Hematology pt 1 Flashcards
(130 cards)
1
Q
leukemia etiology
A
- unknown
- culmination of multiple processes resulting in genetic damage
2
Q
things that can cause leukemia
A
- radiation
- carcinogens (benzene)
- chemotherapy
3
Q
leukemia symptoms result from:
A
- bone marrow failure
- tissue infiltration
- circulating leukemia
4
Q
labs that indicate bone marrow failure when low
A
WBC (leukopenia)
RBC (anemia)
platelets (thrombocytopenia)
5
Q
technique to diagnose and stage leukemia
A
bone marrow aspiration and biopsy
6
Q
AML
A
acute myelogenous leukemia
7
Q
population AML is most common in
A
elderly
8
Q
regular intense induction therapy for AML
A
7 + 3
- 3 days of an anthracycline
- 7 days of cytarabine
9
Q
low intensity induction therapy for AML
A
azacitadine or decitabine
10
Q
consolidation therapy for AML
A
- HiDAC (high dose cytarabine) for all cytogenetics
- AlloHSCT can be used for intermediate or high risk cytogenetics
11
Q
salvage chemo for AML
A
- CLAG/CLAG-M (cladribine, cytarabine, GCSF +/- mitoxantrone)
- FLAG/FLAG-IDA (fludarabine + cytarabine + GCSF +/- idarubicin)
- MEC (mitoxantrone + etoposide + cytarabine)
12
Q
APL
A
acute promyleocytic leukemia
13
Q
APL etiology
A
fusion of chromosome 15 and 17 to form PML-RAR-alpha
14
Q
effects of PML-RAR alpha in APL
A
- binds to DNA and blocks transcription
- prevents differentiation
- fusion to retinoic acid receptor (RAR)
15
Q
APL induction treatment
A
-ATRA (all-trans retinoic acid) aka tretinoin given emergently -ATRA + ATO (arsenic trioxide) *curative*
16
Q
APL has high risk of what complication and how does it work
A
hemorrhage
annexin II produced in APL cells bind plasminogen and tPA to increase plasmin activity
17
Q
APL differentiation syndrome (retinoic acid syndrome) symptoms
A
- fever
- respiratory distress
- interstitial pulmonary infiltrates
- pleural or pericardial effusions
- weight gain
- hypotention
18
Q
how does APL differentiation syndrome lead to death
A
pleural effusion -> pulmonary infiltration -> pulmonary hemorrhage
19
Q
how to treat APL differentiation syndrome
A
dexamethasone
OR
prophylactic prednisone
20
Q
arsenic trioxide MoA
A
- low concentrations = differentiation inducer
- high concentrations = direct apoptosis inducer
21
Q
arsenic trioxide toxicities
A
- QT prolongation
- hepatotoxicity
22
Q
ALL
A
acute lymphoblastic leukemia
23
Q
where does ALL stem from
A
disorder of lymphoid progenitor cells
24
Q
ALL is most common in which patients
A
children
25
ALL subtypes
B cell
| T cell
26
ALL subtype with the better prognosis in adults
T cell
27
ALL prognosis in children
good, unless philadelphia chromosome is present
28
risk factors for ALL CNS relapse
- T cell ALL
- leukocytosis
- high risk cytogenetics
- presence of leukemic cells in CSF
29
Induction treatment for ALL
```
cortidosteroid
vincristine
anthracycline
+/- asparaginase
+/- BCR-ABL TKI
```
30
consolidation treatment for ALL
- continue chemo +/- TKI
| - allogeneic stem cell transplant if age <65 and no comorbidities
31
L-asparaginase mechnism
catalyzes hydrolysis of asparagine to aspartic acid which depletes resources for RNA and DNA synthesis, leading to apotosis
32
L-asparaginase adverse effects
PE
pancreatitis
thrombosis
hepatotoxicity
33
drugs for relapsed/refractory ALL
blinatumomab
| inotuzumab
34
blinatumomab MoA
bispecific T cell engager that binds both B and T cells at the same time
35
Inotuzumab MoA
binds to CD22 of B cells which allows for calicheamicin to induce double stranded breaks in the cell
36
CML
chronic myeloid leukemia
37
CML is most common in which patients
adult to elderly
38
CML is caused by what
bcr/abl philadelphia chromosome
39
phases of CML
chronic
accelerated
blast
40
chronic phase of CML features
- largely asymptomatic
- some splenomegaly and anemia
- lasts 3-5 years
- makes up 90% of new diagnoses
41
accelerated phase of CML features
- splenomegaly, anemia, bone/joint pain, fever
- lasts months
- cell maturation arrest
42
blast phase of CML features
- anemia, infections, bleeds
- duration is days to weeks
