HSCT Flashcards
(122 cards)
1
Q
What are autologous donors?
A
From self or twin (synergeneic)
2
Q
What are allogeneic donors?
A
From compatible donor
3
Q
What are other terms for HSCT?
A
Bone marrow transplantation (BMT)
Stem cell transplantation (SCT)
4
Q
What is the rationale of using autologous HSCT?
A
To facilitate the ability to deliver HD chemotherapy
5
Q
What is autologous HSCT known as?
A
HD chemotherapy with stem cell “rescue”
6
Q
What type of toxicity is dose limiting for autologous HSCT?
A
Non-hematopoietic organ toxicity
7
Q
Which diseases are autologous HSCT used?
A
Lymphomas
Multiple myeloma
Relapsed testicular and germ cell cancers
8
Q
What is the rationale for allogeneic HSCT?
A
Delivery of HD chemotherapy (with rescue)
Immune reconstitution and graft mediated antitumor activity
9
Q
What conditions are allogeneic HSCT used to treat?
A
Acute leukemias
CML
Immune deficiency states
Other hematologic disorders
10
Q
What marker is used to choose donors?
A
HLA
11
Q
How many HLA antigens are used for matching and what is the gold standard?
A
10
10/10 matching
12
Q
What type of donor is the gold standard?
A
Matched related sibling donor (MRD)
13
Q
What is a haploidentical HSCT?
A
HLA “half-math” donor
Donor is parent/child
14
Q
What type of prophylaxis is required with alloreactive T-cell depleting post transplant cyclophosphamide?
A
Graft-versus-host prophylaxis
15
Q
What volume is required for a stem cell transplantation?
A
Requires 2-6 x 10^6 stem cells/kg body wt
16
Q
What are sources of stem cells?
A
Bone marrow (BM) Peripheral blood stem cells (PBSC) Umbilical cord (UC)
17
Q
Does BM or PBSC have a faster engraftment?
A
PBSCT
18
Q
Does BM or PBSC need more transfusion support?
A
BM
19
Q
Does BM or PBSC have early regimen related complications?
A
BM
20
Q
Does BM or PBSC have a shorter duration of hospitalization?
A
PBSC
21
Q
Does BM or PBSC have an increased number of stem cells collected?
A
PBSC
22
Q
Does BM or PBSC have an increased number of T cells collected?
A
10-fold PBSC
23
Q
Does BM or PBSC have an increased risk of chronic GVHD?
A
PBSC
24
Q
Does BM or PBSC have an increased risk of acute GVHD?
A
Similar across both
25
What are the advantages for umbilical cord blood?
Large number of stem cells
Greater HLA disparity acceptable
Decreased risk GVHD
26
What are the disadvantages of umbilical cord blood?
Wt limit (<60 kg)
Delayed engraftment
Engraftment failure
27
What is the mobilization/collection of stem cells?
Process by which stem cells are forced into peripheral blood and collected
28
Where can stem cells be collected from?
Direct bone marrow aspiration
| Mobilization and peripheral blood apheresis
29
What does mobilization refer to?
Method used to enrich the content of stem cells in the peripheral bleed
30
What are the 3 methods of mobilization?
G-CSF
Plerixafor + G-CSF
Chemomobilization (chemo + G-CSF)
31
Which type of donor is chemomobilization never used in?
Allogeneic donors
32
What agents are used in G-CSF mobilization?
Filgrastim
33
What are the pros of GCSF mobilization?
Well tolerated
34
What are the SEs of G-CSF?
Bone pain
Fever
General malaise
35
What agents are used with chemomobilization?
Etoposide/cyclophosphamide
| G-CSF
36
What are the pros of chemomobilization?
More rapid mobilization
| Fewer apheresis sessions
37
What are the cons of chemomobilization?
Risks of chemo
| Febrile neutropenia
38
What agent is used with Plerixafor + GCSF mobilization?
CXCR4 antagonist
39
What are the SEs of CXCR4 antagonists?
N/D
40
What is the purpose of conditioning regimens?
Myelosuppressive/myeloablative
| Immunosuppressive
41
Which type of donor requires an immunosuppressive conditioning regimen?
Allogeneic
42
How is myelosuppressive/myeloablative conditioning done?
