia
•   Prior to starting apheresis, baseline pulse and blood pressure are measured and
    continuously assessed at regular intervals. It is recommended that haemoglobin
    and haematocrit are also monitored
•   Patients at risk of developing hypovolaemia include those with anaemia, those
    with a previous history of cardiovascular compromise, and children or adults with
    a small frame
•   Preventative measures are aimed at minimising the extracorporeal volume shift by
    priming the apheresis machine with red blood cells and fresh frozen plasma in
    place of normal saline
•   Hypovolaemia may also be managed by providing intravenous fluid boluses and
    slowing the rate of flow on the apheresis machine
•   Another potential problem stemming from hypovolaemia is the development of a
    life-threatening cardiac dysrhythmia. If this occurs, apheresis should be
    interrupted and symptoms should subside before proceeding with collections

                                                                              S
Cryopreservation
•   Many centres have cryopreservation laboratories that maintain collected stem                   cell
    products in liquid nitrogen until the time of the patient’s transplantation
•   Human cells can be cryopreserved in liquid nitrogen for several years without significant changes of their
    biological characteristics



•   A common cryopreservative used is dimethylsulfoxide (DMSO) which maintains cell viability by preventing
    ice crystal formation within the cells during storage
•   The collected product may be manipulated by a pharmacological, immunological, or physical method to
    reduce contamination with tumour cells. Quality testing is performed on collections to ascertain
    contamination with microbes as well as to determine the number of viable cells available for
    transplantation



•   Once a patient reaches their CD34+ collection goal, apheresis sessions are complete
•   Reaching minimum thresholds for CD34+ cell amounts is important as cell dose appears to positively
    correlate with engraftment and outcome
•   The total number of stem cells for the reinfusion may vary depending on the disease and the conditioning
    regimen used for the patient



•   The count of harvested stem cells determines if the patient has reached the target sufficient to support HD
    chemotherapy conditioning and cell transplantation
                                                                                                       S
High-dose Chemotherapy
(Conditioning Regimen)
• To perform the transplant, the patient will undergo a hospitalisation
  period of 3-4 weeks in a protected environment
• During this period, high-dose chemotherapy or radiotherapy will be
  performed as a conditioning regimen. The central venous access will be
  placed, generally in the subclavian vein, catheter or Port-a-Cath
• Approximately 1 week prior to the transplant date, patients begin their
  preparative regimen in the ambulatory or inpatient unit of the hospital
    – This may consist of chemotherapy alone or chemotherapy in combination with
      radiation therapy
    – Chemotherapy agents selected for use during this time may differ from those
      used during previous cancer treatments or during mobilisation
    – The patient often benefits from cyto-reduction in their tumour following this
      phase of treatment
    – Due to the intensity of treatment, patients can experience ablation of their
      bone marrow stores and therefore need infusion of their previously collected
      cells as “rescue” therapy                                                S
Common Side Effects of Chemotherapy

• The disorders most frequently associated with the
  administration of chemotherapy regimens in the
  conditioning phase depend on the scheme used and
  include:
   – Reduction of white blood cells with the potential risk of
     infection (Neutropenia)
   – Fever
   – Possible need for red blood cell transfusion and/or platelets
     (Anaemia)
   – Nausea/vomiting
   – Painful inflammation and ulceration of the mucous membranes
     lining the digestive tract (Mucositis)
   – Hair loss (Alopecia)


                                                             S
Detailed Side Effects of AHSCT Chemotherapy
by Organ
Organ               Side Effect                       Intervention
Gastrointestinal    Nausea, vomiting, diarrhoea,      Antiemetic drugs, mouth care regimens, pain
tract               weight loss, mucositis            medication, nutritional supplementations
Blood               Pancytopenia*                     Antibiotics, blood transfusions
Kidneys             Haemorrhagic cystitis*            Mesna, intravenous fluids, pain medications,
                                                      bladder irrigation
Liver               Sinusoidal obstructive syndrome   Diuretics, fluid restriction, intensive supportive
                    (veno-occlusive disease)*         care
Brain / CNS         Headache, tremors, seizures       Pain medication, intensive supportive care
Heart               Oedema, hypertension              Fluid restriction, diuretics, antihypertensive
                                                      medication
Lungs               Atelectasis*                      Pulmonary hygiene (formerly known as
                                                      pulmonary toilet)
Skin                Rash, discolouration              Topical emollients, skin care, and bathing
                                                      regimens



