Cancer Treatment Modalities: Hematopoietic Stem Cell Transplantation Flashcards

(100 cards)

1
Q

What is Hematopoietic stem cell transplatantation (HSCT)?

A

Hematopoietic stem cells (HSCs) to self renew, proliferate, and mature into functional blood cells and establish immunity

-provides constant levels of blood cells in peripheral blood needed for administration of high-dose therapy

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2
Q

Major maker of the HSC

A

CD34

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3
Q

Autologous stem cell transplantation =

A

Source of cells is self (patient)

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4
Q

Allogeneic stem cell transplantation =

A

Source of cells is human leukocyte antigen (HLA)- matched donor

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5
Q

Risks/Benefits of Autologous

A

No graft vs host disease
No benefit of graft vs tumor effect
Potential contamination of graft w cancer cells

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6
Q

Risks/Benefits of Allogeneic

A

Complications of infection or long term organ damage from tax regimens
Graft vs host disease
No malignant cells in graft
Length to time to locate compatibility donor

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7
Q

Synegenic stem cell transplant =

A

Source from identical twin

Rarely used bc of high relapse rate

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8
Q

What are HLAs?

A

Human Leukocyte Antigens are found on surface of white blood cells and other tissues in the body -> can differentiate from non self

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9
Q

What does two ppl sharing the same HLA mean?

A

Their white cells and tissues are immunologically and histiologically compatible with each other

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10
Q

Types of Cancers that use autologous stem cell transplants

1) Hematologic (3)
2) Solid (2)

A

1) Multiple Myeloma, Hodgkin lymphoma, Non-Hodgkins lymphoma
2) Neuroblastoma, Germ cell tumors

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11
Q

Types of Cancers that use Allogeneic stem cell transplants (6)

A

Hematologic

  • Leukemias
  • Non-Hodgkins Lymphoma
  • Myelodyspastic syndrome
  • Aplastic anemia
  • Sickle cell disease
  • Thalasemia
  • Falconi anemia
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12
Q

The genes for HLAs are located on chromosome __ and are inherited as a single _____ from each ____

A

6, haplotype, parent

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13
Q

Surface proteins responsible for assisting the acquired immune response to recognize non-self molecules =

A

Major Histocompatibility complex (MHC)

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14
Q

The different classes of genes within the MHC (3)

A

Class I: HLA-A, HLA-B, HLA-C
Class II: HLA DR, HLA DP, HLA DQ

ex) individuals can have more than 20 varieties and more than 10,000 HLA types

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15
Q

Why is it important that the donors MHC sets match the patients?

A

Graft rejection, Graft vs. Host disease

If a T-lymphocyte recognizes a non-self MHC, it will rally immune cells to destroy the cell that bears it

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16
Q

HLAs vs. MHC?

A

HLA is the human body’s version of MHC

MHC’s are found in all vertebrates

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17
Q

Sources of stem cell collection (3)

A

Bone Marrow
Peripheral blood
Umbilical

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18
Q

Pluripotent =

A

(of an immature or stem cell) capable of giving rise to several different cell types

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19
Q

Characteristics of Bone Marrow stem cell collection

1) Rich in ____ stem cells
2) Harvested from what part of donors body?
3) Procedure is how long?
4) Total fluid obtained?
5) Adverse effects of procedure?
6) After collection how is the fluid processed?
7) How soon is the product infused into the patient?
8) Disadvantages?

A

1) pluripotent
2) posterior iliac crest
3) 1-2 hours
4) 500-1,000ml
5) postop pain, effects of anesthesia, infection, bleeding, hematoma
6) filtered to remove fat and bone particles, then further processing in stem cell lab
7) Ideally same day, but can be cryopreserved for a later date
8) surgery, longer duration for engraftment of stem cells

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20
Q

Characteristics of Peripheral stem cell collection

1) Stem cells ___ usually ___ in peripheral blood system
2) How do stem cells moved from marrow space to the periphery?
3) The cells are collected by what process?

A

1) not present
2) using high doses of granulocyte-colony stimulating factor administered 4-6 days before collection
3) Apheresis

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21
Q

Apheresis for peripheral stem cells

1) What machine is used?
2) Access of patient and donor?
3) Where is this procedure done?
4) Adverse effects?
5) When is it used?
6) Advantage?
7) Disadvantage?

