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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
Which disease states do you use allogeneic stem cell transplant?
Acute leukemia Severe aplastic anemia Sickle cell anemia metabolic disorders- peds SCID
26
Describe the timing of HSCT if you have high risk disease
1. diagnosis 2. chemo 3. remission 4. HSCT
27
Describe the timing of HSCT if you have a lower risk of disease
1. diagnosis 2. chemo 3. remission 3. wait and watch
28
T/F if you have SCID or metabolic disorders you can have HSCt before chemo
True!
29
What are the 3 phases of stem cell transplant?
Stem cell collection Transplant Post transplant
30
What 3 sites can you collect stem cells from?
peripheral blood bone marrow umbilical
31
What is the surrogate marker for stem cell collection?
CD34 antigen
32
Why do we care about the number of cells the recipient has prior to transplant?
correlated with recovery!
33
What is the minimum number of cells of the recipient prior to HSCT?
2 x 106 cells/kg
34
What is the target number of cells in the recipient prior to HSCT?
5 x 106 cells/kg
35
What is the main advantage of using stem cells from the bone marrow?
Decreased risk of chronic GVHD
36
Describe using stem cells from bone marrow
- general anesthesia - takes 1-2 hours - multiple aspirations from iliac crests: PAINFUL - Large volume needed - given to recipient after harvest - longer time to engraft
37
What are some advantages of using stem cells from the peripheral blood?
- no general anesthesia - small volume needed - rapid engraftment
38
Describe using stem cells from the peripheral blood
- utilize mobilization techniques prior to harvest - collection may be 3-5 hours per day - may need multiple days
39
Which source of stem cells is preferred for autologou transplants and for most allogeneic transplants?
Peripheral blood
40
T/F using stem cells from the peripheral blood has a 2x higher risk of chronic GVHD
True
41
What does stem cell mobilization do? What do you use?
Stimulates stem cell production Use chemo, growth factors or both!
42
Who do you need to mobilize stem cells in?
Peripheral blood stem cell collection
43
What growth factors can be used in mobilization regimen of HSCT?
Filgrastim Sargramostim
44
What is the most common chemo agent used in mobilization regimens for HSCT?
cyclophosphamide
45
When using filgrastim for mobilization, what side effects do you need to warn the patient about?
bone pain: try claritin splenic enlargement: no vigorous activity
46
What factors influence mobilization?
- 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
47
What drug inhibits the chemokine receptors that act as anchors stem cells to the marrow?
Plerixafor (Mozobil)
48
Who would you use plerixafor (Mozobil) in?
- failed prior mobilization attempt - few PBSC after 3 days of GCSF
49
T/F when using plerixafor you do not continue using growth factors
False! Continue morning growth factor doses!
50
Toxicity of plerixafor
Diarrhea Nausea Injection site reactions
51
Toxicity of growth factors
Bone pain Fever Injection site pain/reactions Splenic enlargement
52
Main toxicity of cyclophosphamide
Hemorrhagic cystitis N/V
53
What are some advantages of using stem cells from umbilical cord?
- less stringent HLA requirements - decreased severe GVHD - decreased viral contamination - no risk to donor - product available immediately
54
What are some disadvantages of using stem cells from umbilical cord?
- limited number of cells - longer to engraft - no second donation - higher risk of graft failure
55
When are conditioning regimens done in HSCT?
immediately before transplant
56
What are the goals of conditioning regimens?
- Kill as many tumor cells as possible: autologous, allogeneic - Immunosuppression to prevent GVHD: allogeneic
57
What makes up a conditioning regimen?
chemo +/- total body irradiation (TBI)
58
T/F patients must be healthy prior to HSCT to have myeloablative conditioning regimens
True!
59
Main toxicities of melphalan
Mucositis GI toxicity
60
Acute toxicities of TBI
fever N/V/D mucositis parotid swelling
61
Long-term toxicities of TBI
Form cataracts Growth retardation Carcinogenesis Reproductive sterility (not always) Secondary malignancies
62
Common conditioning regimen for ALL
Cy/TBI
63
Common conditioning regimen for AML
BuCy
64
Common conditioning regimen for lymphomas
BEAM BEAC
65
Common conditioning regimen for multiple myeloma
high dose melphalan
66
How is HSCT given?
IV infusion
67
What is the dose of cyclophosphamide in mobilization?
4 g/m2
68
What is the dose of filgrastim in mobilization?
10 mcg/kg/day round to nearest vial
69
How many lifetime donations can an unrelated donor give in HSCT?
3
70
Busulfan formulations
IV or Oral
71
Who would you consider using reduced intensity conditioning regimen?
organ dysfunction active infection history of previous transplant decreased performance status exposure to chemo
72
When do you use fludarabine continaing regimens?