*See notes for detailed descriptions                                                          S
Stem Cell Transplant

• Before high-dose chemotherapy is administered to the patient, the integrity of
  stored stem cells is verified
• On the day of stem cell infusion, the previously collected product is removed
  from liquid nitrogen storage, thawed, and prepared for patient administration
• The infusion itself can occur in an ambulatory or hospital setting. Prior to
  infusion, the product is rigorously inspected and tested for quality control
  measures, such as CD34+ cell counts and the presence of microbes
• Several members of the health care team will also ensure that the product is
  the patient’s collected cells
• The patient is prepared for the infusion by receiving pre-medications (e.g. an
  antihistamine, an antipyretic), having their intravenous line equipped to
  receive the cells, and being placed on medical equipment to monitor their vital
  signs throughout the procedure


                                                                        S
Complications Associated With Autologous Stem
Cell Infusion
Adverse Event                Signs & symptoms                                    Corrective action

Reactions to DMSO            Common:                                             Treatment of symptoms
                             • Nausea
                             • Vomiting
                             • Abdominal cramping
                             • Headache
                             • Garlic aftertaste
                             Rare:
                             • Hypotension
                             • Rapid heart rate
                             • Shortness of breath
                             • Fever
                             • Neurological complications
Oedema                       •   Fluid retention                                 Diuretics, fluid restriction
                             •   Puffiness
                             •   Weight gain
                             •   Hypertension
Contamination of stem cell   •   Hypotension                                     Antibiotics, intensive
product                      •   Rapid heart rate                                supportive care
                             •   Shortness of breath
                             •   Fever
                             •   Chills
                             •   Rigors
                             •   Positive blood culture for microbial pathogen

                                                                                                                S
Engraftment & Recovery

• During this critical time, the infused stem cells find their way
  back to the bone marrow microenvironment and repopulate
  depleted marrow stores
• Post-transplant, cytokines are administered to enhance stem
  cell maturation and to re-establish blood cell components
• The first sign of engraftment is the return of circulating WBCs
  to a sufficient level defined as an absolute neutrophil count
  (ANC) of > 500/mm for 3 consecutive days, which typically
  occurs 7-14 days after the stem cells have been infused into
  the patient
• Increased platelet levels (absent of transfusion support) is
  another indicator of recovery, occurring at a later time
  point, averaging 2-3 weeks following the transplant


                                                             S
For information on the indications for
transplant and the nurse’s role please see
module two

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Guide to Autologous Stem Cell Transplantation