A

1) Centrifuge (removes CD-34 stem cells from blood and returns blood back to donor)
2) Patient uses tunneled multi-lumen catheter, Donor has PIV, fem line if PIV not adequate
3) Outpatient, just 1 day
4) Hypocalcemia (bc sodium citrate in apheresis line to prevent clotting), Hypovolemia, Thrombocytopenia
5) Same day or cryopreserved
6) Shorter time for hematologic recovery and engraftment of cells
7) Risk for GVHD

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22
Q

Characteristics of Umbilical stem cell collection

1) When and from what is collected?
2) Where is it cryopreserved?
3) Advantage
4) Disadvantage

A

1) At birth, collected from umbilical cord and placenta
2) cord blood bank
3) Rich in stem cells, low risk for GVHD
4) Longer duration of myelosuppression and time of engraftment of cells

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23
Q

Minimum collection of stem cells from bone marrow vs peripheral sources

A

1-4 x 108cells/kg

2-10 x 108cells/kg

= more for peripheral

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24
Q

Prior to transplant, patient is clinically evaluated for what aspects of health and life? (5)

A

1) Labs
2) Organ function
3) Diseases
4) Psychosocial
5) Financial

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25
What labs do we look at for a potential transplant recipient?
``` CBC BMP (liver and renal) Coags ABO/RH type Pregnancy test Full workup for infectious diseases HLA testing for allogenic recipients ```
26
Organ function tests for potential transplant recipient?
Cardiac Electrocardiogram for EF Pulmonary tests Dental eval
27
Disease eval tests for potential transplant recipient?
Bone marrow biopsy/aspiration Radiographic scans Lumbar puncture Immunoglobulins
28
Psychosocial eval for potential transplant recipient?
Comprehension of process, risk, adverse effects Ability to comply Social and spiritual issues Family concerns
29
Financial eval for potential transplant recipient?
Reimbursement assessment Personal financial resources Impact of absence from work (pts and caregivers)
30
What treatment course is given to patient to prepare for transplant?
Single of combination chemotherapy with or without total body irradiation (TBI)
31
What is the purpose of giving chemo/radiation to prepare patient for transplant?
Used to eliminate disease or completely ablate the marrow
32
Myeloablative regimens =
The administration of lethal doses of therapy to eradicate cancer cells and produce severe immunosuppression before transplant
33
What is the benefit of a myeloablative regimen?
decreases ability of host to reject donor graft, enhance engraftment
34
Non-myeloablative regiments or reduced intensity (RIC regimens =
Uses reduced doses of chemo and TBI before transplant
35
When are non-myeloablative regimens used vs. myeloablative
Older patients Comorbid conditions Less toxic
36
Dimethyl Sulfoxide (DMSO)
A preservative present in processed stem cells that causes reactions during infusion -> pts given premeds and aggressive hydration
37
Adverse effects of infusion 1) Are the reactions intense? 2) Urine 3) Mouth 4) Cardiopulmonary
1) Minor, resolves in 1-2 days 2) Pink tinged/cherry red urine from breakdown of rbcs and stem cells 3) Garlic breath or taste in mouth bc of breakdown of DMSO 4) Hypo/Hypertension, Brady/Tachycardia, Chest tightness, Dyspnea, Cough, Flushing, hives, fever, N/V, diarrhea
38
How do we decrease the risk for adverse effects during infusion?
Less common with fresh cells transplantation (less time preserved)
39
What are the two signs of successful hematopoietic stem cell transplantation?
1) Engraftment | 2) Chimerism (for allogenic pts)
40
What changes in the lab results to show successful engraftment?
ANC > 500/mm3 Platelets >20,000/mm3 Shows that stem cells are in the marrow space and reproducing
41
General timeline for engraftment for Autologous and Allogenic transplants?
14-21 days 1-30 days when nonmyeloablative tx used >30 days for umbilical cord source
42
Major complication of HSCT?
GVHD
43
Graft vs Host Disease =
A complex immune reation between host (patient) and donor cells -> results in graft failure, disease relapse, fatal infection
44
Development of Graft Vs. Host disease is a __ step process
3
45