- presents as acute
43
treatment goal of CML
complete cytogenetic response in 1 year
44
treatment of CML
TKIs
| imatinib first line
45
most TKIs are inhibitors and substrates for what CYP
3A4
46
TKI with a BBW for vascular occlusion
ponatinib
47
discontinuation of TKI
its a trick
- guidelines recommend indefinite continuation in pts. with responsive disease
- this is to reduce relapse
48
treatment of CML accelerated phase
- imatinib
- dasatinib
- nilotinib
- omacetaxine
- allogeneic HSCT
49
CLL
chronic lymphocytic leukemia
50
CLL pathophysiology
clonal proliferation and accumulation of CD5 B cells in blood, bone marrow, lymph, and spleen
51
key genetic marker in CLL that indicates poor chemo response
Del 17p, most of which have P53 mutation
52
first line treatments for CLL with no del 17p present in pts <65
- fludarabine, cyclophosphamide, rituximab
| - bendamustine, rituximab
53
first line treatments for CLL with no del 17p present in pts >65 or comorbidities
- obinutuzumab + chlorambucil
| - ibrutinib
54
ibrutinib MoA
-covalently binds bruton tyrosine kinase to inhibit proliferation and survival of B cells
55
ibrutinib common side effects
n/d
fatigue
cough
56
ibrutinib and bleeding risk
- do not administer with warfarin
| - hold for 3-7 days before and after surgery
57
preferred treatment of relapsed CLL without del 17p present
ibrutinib
OR
idelalisib + rituximab
58
idelalisib MoA
- PI3K delta inhibitor
| - inhibits B cell and CSCR 4/5 signaling which prevents trafficking and homing of B cells to lymph and marrow
59
idelalisib adverse effects
hepatotoxicity
diarrhea/colitis
pneumonitis
infection
60
first line treatment for CLL with del 17p
-ibrutinib
-HDMP + R
others
61
treatment for relapsed/refractory CLL with del 17p
ibrutinib
venetoclax
idelalisib + R
others
62
venetoclax MoA
targets BCL-2 in order to help restore the process of apoptosis
63
venetoclax indication
CLL relapsed/refractory with del 17p present
64
two types of bone marrow transplant
allogeneic
| autologous
65
type of BMT that has problems with graft vs. host
allogeneic
66
complications seen after stem cell transplant
infection
GVHD
pulmonary complications
67
autologous stem cell source
the patient
68
phases of SCT
- conditioning/ preparative from day-7 to day-3
- transplatation day 0
- post transplant
69
engraftment
when transplanted cells start to grow
70
acute GVHD features
- occurs before day +100
| - affects skin, GI tract, liver
71
chronic GVHD features
- occurs after day +100
| - affects all organ systems
72
GVHD prophylaxis is given to who
all allogeneic recipients
73
GVHD prophylaxis drugs
immunosuppressants
- cyclosporine/tacro + methotrexate
- cyclosporine/tacro + mycophenolate
- sirolimus + tacrolimus
74
vaccines that are contraindicated in pts with SCT
MMR
varicella
*live ones*
75
structures in the lymphatic system
- bone marrow
- lymph nodes
- spleen
- thymus
- tonsils
- MALT
76
bone marrow lymphocytes are primarily what type
b cells
77
role of b cells
- produce antibodies
| - mature into memory b cells
78
types of t cells
cytotoxic CD8
| helper CD4
79
role of cytotoxic CD8 cells
recognize infected cell membranes and destroy them
80
role of helper t CD4 cells
release cytokines that attract other WBCs
81
role of Natural killer cells
recognize foreign or infected cells via MHC 1
82
what is lymphoma
blood cancer that begins in the lymph node
83
pathophysiology of hodgkins lymphomas
malignant Reed-Sternberg cells recruit more cells
84
Reed-Sternberg cell features
large
bi-nucleated
express CD30 and CD15
85
risk factors for hodgkin lymphoma
* not well defined*
- same sex siblings as HL pt. have greater risk
- many tumors have Epstein-Barr virus
- previous solid organ transplant
- HIV
86
signs and symptoms of hodgkin lymphoma
- painless rubbery mass, most often in neck
- fever
- drenching night sweats
- often times asymptomatic
87
lymphoma age distribution for hodgkins lymphoma
bimodial
peak in 20-30s then again over 50
-death more common in older patients
88
diagnosis and work up of HL
