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Oncology Exam 2 > HSCT > Flashcards

HSCT Flashcards

1
Q

Which cell are we interested in for HSCT?

A

Pluripotent stem cell (PPSC)

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2
Q

Transplant using OWN stem cells

A

autologous

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3
Q

Transplant using an outside source of stem cells

A

Allogeneic

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4
Q

Identical twin stem cell donor

A

syngeneic

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5
Q

What type of allogenic stem cell transplants sources are there?

A

Identical twin: syngeneic

Sibling: MSD

matched related: MRD

Unrelated: MUD

Haploidentical: haplo

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6
Q

T/F in autologous transplant HSCT is a cure

A

False!

Used as rescue therapy!

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7
Q

What type of transplant would be from a parent/donot to each other?

A

Haploidentical

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8
Q

Which type of HSCT is myeloablative?

A

autologous

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9
Q

T/F a transplant receipient stays at the hospital longer if they underwent autologous transpalnt

A

False

Allogenic: 3 week stay

Autologous: 3-4 week stay

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10
Q

Rationale for autologous transplant

A

Re-infusion of stem cells eliminates the dose limiting toxicity of myelosuppression

  • use HD chemo to kill more cells!
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11
Q

T/F In autologous HSCT you ONLY use filgrastim prior to stem cell collection

A

False!

can use chemo + filgrastim

or each individually

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12
Q

T/F in autologous HSCT the stem cells must be fresh

A

False

Stem cells are frozen!

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13
Q

Rational for allogenic transplant

A

Provide functional new bone marrow

Graft vs tumor effect: conditioning provides initial immunosuppression

  • asume most antitumor activity is derived from donor T cells
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14
Q

Allogeneic transplant gets its antitumor activity from what?

A

Donor T cells

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15
Q

T/F you do not use chemotherapy in a donor in allogeneic HSCT

A

True!

Not ethical!

only use filgrastim!

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16
Q

T/F In allogeneic HSCT stem cells must be fresh from the donor

A

true!

have 24 hours

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17
Q

Why is it important to find the perfect donor for HSCT?

A
  • decreases risk of GVHD
  • impact on survival
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18
Q

What is the most important factor in HSCT donation?

A

Having a good HLA match!

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19
Q

HLA-I cells are found where?

A

all nucleated cells

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20
Q

HLA-II cells are found where?

A

macrophages

B lymphocytes

activated T lymphocytes

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21
Q

How many HLA antigens does each person have?

A

8

4 from each parent

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22
Q

What is a perfect match for HSCT?

A

8/8 HLA

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23
Q

HLA mismatch correlates with what?

A
  • risk of graft failure
  • risk of GVHD
  • survival
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24
Q

Which diesease states do you use autologous stem cell transplant?

A

Lymphomas

MM

Germ cell tumors

brain tumors- peds

Neuroblastoma-peds

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25
Q

Which disease states do you use allogeneic stem cell transplant?

A

Acute leukemia

Severe aplastic anemia

Sickle cell anemia

metabolic disorders- peds

SCID

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26
Q

Describe the timing of HSCT if you have high risk disease

A
  1. diagnosis
  2. chemo
  3. remission
  4. HSCT
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27
Q

Describe the timing of HSCT if you have a lower risk of disease

A
  1. diagnosis
  2. chemo
  3. remission
  4. wait and watch
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28
Q

T/F if you have SCID or metabolic disorders you can have HSCt before chemo

A

True!

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29
Q

What are the 3 phases of stem cell transplant?

A

Stem cell collection

Transplant

Post transplant

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30
Q

What 3 sites can you collect stem cells from?

A

peripheral blood

bone marrow

umbilical

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31
Q

What is the surrogate marker for stem cell collection?

A

CD34 antigen

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32
Q

Why do we care about the number of cells the recipient has prior to transplant?

A

correlated with recovery!

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33
Q

What is the minimum number of cells of the recipient prior to HSCT?

A

2 x 106 cells/kg

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34
Q

What is the target number of cells in the recipient prior to HSCT?

A

5 x 106 cells/kg

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35
Q

What is the main advantage of using stem cells from the bone marrow?

A

Decreased risk of chronic GVHD

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36
Q

Describe using stem cells from bone marrow

A
  • general anesthesia
  • takes 1-2 hours
  • multiple aspirations from iliac crests: PAINFUL
  • Large volume needed
  • given to recipient after harvest
  • longer time to engraft
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37
Q

What are some advantages of using stem cells from the peripheral blood?

A
  • no general anesthesia
  • small volume needed
  • rapid engraftment
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38
Q

Describe using stem cells from the peripheral blood

A
  • utilize mobilization techniques prior to harvest
  • collection may be 3-5 hours per day
  • may need multiple days
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39
Q

Which source of stem cells is preferred for autologou transplants and for most allogeneic transplants?

A

Peripheral blood

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40
Q

T/F using stem cells from the peripheral blood has a 2x higher risk of chronic GVHD

A

True

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41
Q

What does stem cell mobilization do?