Make room in the marrow space for infused stem cells to settle and propagate
43
Which type of conditioning regimen is required for autologous and allogeneic SCT?
Myelosuppressive/myeloablative
44
What is the major type of antitumor agents used in conditioning chemotherapy?
Alkylating agents
Busulfan
Cyclophosphamide
Melphalan
45
What are busulfan's dose limiting toxicities?
Hepatotoxicity
| Mucositis
46
What are carboplatin's dose limiting toxicities?
Hepatic/renal toxicity
Mucositis
Peripheral neuropathy
47
What are carmustine's dose limiting toxicities?
Pulmonary
48
What are cyclophosphamide's dose limiting toxicities?
Cardiac
49
What are cytarabine's dose limiting toxicities?
Neurotoxicity (cerebellar)
50
What are etoposide's dose limiting toxicities?
Mucositis
51
What are fludarabine's dose limiting toxicities?
Neurotoxicity
52
What are ifosfamide's dose limiting toxicities?
Renal
| Neurotoxicity
53
What are melphalan's dose limiting toxicities?
Mucositis
54
What are thiotepa's dose limiting toxicities?
Mucositis
| Neurotoxicity
55
Which conditioning regimen is irreversible w/o SC support?
Myeloablative
56
Which conditioning regimen should always be given with SC support?
Reduced intensity conditioning
57
Which conditioning regimen has an anti-tumor effect based on the graft-vs-tumor effect?
Non-myeloablative
58
What are acute toxicities of HSCT?
Alopecia
Myelosuppression
N/V
GI mucositis
59
What are the common conditioning regimens for autologous HSCT?
Melphalan single agent
BEAM (Carmustine, Etoposide, Cytarabine, Malphalan)
Busulfan/ Cyclophsophamide/ Etoposide
60
To what degree of myelosuppression does autologous HSCT cause?
Complete myelosuppression, no immunosuppression needed
61
To what degree of myelosuppression does allogeneic HSCT cause?
Varying degrees of myelosuppresson and immunosuppression
62
What are the common conditioning regimens for allogeneic HSCT?
Fludarabine/ cyclophosphamide/ TBI*
TBI/ cyclophosphamide
Busulfan/ Melphalan
Busulfan/ fludarabine/ ATG
63
What are the advantages of total body irradiation?
Active against a variety of malignancies (chemoresistant as well)
Immunosuppressive effects
Penetrates sanctuary sites (CNS and testes)
64
What is the initial standard combination for total body irradiation?
MA with Cy
65
What are the toxicities of total body irradiation?
DLT = pulmonary, hepatic, GI
| Long term = decreased growth development, pulmonary insufficiency, cataracts, secondary malignancies
66
What is engraftment?
Normalization of all peripheral blood counts (WBC< plt, HgB)
67
When does ANC recovery typically accur?
14-21 days
68
When does plt transfusion independence typically occur?
Before day 35
69
Does engraftment indicate cure/remission?
No
70
What is a graft failure?
Inadequate hematopoietic function after stem cell transplantation
71
What is primary graft failure?
Failure to achieve engraftment by expected time
72
What is secondary graft failure?
Failure to maintain graft after initial engraftment
73
What is the treatment for graft failures?
Re-collect donor for second infusion
| Modification of immunosuppression to allow graft to grow
74
In the first 30 days post transplant, what infection has a big risk and how do we treat it??
Candida - fluconazole
75
For days 30-100, which fungus do we worry about?
Aspergillus spp
76
How do we treat aspergillus?
Voriconazole
Posaconazole
Ampho B
77
How do we diagnose aspergillius?
Serum GM
CT findings
Bronchoalveolar lavage (aspiration and biopsy)
78
In days 0-30, which virus are we worried about reactivation?
HSV
79
In days 30-100, what viral infections are we worried about and how do we pre-empt it?
CMV
| Ganciclovir
80
For autologous transplants, when do we discontinue fluconazole prophylaxis?
ANC > 500
81
What viral infection are we concerned about after 100 days?
VSV
82
What bacterial infection are we concerned about after 100 days?
Pneumocytis Carinii pneumonia (PCP)
83
What fungal infections are we concerned about after 100 days?