- biopsy
- chest Xray
- CT
- PET scan *most important*
89
staging of HL
- stage 1 = single node region or structure
- stage 2 = two or more nodes regions on same side of diaphragm
- stage 3 = lymph nodes regions on both sides of diaphragm
- stage 4 = diffuse or disseminated involvement
90
factors used in the International Prognostic Score for advanced stage HL
- albumin < 4
- hemoglobin <10.5
- male
- stage 4
- age >45
- WBC >15000
- lymphopenia <600
91
treatment modalities for HL
radiation
chemo
surgery
autologous SCT
92
HL cure rate
81%
93
chemo regimens for acute HL
MOPP
| ABVD
94
MOPP regimen drugs
```
mechlorethamine
vincristine (oncovin)
procarbazine
prednisone
-28 day cycle
```
95
problem with MOPP
lots of secondary leukemias occur
96
ABVD regimen drugs
```
doxorubicin (adriamycin)
bleomycin
vinblastine
dacarbazine
-28 day cycle
```
97
acute toxicities of ABVD and MOPP
N/V
myelosuppression
anemia
mucositis/stomatitis
98
long term toxicities of ABVD and MOPP
- secondary malignancies (MOPP)
- pulmonary fibrosis - bleo
- CHF - doxorubicin
- gonadal dysfunction/sterility (MOPP)
99
treatment for favorable early stage HL
ABVD for 2-4 cycles + involved field RT
100
treatment for unfavorable early stage HL
ABVD for 4-6 cycles +/- RT
101
indicators of unfavorable early stage HL
b symptoms
bulky disease
extra nodal or >3 sites
102
treatment for advanced stage HL
ABVD for 6 cycles
| escalated BEACOPP for unfavorable
103
escalated BEACOPP regimen
```
bleomycin
etoposide
doxorubicin (adriamycin)
cyclophosphamide
vincristine (oncovin)
procarbazine
prednisone
*21 day*
```
104
brentuximab vedotin MoA
- targets CD30
| - carries MMAE which potentially disrupts microtubule polymerization
105
brentuximab side effects
peripheral neuropathy
| neutropenia
106
risk factors for non hodgkins lymphoma
- older people
- Hx of lymphoma
- exposure to radiation, pesticides
- immuno-suppressants
- lupus, RA
- HIV
- epstein-barr
- hep C
107
clinical presentation of non hodgkins lymphoma
- lymphadenopathy
| - B symptoms (fever, night sweats)
108
NHL diagnosis
- biopsy
- molecular tests
- cell surface markers
- cytogenetics (C. 14)
109
NHL staging
same as HL, but does not work as well because spread is not contiguous
110
prognostic index for NHL
- age >60
- serum LDH >normal
- performance status 2-4
- stage 3 or 4
- extranodal involvement
111
main indolent NHL example
follicular lymphoma
112
aggressive NHL type
diffuse large b-cell lymphoma
113
highly aggressive NHL type
burkitt lymphoma
114
indolent NHL definition
- survival of untreated disease is measured in years
| - waxing and waning of lymph nodes is commonly seen
115
aggressive NHL definition
survival of untreated disease is measured in months
116
highly aggressive NHL definition
survival of untreated disease is measure din weeks
117
treatment for indolent NHL
-watch and wait b/c its slow growing
-single-agent chemo
o chlorambucil
o cyclophosphamide
o fludarabine
-immunotherapy - rituximab
-chemo-immuno combo - R-CHOP
-targeted - ibrutinib
118
treatment for aggressive NHL
R-CHOP
DA-R-EPOCH
-CODOX-M
119
R-CHOP drugs
```
Rituximab
Cyclophosphamide
Hydroxydaunorubicin (doxorubicin)
Oncovin (vincristine)
Prednisone
```
120
rituximab adverse reactions
fever
chills
rigors
*push through these because they really only show in the first cycle or two
121
rituximab requires what pre-medication
tylenol
diphenhydramine
ranitidine
122
rituximab MoA
causes apoptosis by:
- recruiting NK cells
- activating compliment cytotoxicity
- apoptosis via calcium influx
123
cyclophosphamide adverse effects
SIADH
- hemorrhagic cystitis
- pulmonary tox
- alopecia
124
cyclophosphamide MoA
alkylator
| forms covalent bonds at N7 of quanine
125
doxorubicin MoA
topo II inhibitor
126
vincristine MoA
microtubule stabilization
127
NHL type with best chance for cure
aggressive
128
treatments for NHL relapse after autologous BMT
ICE
DHAP
GemOx
Yescarta
129
treatment for highly aggressive NHL
R-CODOX-M/IVAC
DA-R-EPOCH
*R-CHOP is not adequate*
130
which lymphoma is harder to cure
NHL