  • 1. Haematopoietic Stem Cell Mobilisation and Apheresis A Practical Guide for Nurses and Other Allied Health Care Professionals Module One: Scientific Background and the Mobilisation Process
  • 2. User Guidance This document is the first module of a comprehensive guide to autologous stem cell transplantation featuring details on the process; the agents used; potential adverse events; scientific background. In module 2 information is given of the practical recommendations and considerations for patients in your care. It is recommended that the document is viewed in ‘presentation’ mode to ease navigation through the document. On some occasions there is supplementary information in the slide notes section. Navigation explained: Return to the home slide Return to stem cell transplant landing page S Next slide Previous slide Go to last slide viewed Hyperlinks are also embedded throughout the document
  • 3. Autologous Haematopoietic Stem Cell Transplantation • Autologous haematopoietic stem cell transplantation (AHSCT) is a complex medical procedure that can be used to treat and cure patients with various malignant and non-malignant disorders • “Autologous” means that the donor cells used for the procedure are from the patient themselves, as opposed to “allogeneic,” which refers to a cell donor other than the patient • Historically, this treatment was offered only at large academic medical centres. However, due to medical progress and our knowledge of the AHSCT procedure, patients are receiving this therapy in community settings S
  • 4. Scientific Background on Blood Cell Formation and the Bone Marrow Microenvironment S
  • 5. Blood Cell Formation - Haematopoiesis Bone Marrow Microenvironment • Haematopoiesis refers to the production of cellular components of blood • This process occurs continually to maintain normal immune system function and haemostasis • In adults, haematopoiesis primarily occurs in the bone marrow that is contained within the pelvis, sternum, vertebral column, and skull • Production of mature blood cells specifically occurs in the bone marrow microenvironment S
  • 6. Blood Cell Formation – Haematopoiesis 2 Stem Cell Maturation Cascade • All blood cells are derived from progenitor stem cells, also referred to as pluripotent stem cells. These cells have the capacity for unlimited self-renewal and the ability to differentiate into all types of mature blood cells • The pluripotent stem cell can differentiate into 1 of 2 types of common progenitor cells – the common myeloid progenitor and the common lymphoid progenitor S
  • 7. The Bone Marrow Microenvironment • Chemokines are a subset of cytokines associated with a single receptor and assist in cell movement • Stromal cells are layers of cells that support the bone marrow microenvironment • These cells produce the chemokine stem cell derived factor-1 alpha (SDF-1a) • This chemokine is an important signalling molecule involved in the proliferation, homing, and engraftment of stem cells • For a given time in their development, stem cells express the chemokine receptor CXCR4. CXCR4 is responsible for anchoring stem cells to the bone marrow microenvironment S
  • 8. The Bone Marrow Microenvironment 2 • When CXCR4 and SDF-1a bind, interactions between integrin and cell adhesion molecules also occur • The anchoring of stem cells within the bone marrow microenvironment occurs by continuous production of SDF-1a by stromal cells • It is the loss of attachment to the stromal cells, along with the loss of SDF-1a activity, that favours the release of stem cells into peripheral circulation • Blockade of this receptor with a chemokine antagonist (such as plerixafor) has elevated circulating haematopoietic stem cells (HSCs) and aided stem cell collections in patients with multiple myeloma and lymphoma S
  • 9. The Stem Cell Transplant Process S
  • 10. Stem cells and CD34 • Pluripotent stem cells express the cell surface marker antigen CD34 • This marker is the indicator most frequently used in clinical practice to determine the extent and efficiency of peripheral blood stem cell collections • Although not a complete measure of the quantity and quality of collected cells, blood samples from collections are assayed to determine the number of CD34+ cells present • Once specific cell targets are achieved, cell collections are completed and stored for future use • Standard target levels can vary among treatment centres and a patient’s specific goal is related to the underlying disease, the source of stem cells, and the type of transplantation to be performed • In general, a target level of 2 × 106 cells/kg is desired • A comprehensive list of AHSCT indications in Adults can be found here S
  • 11. The Stem Cell Transplant Process Injection of mobilising agents Mobilisation Collection 1 2 3 Preparation & storage Cryopreservation 4 5 6 Chemo / radiotherapy Stem cell transplant Engraftment & recovery 7 8 S
  • 12. A Short Film on the Stem Cell Transplant Process is Included Below S
  • 13. Mobilisation • Filgrastim and lenograstim used as single-agent mobilisers are well established, with both agents having reliably demonstrated increased concentrations of circulating HSCs • G-CSF is thought to stimulate HSC mobilisation by decreasing SDF-1a gene expression and protein levels while increasing proteases that can cleave interactions between HSCs and the bone marrow environment • Data indicate that divided doses of G-CSF (e.g. lenograstim 5 mcg/kg twice daily) are more efficacious than single-dose administration (e.g. lenograstim 10 mcg/kg once daily) by producing a higher yield of CD34+ cells and the need for fewer apheresis procedures • However, current clinical practice does not favour one schedule over the other • Since it is common to see an increase in Mechanism of Action of G-CSF HSCs following recovery from myelosuppressive chemotherapy, another method to mobilise HSCs involves the administration of chemotherapy, usually in conjunction with cytokines. This is frequently referred to as “chemo- mobilisation” S