Step 1 in GVHD
Host tissue (mainly skin, GI tract, liver) is damaged by the conditioning regimen leading to inflammatory cytokines
46
Step 2 in GVHD
After a complex process, donor T cells activated, further enhancing inflammatory process
47
Step 3 in GVHD
Local tissue damage and death by donor T cells and continued cytokine simulation of T-cell activation
48
How do you diagnose GVHD?
By biopsy of affected organs
49
Risk factors for development of GVHD
Matched unrelated donor Haploididentical transplants Older patients Peripheral stem collection
50
What organs are affected by GVHD?
Skin GI tract Liver
51
Skin effects of GVHD
Maculopapular rash with or without pruritis First appears on palms, soles, neck, ears, shoulders Erythoderma and bullous formation
52
GI tract effects of GVHD
N/V, anorexia, diarrhea (lower GI)
53
Liver effects of GVHD
Elevated bilirubin | Weight gain
54
Tx for GVHD
Corticosteroids* Salvage therapies include photopheresis, monoclonal antibodies, antithymocyte globulin infusion
55
Types of HSCT complications (4)
Hematologic Gastrointestinal Renal, Hepatic Cardiopulmonary
56
Hematologic complications (5) The most common complication
``` Neutropenia Thrombocytopenia Anemia Engraftment Chimerism ```
57
Neutropenia 1) Induced by? 2) ANC of 3) Duration of neutropenia depends on
1) conditioning regimen 2) <100 3) conditioning regimen, # of CD34 cells per kilogram, use of growth factors, post transplant complications, hx of chemo and rt
58
Pre-engraftment is usually _-_ days after transplantation Primary risk factors for infection are (3)
0-15 Profound neutropenia Alteration in skin integrity Mucosal barrier toxicity
59
Types of infections that HSCT patients are prone to in pre-engraftment phase (3)
1) Bacterial 2) Fungal 3) Viral
60
Bacterial infections 1) 2 types 2) common sites 3) Prophylaxis medication
1) gram positive and negative 2) oral mucosa, cvc catheter 3) quilonlone
61
Fungal infections 1) 2 species 2) Reduce the risk by using 3) Prophylaxis medication
1) Candidia albicans (stomatitis), Aspergillus (pulmonary) 2) HEPA filter and positive pressure rooms 3) Fluconazole
62
Viral infections 1) 2 types 2) HSV usually presents itself in ____ 3) Prophylaxis medication
1) Herpes simplex virus 2) stomatitis 3) Valacyclovir Cytomegalovirus is more common in allogeneic transplant recipients
63
Which type of HSCT is at greater risk for infection?
Allogeneic > Autologous
64
Greater risk for what types of infections?
Nonbacterial (fungal and viral) -Reactivation of latent viruses such as CMV and epstein barris common
65
Common infections
Streptococcus pneumoniae Haemophilus influenzae Sinusitis Varicella zoster virus -Reactivation of latent viruses such as CMV and epstein barris common
66
Why does thrombocytopenia persist post HSCT? | may indicate poor prognosis
Megakaryocytes are last to engraft for both types of transplants - full platelet recovery usually 1-3 months post transplant
67
Cause of anemia post HSCT is from?
Conditioning regimen* Other causative factors - bleeding, renal failure insufficiency dt therapies, hemolysis from ABO incompatibility
68
Engraftment is defined as an ANC and platelet count of?
>500/mm3 | >20,000/mm3
69
GI complications from HSCT (3)
N/V, Retching, Anorexia Mucositis Diarrhea
70
Causes of N/V, Retching, Anorexia post HSCT
- High dose chemo* - GVHD - Meds used for supportive therapy - Electrolyte and nutritional imbalances - Esophageal tears - Decreased elimination of meds - Aspiration PNA
71
Management of mucositis is important because?
*because there is no treatment proven efficacious for prevention or symptoms* >70% of patients experience it post HSCT - can occur at any location along GI tract - mucositis causes alteration in mucosal barrier can result in systemic infections - reactivation of HSV
72
Melphalan =
A conditioning agent used for autologous transplantation that has a high incidence of causing mucositis
73
Nursing considerations for mucositis
Pain management is critical | Oral care and assessment
74
Causes of diarrhea post HSCT
Multifactorial - conditioning regimens - acute GVHD - infections
75
Management of diarrhea post HSCT
``` Accurate I/O Fluid and Electrolyte replacement Monitor for s/s of dehydration Blood loss or hemorrhage Assess efficacy of pharmacologic interventions ```
