Cancer Treatment Modalities: Hematopoietic Stem Cell Transplantation Flashcards

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
Q

What labs do we look at for a potential transplant recipient?

A
CBC
BMP (liver and renal) 
Coags
ABO/RH type 
Pregnancy test
Full workup for infectious diseases 
HLA testing for allogenic recipients
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26
Q

Organ function tests for potential transplant recipient?

A

Cardiac
Electrocardiogram for EF
Pulmonary tests
Dental eval

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27
Q

Disease eval tests for potential transplant recipient?

A

Bone marrow biopsy/aspiration
Radiographic scans
Lumbar puncture
Immunoglobulins

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28
Q

Psychosocial eval for potential transplant recipient?

A

Comprehension of process, risk, adverse effects
Ability to comply
Social and spiritual issues
Family concerns

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29
Q

Financial eval for potential transplant recipient?

A

Reimbursement assessment
Personal financial resources
Impact of absence from work (pts and caregivers)

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30
Q

What treatment course is given to patient to prepare for transplant?

A

Single of combination chemotherapy with or without total body irradiation (TBI)

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31
Q

What is the purpose of giving chemo/radiation to prepare patient for transplant?

A

Used to eliminate disease or completely ablate the marrow

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32
Q

Myeloablative regimens =

A

The administration of lethal doses of therapy to eradicate cancer cells and produce severe immunosuppression before transplant

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33
Q

What is the benefit of a myeloablative regimen?

A

decreases ability of host to reject donor graft, enhance engraftment

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34
Q

Non-myeloablative regiments or reduced intensity (RIC regimens =

A

Uses reduced doses of chemo and TBI before transplant

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35
Q

When are non-myeloablative regimens used vs. myeloablative

A

Older patients
Comorbid conditions
Less toxic

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36
Q

Dimethyl Sulfoxide (DMSO)

A

A preservative present in processed stem cells that causes reactions during infusion -> pts given premeds and aggressive hydration

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37
Q

Adverse effects of infusion

1) Are the reactions intense?
2) Urine
3) Mouth
4) Cardiopulmonary

A

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

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38
Q

How do we decrease the risk for adverse effects during infusion?

A

Less common with fresh cells transplantation (less time preserved)

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39
Q

What are the two signs of successful hematopoietic stem cell transplantation?

A

1) Engraftment

2) Chimerism (for allogenic pts)

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40
Q

What changes in the lab results to show successful engraftment?

A

ANC > 500/mm3
Platelets >20,000/mm3

Shows that stem cells are in the marrow space and reproducing

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41
Q

General timeline for engraftment for Autologous and Allogenic transplants?

A

14-21 days

1-30 days when nonmyeloablative tx used

> 30 days for umbilical cord source

42
Q

Major complication of HSCT?

A

GVHD

43
Q

Graft vs Host Disease =

A

A complex immune reation between host (patient) and donor cells -> results in graft failure, disease relapse, fatal infection

44
Q

Development of Graft Vs. Host disease is a __ step process

A

3

45
Q

Step 1 in GVHD

A

Host tissue (mainly skin, GI tract, liver) is damaged by the conditioning regimen leading to inflammatory cytokines

46
Q

Step 2 in GVHD

A

After a complex process, donor T cells activated, further enhancing inflammatory process

47
Q

Step 3 in GVHD

A

Local tissue damage and death by donor T cells and continued cytokine simulation of T-cell activation

48
Q

How do you diagnose GVHD?

A

By biopsy of affected organs

49
Q

Risk factors for development of GVHD

A

Matched unrelated donor
Haploididentical transplants
Older patients
Peripheral stem collection

50
Q

What organs are affected by GVHD?