```
Mould
Rare fungi (fusarium, zygomycetes)
```
84
What is acute GVHD?
Mediated by mature T cells in infused graft
85
When does acute GVHD typically occur?
Within 100 days
86
What is chronic GVHD?
Mediated by developing T cells
| Host thymus is unable to educate maturing donor T cells to not react to self
87
When does chronic GVHD typically occur?
100+ days
88
Is acute or chronic GVHD the major source of morbidity and mortality following allogeneic SCT?
Acute
89
What organs are typicaly affected in acute GVHD?
Skin
Gut
Liver
(in this order)
90
How do we grade acute GVHD?
Based on extent of manifestations in each of the 3 major target organs
91
How do we stage acute GVHD?
Based on composite of grading in each organ system and extent of functional impairment
92
What are the most common organs affected in chronic GVHD?
Skin
| Liver
93
How is chronic GVHD characterized?
Sclerosis, contracture of the skin
94
How is chronic GVHD graded?
Limited or extensive
95
What is considered limited chronic GVHD?
Skin and liver w/o sclerosis
96
What is considered extensive GVHD?
Skin sclerosis or involvement of sites outside of skin and liver
Eye, mouth, lungs, GI tract, peripheral nervous system, marrow, vaginal tract involvement
97
What types of medications can be used to prevent GVHD?
```
Calcineurin inhibitors
M-TOR inhibitors
Inhibitors that block cell growth
Inhibitors that affect salvage of purine nucleotides
Agents that remove T lymphocytes in vivo
```
98
What are calcineurin inhibitors?
Tacrolimus
| Cyclopsorine
99
How do calcineurin inhibitors work?
Inhibit T cell activation
100
What are the M-TOR inhibitors?
Rapamycin
101
How do M-TOR inhibitors work?
Inhibition of progression through cell cycle
102
What are inhibitors that block cell growth?
MTX
| Cyclophsophamide
103
What are agents that remove T lymphocytes in vivo?
Alemtuzumab
| Anti-thymocyte globulin
104
What are the prophylaxis treatments of GVHD?
Cyclophosphamide
| Tacrolimus + mycophenolate
105
What are tacrolimus toxicities?
Tremor
HA
Electrolyte abnormalities
Nephrotoxicity
106
What are mycophenolate mofetil toxicities?
GI toxicity
Infections (BBW)
Pure red cell aplasia
107
Which prophylaxis medication for GVHD is teratogenic?
Mycophenolate mofetil
108
What are the toxicities of cyclophosphamide?
Hemorrhagic cystitis
| Cardiogenic shock
109
What are post transplant cyclophosphamide's CPs?
Empiric diuresis to make net negative on D+2, aggressive diuresis during high IV fluids rate
110
What is the mainstay of therapy for acute GVHD?
Corticosteroids
111
What is the antifungal used during corticosteroid use for acute GVHD?
Posaconazole
112
What is the treatment of chronic GVHD?
Corticosteroids
Rituximab
PUVA/narrow band UVB therapy
Pentostatin
113
What is sinusoidal obstruction syndrome?
Obstructive liver disease due to microthrombi in liver sinusoids
114
What causes sinusoidal obstruction syndrome?
Damage to hepatic sinusoids and hepatocytes leads to obstruction of sinusoidal flow
115
What are clinical presentations of sinusoidal obstruction syndrome?
Fluid retention
Jaundice
Hepatomegaly
Weight gain
116
What are the RFs for sinusoidal obstruction syndrome?
TBI, busulfan, or cyclophosphamide containing conditioning regimens
Pre-existing liver dysfunction
Pre-transplant exposure to liver toxins such as gemtuzumab
117
When does sinusoidal obstruction syndrome typically present?
W/in 3 weeks of SCT
118
What is the clinical diagnosis of sinusoidal obstruction syndrome?
Wt gain
Hyperbilirubinemia
Ascites
119
What are the preventative measures for sinusoidal obstruction syndrome?
Busulfan PK monitoring
Ursodiol
Heparin
120
What is the treatment of sinusoidal obstruction syndrome?
Defibrotide - if evidence of renal or pulmonary disfunction
121
What do we monitor for with defibrotide?
bleeding
122
What is the treatment of diffuse alveolar hemorrhage?
HD steroids