76
The main Renal complication from HSCT
Acute Renal Toxicity
77
Renal Toxicity from HSCT 1) common adverse affect, primarily from which pre-regimen? 2) 1/3 of pts will require _____
1) Myeloablative regimen | 2) dialysis
78
Renal Toxicity causes (5) 1) ______ regimen 2) Nephrotoxic _____ therapy 3) S____ 4) Infusion of ____ ____ 5) _______ immunosuppresive agents (3)
1) Conditioning 2) Antibiotic 3) Sepsis 4) Stem cells 5) Calcineurin Tacrolimus Cyclosporine Volume depletion
79
Effect of Calcineurin agents on the kidneys?
Vasoconstriction and decreases vasodilators -> decreased renal blood flow and GFR -> interstitial fibrosis and tubular atrophy
80
Increased incidence of acute renal toxicity with patients that have (2)
TBI (total body irradiation) High trough levels
81
Tx of acute renal toxicity post HSCT
Vigorous hydration Close monitoring of trough levels
82
High-dose cyclophosphamide therapy usually causes what and how?
Hemorrhagic cystitis The metabolite acrolein binds to wall of bladder -> bleeding and severe clot formation
83
Sx of hemorrhagic cystitis
Dysuria Frequency Urgency
84
Tx of hemorrhagic cystitis 1) what drug? 2) vigorous ______
Mesna (neuroprotectant) | hydration
85
Hemorrhagic cystitis that occurs at later point of transplant process usually occurs from what viruses?
Cytomegalovirus BK virus Adenovirus
86
Main Hepatic complication of HSCT
Hepatotoxicity
87
Causes of hepatotoxicity from HSCT 1) _V_D 2) HSOS 3) F___ and V____ infections
1) GVHD 2) Hepatic sinusoidal obstructive syndrome (venous occlusive disease) 3 Fungal, Viral
88
Hepatic aGVHD 1) Usually occurs _-_ weeks after transplantation but may occur up to the ____ day mark 2) Risk factors (2) 3) Severe symptoms (3) 4) Treatment (1)
1) 2-4, 100 2) Old age, mismatched donor (matched unrelated donor) 3) Jaundice, severe upper quadrant pain, hepatomegaly 4) high-dose corticosteroids
89
HSOS (Hepatic Sinusoidal obstructive syndrome) 1) Total _ _ and conditioning regimens containing (3) 2) Effects of these drugs on the liver 3) Occurs in the first _ weeks after transplant 4) Triad of symptoms 5) Two systems used to diagnose 6) Treatment 7) Preventative drugs (3)
1) TBI; Busulfan, melphalan, cyclophosphamide 2) injury to endothelial tissue -> thrombosis within sinusoids and venules -> decreased blood flow 3) 4 4) Rapid weight gain, elevated bilirubin, painful hepatomegaly 5) Seattle and Baltimore 6) Diuretics, Symptom management 7) Urodeoxycholic acid (Ursodiol), Antithrombin III, Glutamine
90
Neurologic complications from HSCT causes 1) B____ use (can produce seizures; requires use of prophylactic anti-seizure meds) 2) C_____ use 3) Severe a_ _ _ 4) Prior hx of intrathecal _____ 5) Prolonged ______ 6) Conditioning regimens that include _ _ _
1) Busulfan 2) Carmustine 3) aGVHD 4) Methotrexate 5) Immunosuppression 6) TBI
91
Cardiac complications of HSCT are uncommon and usually occur as a result of cardiotoxic effects of what 2 drugs?
Cyclophosphamide Anthracyclines
92
Cyclophasphamide and Anthracyclines cause what cardiac effects (2)
Cardiomyopathy Sx of CHF
93
High doses of cyclophosphamide cause what severe cardiac effects (2)
Pericardial effusion Tamponade
94
Infusion of stem cells may cause what cardiac effect? Bacterial and fungal infections may cause what cardiac effect?
Arrhythmia (SVT) Endocarditis
95
Pulmonary complications of HSCT 1) Classified as either (2)
1) Infectious or Noninfectious
96
Infectious causes of pulmonary complications
Viral (CMV, varicella, zoster, community acquired respiratory, adenovirus) Protozoans Myocobacterial organisms
97
Non-infectious causes of pulmonary complications
``` Interstitial pneumonitis Diffuse alveolar hemorrhage Postengraftment respiratory syndrome Bronchiolitis obliterans syndrome Bronchiolitis obliterans pneumonia ```
98
Diagnosis of pulmonary complications made by what tests?
Chest Xray, CT scan Bronchoscopy with lavage for indentification of infectious agent
99
Treatment of pulmonary complications Infectious = Noninfectious =
Antimicrobials | Corticosteroids
100
Late effect of HSCT
Risk for secondary malignancy (3) AML, MDS PTLD Solid tumors (radiation induced: melanoma, oral cavity bone, thyroid, breast)