  • 14. Mobilisation • Chemotherapy and cytokines work synergistically to mobilise HSCs, although the exact mechanism for chemotherapy mobilisation is not fully understood • Possible mechanisms for mobilisation following chemotherapy include chemotherapy effects on the expression of cell adhesion molecules in the bone marrow and chemotherapy- induced damage to stromal cells in the bone marrow • Both of these lead to increased circulating concentrations of HSCs due to disruption of the bone marrow microenvironment • Chemotherapeutic agents most commonly used for chemomobilisation include high-dose cyclophosphamide and etoposide • Filgrastim (5 mcg/kg/day) can be utilised as the cytokine partner in chemomobilisation • Because no single chemotherapy mobilisation regimen has demonstrated superiority over the others, some clinicians may elect to mobilise patients during a cycle of a disease directed chemotherapy regimen Generalised Kinetics of Leucocyte and CD34+ Cell S Mobilisation Into the Peripheral Blood Following Chemotherapy and Cytokine Administration
  • 15. Mobilisation with Chemotherapy • Examples of regimens utilised include CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and ICE (ifosfamide, carboplatin, and etoposide) • Additionally, the use of rituximab (a monoclonal antibody directed at cells that express CD20) prior to mobilisation has not demonstrated inferior yields of CD34+ cells; in fact, it may assist with decreasing the amount of tumour contamination in the collected product • The complications with chemotherapies commonly used for mobilisation are included in the table below Short term side effects Long term side effects • General malaise (weakness) • Decreased urination (may be a • Infertility sign of kidney damage) • GI symptoms (diarrhoea, nausea, vomiting, appetite loss, stomach • Difficulty breathing or water discomfort or pain) retention (which may be a sign • Skin & mucosal effects (rash, texture change in nails, alopecia, mucositis) of congestive heart failure) • Myelosuppression (thrombocytopenia, leucopenia) • Secondary malignancies (may • Infusion-related side effects (hypotension, flushing, chest pain, fever, present as unusual moles, skin diaphoresis, cyanosis, urticaria, angio-oedema, bronchospasm) sores that do not heal or • Allergic reaction unusual lumps) • Signs of infection, such as chills or a fever • Blood in the urine (may be a sign of bladder damage) • Blood in stool S
  • 16. Mobilisation with Plerixafor and other Agents • Plerixafor is a novel agent that has recently been approved in the European Union for use in conjunction with G-CSF in lymphoma and multiple myeloma patients whose cells mobilise poorly, to mobilise stem cells from the bone marrow into the peripheral blood for collection and autologous transplantation • Plerixafor is a small-molecule CXCR4 antagonist that reversibly inhibits the interaction between CXCR4 and SDF-1a • Use of plerixafor in combination with G-CSF has been shown to improve CD34+ cell collections in lymphoma and multiple myeloma patients compared to G-CSF alone Agent Adverse events Very Common (> 10%) Adverse Reactions Filgrastim • Musculoskeletal pain Associated With Agents Lenograstim • Bone & back pain Used in Stem Cell • Leucocytosis & thrombocytopenia Mobilisation • Transient increases in liver function tests • Elevated LDH • Headache & asthenia (weakness) Plerixafor • Diarrhoea & nausea • Injection & infusion site reactions S
  • 17. A Short Film on the Plerixafor Mode of Action is Included Below S
  • 18. Comparison of Mobilisation Methods Mobilisation regimen Characteristics Filgrastim or lenograstim • Low toxicity • Outpatient administration • Can be self-administered • Reasonable efficacy in most patients • Predictable mobilisation, permitting easy apheresis scheduling • Shorter time from administration to collection compared to growth factor + chemotherapy • Bone pain • Lower stem cell yield compared to growth factor + chemotherapy Filgrastim or lenograstim + • Higher stem cell yield compared to growth factor alone chemotherapy • Fewer stem cell collections • Potential for anticancer activity • May impair future mobilisation of stem cells • May require hospitalisation • Associated with increased numbers of side effects • Inconsistent results • Longer time from administration to collection compared to growth factor • Low predictability of time to peak peripheral blood CD34+ cell levels Filgrastim or lenograstim + • Low toxicity plerixafor • Outpatient administration • Low failure rate • High probability of collecting optimal number of CD34+ cells • Efficacy in poor mobilisers • Predictable mobilisation permitting easy apheresis scheduling • Shorter time from administration to collection compared to growth factor + chemotherapy • Gastrointestinal adverse affects S
  • 19. Risk Factors and Characteristics Associated with Poor Autologous Stem Cell Mobilisation • Type and amount of chemotherapy administered to patient prior to mobilisation • Advanced age (> 60 years) • Multiple cycles of previous chemotherapy for treatment of underlying disease • Radiation therapy • Short time interval between chemotherapy and mobilisation • Extensive disease burden • Refractory disease • Tumour infiltration of bone marrow • Prior use of lenalidomide • Evidence of poor marrow function (e.g. low platelet and CD34+ blood count) at time of mobilisation S