A

Skin
GI tract
Liver

51
Q

Skin effects of GVHD

A

Maculopapular rash with or without pruritis
First appears on palms, soles, neck, ears, shoulders
Erythoderma and bullous formation

52
Q

GI tract effects of GVHD

A

N/V, anorexia, diarrhea (lower GI)

53
Q

Liver effects of GVHD

A

Elevated bilirubin

Weight gain

54
Q

Tx for GVHD

A

Corticosteroids*

Salvage therapies include photopheresis, monoclonal antibodies, antithymocyte globulin infusion

55
Q

Types of HSCT complications (4)

A

Hematologic
Gastrointestinal
Renal, Hepatic
Cardiopulmonary

56
Q

Hematologic complications (5)

The most common complication

A
Neutropenia 
Thrombocytopenia 
Anemia 
Engraftment 
Chimerism
57
Q

Neutropenia

1) Induced by?
2) ANC of
3) Duration of neutropenia depends on

A

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
Q

Pre-engraftment is usually - days after transplantation

Primary risk factors for infection are (3)

A

0-15

Profound neutropenia
Alteration in skin integrity
Mucosal barrier toxicity

59
Q

Types of infections that HSCT patients are prone to in pre-engraftment phase (3)

A

1) Bacterial
2) Fungal
3) Viral

60
Q

Bacterial infections

1) 2 types
2) common sites
3) Prophylaxis medication

A

1) gram positive and negative
2) oral mucosa, cvc catheter
3) quilonlone

61
Q

Fungal infections

1) 2 species
2) Reduce the risk by using
3) Prophylaxis medication

A

1) Candidia albicans (stomatitis), Aspergillus (pulmonary)
2) HEPA filter and positive pressure rooms
3) Fluconazole

62
Q

Viral infections

1) 2 types
2) HSV usually presents itself in ____
3) Prophylaxis medication

A

1) Herpes simplex virus
2) stomatitis
3) Valacyclovir

Cytomegalovirus is more common in allogeneic transplant recipients

63
Q

Which type of HSCT is at greater risk for infection?

A

Allogeneic > Autologous

64
Q

Greater risk for what types of infections?

A

Nonbacterial (fungal and viral)

-Reactivation of latent viruses such as CMV and epstein barris common

65
Q

Common infections

A

Streptococcus pneumoniae
Haemophilus influenzae
Sinusitis
Varicella zoster virus

-Reactivation of latent viruses such as CMV and epstein barris common

66
Q

Why does thrombocytopenia persist post HSCT?

may indicate poor prognosis

A

Megakaryocytes are last to engraft for both types of transplants

  • full platelet recovery usually 1-3 months post transplant
67
Q

Cause of anemia post HSCT is from?

A

Conditioning regimen*

Other causative factors - bleeding, renal failure insufficiency dt therapies, hemolysis from ABO incompatibility

68
Q

Engraftment is defined as an ANC and platelet count of?

A

> 500/mm3

>20,000/mm3

69
Q

GI complications from HSCT (3)

A

N/V, Retching, Anorexia
Mucositis
Diarrhea

70
Q

Causes of N/V, Retching, Anorexia post HSCT

A
  • High dose chemo*
  • GVHD
  • Meds used for supportive therapy
  • Electrolyte and nutritional imbalances
  • Esophageal tears
  • Decreased elimination of meds
  • Aspiration PNA
71
Q

Management of mucositis is important because?

A

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
Q

Melphalan =

A

A conditioning agent used for autologous transplantation that has a high incidence of causing mucositis

73
Q

Nursing considerations for mucositis

A

Pain management is critical

Oral care and assessment

74
Q

Causes of diarrhea post HSCT

A

Multifactorial

  • conditioning regimens
  • acute GVHD
  • infections
75
Q

Management of diarrhea post HSCT

A
Accurate I/O
Fluid and Electrolyte replacement 
Monitor for s/s of dehydration 
Blood loss or hemorrhage
Assess efficacy of pharmacologic interventions
76
Q

The main Renal complication from HSCT

A

Acute Renal Toxicity

77
Q

Renal Toxicity from HSCT

1) common adverse affect, primarily from which pre-regimen?
2) 1/3 of pts will require _____

A

1) Myeloablative regimen

2) dialysis

78
Q

Renal Toxicity causes (5)

1) ______ regimen
2) Nephrotoxic _____ therapy
3) S____
4) Infusion of ____ ____
5) _______ immunosuppresive agents (3)

A

1) Conditioning
2) Antibiotic
3) Sepsis
4) Stem cells
5) Calcineurin

Tacrolimus
Cyclosporine
Volume depletion

79
Q

Effect of Calcineurin agents on the kidneys?