What do you use?

A

Stimulates stem cell production

Use chemo, growth factors or both!

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42
Q

Who do you need to mobilize stem cells in?

A

Peripheral blood stem cell collection

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43
Q

What growth factors can be used in mobilization regimen of HSCT?

A

Filgrastim

Sargramostim

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44
Q

What is the most common chemo agent used in mobilization regimens for HSCT?

A

cyclophosphamide

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45
Q

When using filgrastim for mobilization, what side effects do you need to warn the patient about?

A

bone pain: try claritin

splenic enlargement: no vigorous activity

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46
Q

What factors influence mobilization?

A
  • tumor infiltrate in BM
  • fibrotic BM
  • history of pelvic or abdominal irradiation
  • marrow hypocellularity
  • prior exp to SC toxins: alkylating agents, nitrosureas
  • >70 yo
  • baseline platelet <150k
  • # of prior chemo regimens
  • duration of exp to chemo
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47
Q

What drug inhibits the chemokine receptors that act as anchors stem cells to the marrow?

A

Plerixafor (Mozobil)

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48
Q

Who would you use plerixafor (Mozobil) in?

A
  • failed prior mobilization attempt
  • few PBSC after 3 days of GCSF
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49
Q

T/F when using plerixafor you do not continue using growth factors

A

False!

Continue morning growth factor doses!

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50
Q

Toxicity of plerixafor

A

Diarrhea

Nausea

Injection site reactions

51
Q

Toxicity of growth factors

A

Bone pain

Fever

Injection site pain/reactions

Splenic enlargement

52
Q

Main toxicity of cyclophosphamide

A

Hemorrhagic cystitis

N/V

53
Q

What are some advantages of using stem cells from umbilical cord?

A
  • less stringent HLA requirements
  • decreased severe GVHD
  • decreased viral contamination
  • no risk to donor
  • product available immediately
54
Q

What are some disadvantages of using stem cells from umbilical cord?

A
  • limited number of cells
  • longer to engraft
  • no second donation
  • higher risk of graft failure
55
Q

When are conditioning regimens done in HSCT?

A

immediately before transplant

56
Q

What are the goals of conditioning regimens?

A
  • Kill as many tumor cells as possible: autologous, allogeneic
  • Immunosuppression to prevent GVHD: allogeneic
57
Q

What makes up a conditioning regimen?

A

chemo +/- total body irradiation (TBI)

58
Q

T/F patients must be healthy prior to HSCT to have myeloablative conditioning regimens

A

True!

59
Q

Main toxicities of melphalan

A

Mucositis

GI toxicity

60
Q

Acute toxicities of TBI

A

fever

N/V/D

mucositis

parotid swelling

61
Q

Long-term toxicities of TBI

A

Form cataracts

Growth retardation

Carcinogenesis

Reproductive sterility (not always)

Secondary malignancies

62
Q

Common conditioning regimen for ALL

A

Cy/TBI

63
Q

Common conditioning regimen for AML

A

BuCy

64
Q

Common conditioning regimen for lymphomas

A

BEAM

BEAC

65
Q

Common conditioning regimen for multiple myeloma

A

high dose melphalan

66
Q

How is HSCT given?

A

IV infusion

67
Q

What is the dose of cyclophosphamide in mobilization?

A

4 g/m2

68
Q

What is the dose of filgrastim in mobilization?

A

10 mcg/kg/day

round to nearest vial

69
Q

How many lifetime donations can an unrelated donor give in HSCT?

A

3

70
Q

Busulfan formulations

A

IV or Oral

71
Q

Who would you consider using reduced intensity conditioning regimen?

A

organ dysfunction

active infection

history of previous transplant

decreased performance status

exposure to chemo

72
Q

When do you use fludarabine continaing regimens?

A

Reduced intensity conditioning regimens in HSCT

73
Q

What is important to know about fludarabine containing regimens?

A

Immunosuppressive is critical!!

74
Q
A
75
Q

How does reduced intensity conditioning regimens work?

A
  • leukemia/lymphoma cells + receipients normals cells
  • get RIT therapy
  • Now have donor cells
  • Want chimerism: want donor cells to recognize and kill cancer cells
76
Q

Does allogeneic or autologous HSCT have a higher mortality rate?

A

Allogenic matched related

77
Q

What are the two types of graft failure?

A

primary

delayed (graft rejection)

78
Q

What are some causes of graft failure?

A

Immunologic reaction between host and donor

low number of stem cells infused

viral infections

drug reaction

79
Q

How to treat graft failure

A

CSF

Second infusion of stem cells

80
Q

When does mucositis occur after HSCT?

A

5 days post HSCT until WBC recovery

81
Q

T/F cryotherapy is effective for TBI

A

False!

Not effective

82
Q

T/F HSCT patients are not at risk of infections

A

false

Very high risk

83
Q

Risk of infection in HSCT is based on what?