  • 20. Autologous Stem Cell Collection • Historically, autologous stem cell collections involved the removal of bone marrow cells from a patient’s bilateral posterior iliac crest region under general anaesthesia in a hospital operating room • However, due to advances in medical technology, most collections today are performed by apheresis • Peripheral blood stem cell collection is considered the preferred method for mobilisation prior to AHSCT due to patient convenience, decreased morbidity, and faster engraftment of WBCs and platelets S
  • 21. Advantages and Disadvantages of Haematopoietic Stem Cell Collection Methods Collection Advantages Disadvantages method Bone marrow • Single collection • Performed in an acute care setting since it • No need for special catheter placement requires general anaesthesia • Use of cytokines not necessary • Slower neutrophil and platelet engraftment • Higher rates of morbidity and mortality • Potentially more tumour cell contamination of product Peripheral • Does not require general anaesthesia and • Collection may take several days blood can be performed in an outpatient setting • Sometimes requires placement of large-bore, • Faster neutrophil and platelet engraftment double-lumen catheter for collection • Associated with lower rates of morbidity • Haemorrhage, embolism and infection are and mortality possible complications related to insertion of • Potentially less tumour cell contamination central venous catheter of product S
  • 22. Stem Cell Collection (Apheresis): Patient Evaluation 1 • Prior to initiation of the stem cell collection process, patients must be thoroughly evaluated and determined to be acceptable transplant candidates and able to tolerate all of the procedures involved – Some of the medical, nursing, and psychosocial evaluations can occur prior to a patient’s first visit or referral to a transplant service or clinic – The patient’s primary medical haematologist/oncologist frequently serves as a patient’s first contact during the transplantation process – All of the testing, evaluation, and education involved throughout a patient’s transplant involves a myriad of health care professionals working together to orchestrate this complex medical procedure S
  • 23. Stem Cell Collection (Apheresis): Patient Evaluation 2 • The medical pre-evaluation is the first step a patient must complete when undergoing an AHSCT – This involves the patient’s primary medical oncologist making a referral to a transplant centre or service – The physician provides the transplant team with information that often includes specifics relating to the care of the patient up to this time point, such as past medical history, cancer status, summary of cancer treatments and responses, and complications experienced during therapy – Accompanying this information are any available radiograph and laboratory testing results S
  • 24. Stem Cell Collection (Apheresis): Preparation 1 • Upon determination that a patient is eligible to proceed to transplantation, preparing them for the collection process occurs next • The preferred method for venous access is the placement of a peripheral catheter at the time of an apheresis session (e.g. insertion into the antecubital vein) • For those patients in whom peripheral line placement is not feasible, appropriate catheter selection and central venous placement (e.g. internal jugular or femoral vein) is scheduled prior to the first stem cell collection • Catheters used for apheresis procedures must be able to tolerate large fluctuations in circulating blood volume • Therefore, these catheters are often large-bore, double lumen devices that can be used temporarily during cell collections, or placed permanently and used throughout the transplantation process. As with most catheters placed in the area of the upper extremities, patients should be monitored for signs and symptoms of hypotension, shortness of breath, and decreased breath sounds as these can be indicative of venous wall perforation, haemothorax, and/or pneumothorax, all of which are rare but serious complications that can occur S
  • 25. Stem Cell Collection (Apheresis): Preparation 2 • Preparation for stem cell collections in an apheresis centre or unit follows the pre-transplantation evaluation and catheter placement • Patients will be advised and counselled on therapies that they will receive during mobilisation with respect to administration schedule and expected adverse effects • Agents used during this stage of AHSCT usually include single-agent cytokines (such as filgrastim) that are given with or without certain chemotherapy agents, a designated cycle of disease-specific chemotherapy regimen, or more recently, filgrastim or lenograstim in combination with plerixafor • Upon initiation of the mobilisation regimen, patients can expect to undergo their first apheresis session in as little as 4 to 5 days or, in some cases, 2 to 3 weeks later S
  • 26. Stem Cell Collection (Apheresis): Mobilisation 1 • The extent of mobilisation is determined through the patient’s WBC count. Serial measurements of the patient’s WBC count will assist the clinician in determining the appropriate time to commence collection procedures • Additionally, centres may use peripheral blood CD34+ cell levels as a surrogate for mobilisation status • Established thresholds for apheresis initiation may vary across centres, but typically range from 5 to 20 CD34+ cells/micro-litre • Although useful in estimating mobilisation efficacy, peripheral blood CD34+ counts can be variable within and across centres • Once mobilisation has reached an optimal level, a patient can be scheduled for sessions in the apheresis centre S