Reduced intensity conditioning regimens in HSCT
73
What is important to know about fludarabine containing regimens?
Immunosuppressive is critical!!
74
75
How does reduced intensity conditioning regimens work?
- 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
Does allogeneic or autologous HSCT have a higher mortality rate?
Allogenic matched related
77
What are the two types of graft failure?
primary delayed (graft rejection)
78
What are some causes of graft failure?
Immunologic reaction between host and donor low number of stem cells infused viral infections drug reaction
79
How to treat graft failure
CSF Second infusion of stem cells
80
When does mucositis occur after HSCT?
5 days post HSCT until WBC recovery
81
T/F cryotherapy is effective for TBI
False! Not effective
82
T/F HSCT patients are not at risk of infections
false Very high risk
83
Risk of infection in HSCT is based on what?
Risk dependent on diagnosis Length of neutropenia Type of transplant Prior history of infection
84
When are you most concerned about SOS/VOD?
1st 30 days post transplant
85
86
When are you most concerned about HSV post HSCT?
1st 30 days
87
When are you most concerned about Gram + infections post HSCT?
30-100 days
88
When are you concerned about candida post HSCT?
1st 30 days 30-100 days
89
What do you prophylax with during days 0-30 for a bacterial infection?
fluoroquinolone
90
What do you prophylax with during day 0-30 for viral infection?
HSV: acyclovir
91
What do you prophylax with during days 0-30 for funga infections post HSCT?
voricon, posacon, flucon
92
When are you most concerned about PJP post HSCT?
day 30-100
93
What do you prophylax with for PJP in HSCT?
bactrim or dapsone
94
Pathophysiology of SOS/VOD
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
Risk factors for SOS/VOD
TBI busulfan cyclophosphamide liver dysfc prior to transplant
96
Clinical presentation of SOS/VOD
Fluid retention Sudden weight gain RUQ ab tenderness Increased bilirubin
97
What do you prophylax with for SOS/VOD?
ursodiol 300 mg PO TID
98
How can you treat SOS/VOD?
Supportive care Defibrotide
99
What is a major toxicity of defibrotide? What is it used for?
Hemorrhage Treatment of SOS/VOD
100
When does acute GVHD occur? What organs are involved?
\<100 days Skin, liver, GI tract
101
When does chronic GVHD occur? What organs are involved?
\>100 days multi-organ
102
Pathophysiology of acute GVHD
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
Risk factors of acute GVHD
Degree of HLA match Large # T lymphocytes in graft Patient/donor age Gender mismatch
104
Risk factors for chronic GVHD
Degree of HLA match History of acute GVHD Patient age Gender mismatch PBSC source
105
T/f prevention is better than treatment for GVHD
true
106
How to prophylaxis for GVHD
Immunosuppression with chemo and post transplant Combination prophylaxis
107
What immunosuppresion agents do you give with conditioning chemo to prevent GVHD?
thymoglobulin (ATG) or alemtuzumab
108
What immunosuppression agents do you give after transplant to prevent GVHD?
Cyclosporine/tacrolimus With MTX or mycophenolate
109
T/F you want to continue immunosuppression post HSCT
False! Intention is to get off of it 6-12 months if no GVHD
110
ADE of calcineurin inhibitors
Nephrotoxic Electrolyte abnormalities Seziures Tremor Nystagmus HTN Gingival hyperplasia Hirsutism Hyperglycemia
111
When and who do you use post-transplant cyclophoamide in?
in HSCT Only if haploidentical transplant!
112
Skin GVHD
Rash: maculopapular, erythematous Asymptomatic or pruritic and painful Can lead to desquamation
113
GI GVHD
Entire GI tract may be affected N/V Pain, water, secretory diarrhea Bloody diarrhea and ileus may occur
114
Liver GVHD
Labs may be only clue! Elevated bili, AST/ALT, alkaline phosphatase \*Differential diagnosis is crtical\* Weight gain, pain or ascites rarely occur\*
115
How is acute GVHD graded? What does 1-4 mean?
based on each organ system 1 is okay 2-4 bad 4 increases mortality
116
How to treat acute GVHD
Corticosteroids Grade I: topical **Grade 2-4: methylpred 2 mg/kg/day**
117
When treating acute GVHD what do you give if refractory to steroids?
more immunosuppression
118
What options are there if refractory to steroids in acute GVHD?
Ruxolitinib Mycophenolate mofetil Sirolimus
119
T/F acute GVHD resembles autoimmune disorders
false chronic
120
T/F chronic GVHD is a major cause of morbidity and mortality
121
In chronic GVHD what are you most concerned about?
Pulmonary issues!
122
What stage do you treat chronic GVHD?
moderate/severe
123
How to treat chronic GVHD
Corticosteroids Ruxolitinib Ibrutinib

Oncology Exam 2 (5 decks)

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