A

Vasoconstriction and decreases vasodilators -> decreased renal blood flow and GFR -> interstitial fibrosis and tubular atrophy

80
Q

Increased incidence of acute renal toxicity with patients that have (2)

A

TBI (total body irradiation)

High trough levels

81
Q

Tx of acute renal toxicity post HSCT

A

Vigorous hydration

Close monitoring of trough levels

82
Q

High-dose cyclophosphamide therapy usually causes what and how?

A

Hemorrhagic cystitis

The metabolite acrolein binds to wall of bladder -> bleeding and severe clot formation

83
Q

Sx of hemorrhagic cystitis

A

Dysuria
Frequency
Urgency

84
Q

Tx of hemorrhagic cystitis

1) what drug?
2) vigorous ______

A

Mesna (neuroprotectant)

hydration

85
Q

Hemorrhagic cystitis that occurs at later point of transplant process usually occurs from what viruses?

A

Cytomegalovirus
BK virus
Adenovirus

86
Q

Main Hepatic complication of HSCT

A

Hepatotoxicity

87
Q

Causes of hepatotoxicity from HSCT

1) _V_D
2) HSOS
3) F___ and V____ infections

A

1) GVHD
2) Hepatic sinusoidal obstructive syndrome (venous occlusive disease)
3 Fungal, Viral

88
Q

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)

A

1) 2-4, 100
2) Old age, mismatched donor (matched unrelated donor)
3) Jaundice, severe upper quadrant pain, hepatomegaly
4) high-dose corticosteroids

89
Q

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)

A

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
Q

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 _ _ _

A

1) Busulfan
2) Carmustine
3) aGVHD
4) Methotrexate
5) Immunosuppression
6) TBI

91
Q

Cardiac complications of HSCT are uncommon and usually occur as a result of cardiotoxic effects of what 2 drugs?

A

Cyclophosphamide

Anthracyclines

92
Q

Cyclophasphamide and Anthracyclines cause what cardiac effects (2)

A

Cardiomyopathy

Sx of CHF

93
Q

High doses of cyclophosphamide cause what severe cardiac effects (2)

A

Pericardial effusion

Tamponade

94
Q

Infusion of stem cells may cause what cardiac effect?

Bacterial and fungal infections may cause what cardiac effect?

A

Arrhythmia (SVT)

Endocarditis

95
Q

Pulmonary complications of HSCT

1) Classified as either (2)

A

1) Infectious or Noninfectious

96
Q

Infectious causes of pulmonary complications

A

Viral (CMV, varicella, zoster, community acquired respiratory, adenovirus)

Protozoans

Myocobacterial organisms

97
Q

Non-infectious causes of pulmonary complications

A
Interstitial pneumonitis 
Diffuse alveolar hemorrhage 
Postengraftment respiratory syndrome 
Bronchiolitis obliterans syndrome
Bronchiolitis obliterans pneumonia
98
Q

Diagnosis of pulmonary complications made by what tests?

A

Chest Xray, CT scan

Bronchoscopy with lavage for indentification of infectious agent

99
Q

Treatment of pulmonary complications

Infectious =
Noninfectious =

A

Antimicrobials

Corticosteroids

100
Q

Late effect of HSCT

A

Risk for secondary malignancy (3)

AML, MDS
PTLD
Solid tumors (radiation induced: melanoma, oral cavity bone, thyroid, breast)