  • 27. Stem Cell Collection (Apheresis): Mobilisation 2 • An apheresis technician highly trained in stem cell collections is responsible for the equipment utilised in the collection process • Clinical nurses working in the apheresis unit are responsible for educating the patient about the stem cell collection process and monitoring patients for any adverse reactions. Patients are connected to the apheresis machine by their catheter • One lumen is used to draw blood out of the patient and into the machine • Here the blood is spun at high speeds in a centrifugation chamber housed within the cell separator machine • The desired stem cells are collected during the entire procedure, either in cycles or continuously, and the remaining blood components are returned to the patient through the second lumen of their catheter • This second lumen can additionally be used to administer intravenous fluids, electrolyte supplements, and medications to the patient S
  • 28. SEPARATORE CELLULARE Examples of apheresis machines . Cell separator: The cell separators used are the COMTEC Fresenius and COBE Spectra. Their function is to spin the blood in order to allow separation and collection of individual cellular components. The cell separators provide circuits and strictly sterile and disposable materials. S
  • 29. COBE SPECTRA SPIN COMTEC FRESENIUS SPIN Apheresis procedures are relatively safe. Although the mortality rate is quite low at an estimated 3 deaths per 10,000 procedures, apheresis is associated with some morbidity. Citrate is an anticoagulant used during the apheresis process to prevent blood clotting. Thus, one of the most common adverse effects seen during this procedure is citrate toxicity manifested as hypocalcaemia. This occurs due to binding of ionised serum calcium, which leads to hypocalcaemia. Signs and symptoms of citrate toxicity as well as its management are further described in the next table. Monitoring serum calcium levels prior to and throughout apheresis may decrease the likelihood of hypocalcaemia. Additional adverse effects of citrate toxicity include hypomagnesaemia, hypokalaemia, and metabolic alkalosis. The magnesium ion, like the calcium ion, is divalent and is bound by citrate. Declines in serum magnesium levels are often more pronounced and take longer to normalise compared to aberrations in calcium levels. Signs and symptoms of hypomagnesaemia, hypokalaemia, and metabolic alkalosis as well as their management are further described in the next table. S
  • 30. Common Apheresis Complications Adverse event Cause Signs & symptoms Corrective action Citrate toxicity Anticoagulant (citrate) given Hypocalcaemia Slow the rate of apheresis; increase during apheresis Common: dizziness & tingling in mouth area, hands the blood:citrate ratio; calcium & feet replacement therapy Uncommon: chills, tremors, muscle twitching & cramps, abdominal cramps, tetany, seizure, cardiac arrhythmia Hypomagnesaemia Slow the rate of apheresis; increase Common: muscle spasm or weakness the blood:citrate ratio; magnesium Uncommon: hypotonia & cardiac arrhythmia replacement therapy Hypokalaemia Slow the rate of apheresis; increase Common: weakness the blood:citrate ratio; potassium Uncommon: decrease in respiration rate replacement therapy Metabolic alkalosis Slow the rate of apheresis; increase Common: worsening of hypocalcaemia the blood:citrate ratio Uncommon: decrease in respiration rate Thrombocytopenia Platelets adhere to internal Low platelet count, bruising, bleeding Slow the rate of apheresis; increase surface of the apheresis the blood:citrate ratio machine Hypovolaemia Patient intolerant of large Dizziness, fatigue, light-headedness, tachycardia, Slow rate of apheresis session or shift in extracorporeal blood hypotension, diaphoresis, cardiac arrhythmia temporarily stop it; intravenous and plasma volumes fluid boluses Catheter Blood clot forms of catheter Inability to flush catheter, fluid collection under skin Reposition the catheter; gently malfunction is not well positioned to around catheter site, pain & erythema at catheter flush catheter; treat blood clot allow for adequate blood site; arm swelling, decrease in blood flow flow Infection Microbial pathogens enter Fever, chills, fatigue, red & erythematous skin Administer antibiotics; possibly bloodstream through around catheter; hypotension, position blood remove catheter catheter or catheter site cultures S
  • 31. Apheresis Complications: Hypovolaemia • Due to large fluctuations in blood volume during apheresis, patients may experience hypovolaemia • Prior to starting apheresis, baseline pulse and blood pressure are measured and continuously assessed at regular intervals. It is recommended that haemoglobin and haematocrit are also monitored • Patients at risk of developing hypovolaemia include those with anaemia, those with a previous history of cardiovascular compromise, and children or adults with a small frame • Preventative measures are aimed at minimising the extracorporeal volume shift by priming the apheresis machine with red blood cells and fresh frozen plasma in place of normal saline • Hypovolaemia may also be managed by providing intravenous fluid boluses and slowing the rate of flow on the apheresis machine • Another potential problem stemming from hypovolaemia is the development of a life-threatening cardiac dysrhythmia. If this occurs, apheresis should be interrupted and symptoms should subside before proceeding with collections S