A

Risk dependent on diagnosis

Length of neutropenia

Type of transplant

Prior history of infection

84
Q

When are you most concerned about SOS/VOD?

A

1st 30 days post transplant

85
Q
A
86
Q

When are you most concerned about HSV post HSCT?

A

1st 30 days

87
Q

When are you most concerned about Gram + infections post HSCT?

A

30-100 days

88
Q

When are you concerned about candida post HSCT?

A

1st 30 days

30-100 days

89
Q

What do you prophylax with during days 0-30 for a bacterial infection?

A

fluoroquinolone

90
Q

What do you prophylax with during day 0-30 for viral infection?

A

HSV: acyclovir

91
Q

What do you prophylax with during days 0-30 for funga infections post HSCT?

A

voricon, posacon, flucon

92
Q

When are you most concerned about PJP post HSCT?

A

day 30-100

93
Q

What do you prophylax with for PJP in HSCT?

A

bactrim or dapsone

94
Q

Pathophysiology of SOS/VOD

A

blood from central vein goes to portal vein thru sinusoids and sloughs off

Causes necrosis of endothelial lining leading to obstruction

*not a blood clot*

95
Q

Risk factors for SOS/VOD

A

TBI

busulfan

cyclophosphamide

liver dysfc prior to transplant

96
Q

Clinical presentation of SOS/VOD

A

Fluid retention

Sudden weight gain

RUQ ab tenderness

Increased bilirubin

97
Q

What do you prophylax with for SOS/VOD?

A

ursodiol 300 mg PO TID

98
Q

How can you treat SOS/VOD?

A

Supportive care

Defibrotide

99
Q

What is a major toxicity of defibrotide?

What is it used for?

A

Hemorrhage

Treatment of SOS/VOD

100
Q

When does acute GVHD occur?

What organs are involved?

A

<100 days

Skin, liver, GI tract

101
Q

When does chronic GVHD occur?

What organs are involved?

A

>100 days

multi-organ

102
Q

Pathophysiology of acute GVHD

A
  1. host cell damage leads to increase in inflammatory cytokine production
  2. donor T cell activation. Macrophage recruitment
  3. cytotoxic effector cells made and contribute to host cell injury
103
Q

Risk factors of acute GVHD

A

Degree of HLA match

Large # T lymphocytes in graft

Patient/donor age

Gender mismatch

104
Q

Risk factors for chronic GVHD

A

Degree of HLA match

History of acute GVHD

Patient age

Gender mismatch

PBSC source

105
Q

T/f prevention is better than treatment for GVHD

A

true

106
Q

How to prophylaxis for GVHD

A

Immunosuppression with chemo and post transplant

Combination prophylaxis

107
Q

What immunosuppresion agents do you give with conditioning chemo to prevent GVHD?

A

thymoglobulin (ATG) or alemtuzumab

108
Q

What immunosuppression agents do you give after transplant to prevent GVHD?

A

Cyclosporine/tacrolimus

With MTX or mycophenolate

109
Q

T/F you want to continue immunosuppression post HSCT

A

False!

Intention is to get off of it 6-12 months if no GVHD

110
Q

ADE of calcineurin inhibitors

A

Nephrotoxic

Electrolyte abnormalities

Seziures

Tremor

Nystagmus

HTN

Gingival hyperplasia

Hirsutism

Hyperglycemia

111
Q

When and who do you use post-transplant cyclophoamide in?

A

in HSCT

Only if haploidentical transplant!

112
Q

Skin GVHD

A

Rash: maculopapular, erythematous

Asymptomatic or pruritic and painful

Can lead to desquamation

113
Q

GI GVHD

A

Entire GI tract may be affected

N/V

Pain, water, secretory diarrhea

Bloody diarrhea and ileus may occur

114
Q

Liver GVHD

A

Labs may be only clue!

Elevated bili, AST/ALT, alkaline phosphatase

*Differential diagnosis is crtical*

Weight gain, pain or ascites rarely occur*

115
Q

How is acute GVHD graded?

What does 1-4 mean?

A

based on each organ system

1 is okay

2-4 bad

4 increases mortality

116
Q

How to treat acute GVHD

A

Corticosteroids

Grade I: topical

Grade 2-4: methylpred 2 mg/kg/day

117
Q

When treating acute GVHD what do you give if refractory to steroids?

A

more immunosuppression

118
Q

What options are there if refractory to steroids in acute GVHD?

A

Ruxolitinib

Mycophenolate mofetil

Sirolimus

119
Q

T/F acute GVHD resembles autoimmune disorders

A

false

chronic

120
Q

T/F chronic GVHD is a major cause of morbidity and mortality

A
121
Q

In chronic GVHD what are you most concerned about?

A

Pulmonary issues!

122
Q

What stage do you treat chronic GVHD?

A

moderate/severe

123
Q

How to treat chronic GVHD

A

Corticosteroids

Ruxolitinib

Ibrutinib

Oncology Exam 2 (5 decks)

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