  • 32. Cryopreservation • Many centres have cryopreservation laboratories that maintain collected stem cell products in liquid nitrogen until the time of the patient’s transplantation • Human cells can be cryopreserved in liquid nitrogen for several years without significant changes of their biological characteristics • A common cryopreservative used is dimethylsulfoxide (DMSO) which maintains cell viability by preventing ice crystal formation within the cells during storage • The collected product may be manipulated by a pharmacological, immunological, or physical method to reduce contamination with tumour cells. Quality testing is performed on collections to ascertain contamination with microbes as well as to determine the number of viable cells available for transplantation • Once a patient reaches their CD34+ collection goal, apheresis sessions are complete • Reaching minimum thresholds for CD34+ cell amounts is important as cell dose appears to positively correlate with engraftment and outcome • The total number of stem cells for the reinfusion may vary depending on the disease and the conditioning regimen used for the patient • The count of harvested stem cells determines if the patient has reached the target sufficient to support HD chemotherapy conditioning and cell transplantation S
  • 33. High-dose Chemotherapy (Conditioning Regimen) • To perform the transplant, the patient will undergo a hospitalisation period of 3-4 weeks in a protected environment • During this period, high-dose chemotherapy or radiotherapy will be performed as a conditioning regimen. The central venous access will be placed, generally in the subclavian vein, catheter or Port-a-Cath • Approximately 1 week prior to the transplant date, patients begin their preparative regimen in the ambulatory or inpatient unit of the hospital – This may consist of chemotherapy alone or chemotherapy in combination with radiation therapy – Chemotherapy agents selected for use during this time may differ from those used during previous cancer treatments or during mobilisation – The patient often benefits from cyto-reduction in their tumour following this phase of treatment – Due to the intensity of treatment, patients can experience ablation of their bone marrow stores and therefore need infusion of their previously collected cells as “rescue” therapy S
  • 34. Common Side Effects of Chemotherapy • The disorders most frequently associated with the administration of chemotherapy regimens in the conditioning phase depend on the scheme used and include: – Reduction of white blood cells with the potential risk of infection (Neutropenia) – Fever – Possible need for red blood cell transfusion and/or platelets (Anaemia) – Nausea/vomiting – Painful inflammation and ulceration of the mucous membranes lining the digestive tract (Mucositis) – Hair loss (Alopecia) S
  • 35. Detailed Side Effects of AHSCT Chemotherapy by Organ Organ Side Effect Intervention Gastrointestinal Nausea, vomiting, diarrhoea, Antiemetic drugs, mouth care regimens, pain tract weight loss, mucositis medication, nutritional supplementations Blood Pancytopenia* Antibiotics, blood transfusions Kidneys Haemorrhagic cystitis* Mesna, intravenous fluids, pain medications, bladder irrigation Liver Sinusoidal obstructive syndrome Diuretics, fluid restriction, intensive supportive (veno-occlusive disease)* care Brain / CNS Headache, tremors, seizures Pain medication, intensive supportive care Heart Oedema, hypertension Fluid restriction, diuretics, antihypertensive medication Lungs Atelectasis* Pulmonary hygiene (formerly known as pulmonary toilet) Skin Rash, discolouration Topical emollients, skin care, and bathing regimens *See notes for detailed descriptions S
  • 36. Stem Cell Transplant • Before high-dose chemotherapy is administered to the patient, the integrity of stored stem cells is verified • On the day of stem cell infusion, the previously collected product is removed from liquid nitrogen storage, thawed, and prepared for patient administration • The infusion itself can occur in an ambulatory or hospital setting. Prior to infusion, the product is rigorously inspected and tested for quality control measures, such as CD34+ cell counts and the presence of microbes • Several members of the health care team will also ensure that the product is the patient’s collected cells • The patient is prepared for the infusion by receiving pre-medications (e.g. an antihistamine, an antipyretic), having their intravenous line equipped to receive the cells, and being placed on medical equipment to monitor their vital signs throughout the procedure S
  • 37. Complications Associated With Autologous Stem Cell Infusion Adverse Event Signs & symptoms Corrective action Reactions to DMSO Common: Treatment of symptoms • Nausea • Vomiting • Abdominal cramping • Headache • Garlic aftertaste Rare: • Hypotension • Rapid heart rate • Shortness of breath • Fever • Neurological complications Oedema • Fluid retention Diuretics, fluid restriction • Puffiness • Weight gain • Hypertension Contamination of stem cell • Hypotension Antibiotics, intensive product • Rapid heart rate supportive care • Shortness of breath • Fever • Chills • Rigors • Positive blood culture for microbial pathogen S
  • 38. Engraftment & Recovery • During this critical time, the infused stem cells find their way back to the bone marrow microenvironment and repopulate depleted marrow stores • Post-transplant, cytokines are administered to enhance stem cell maturation and to re-establish blood cell components • The first sign of engraftment is the return of circulating WBCs to a sufficient level defined as an absolute neutrophil count (ANC) of > 500/mm for 3 consecutive days, which typically occurs 7-14 days after the stem cells have been infused into the patient • Increased platelet levels (absent of transfusion support) is another indicator of recovery, occurring at a later time point, averaging 2-3 weeks following the transplant S
  • 39. For information on the indications for transplant and the nurse’s role please see module two

Editor's Notes

  1. The stem cell transplant process can be summarised in 8 distinct phases (Figure 1): (1) administration of mobilisation agents, (2) mobilisation, (3) collection of mobilised cells using an apheresis machine, (4) preparation of product for storage, (5) cryopreservation/freezing of stem cells for use after preparative regimen, (6) administration of preparative regimen intended to kill any remaining cancer cells and make space for new cells, (7) stem cell transplantation back into the blood stream (with cells previously frozen), and (8) engraftment and recovery (infused stem cells mature into functional blood components such as neutrophils and platelets).
  2. LDH – lactate dehydrogenase
  3. Each apheresis session lasts approximately 2-5 hours during which upwards to 30 litres of blood, or 6 times the average total human blood volume, is processed. Collections can occur on a daily basis until the target CD34+ levels are achieved. The apheresis process can last for up to 4 days depending on patient characteristics and the mobilisation regimen utilised.
  4. Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets.Haemorrhagic cystitis is diffuse inflammation of the bladder leading to dysuria, haematuria, and haemorrhage.Hepatic veno-occlusive disease or veno-occlusive disease (VOD) is a condition in which some of the small veins in the liver are blocked. The name sinusoidal obstruction syndrome is now preferred if VOD happens as a result of chemotherapy or bone marrow transplantation.Atelectasis is defined as the collapse or closure of alveoli resulting in reduced or absent gas exchange. It may affect part or all of one lung.
  5. Until engraftment occurs, patients are at an increased risk of infections, so precautions must be taken to avoid exposure to microbial pathogens. Patients often require supportive care strategies and therapies, including administration of antiemetics, pain medications, antibiotics, and nutrition support to ameliorate consequences following the highdose chemotherapy preparative regimen and the subsequent prolonged period of pancytopenia.