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Sweatman Hematologic Malignancies Flashcards

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1
Q

What are we trying to achieve with Heme. Malignancy drugs

A

myelosuppresson–> an unwanted side effect usually but here it is the desired effect

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2
Q

Consequence of myelosupression

A

opportunistic infection risk goes up considerable

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3
Q

Induction

A

high dose: intolerable chronically

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4
Q

Consolidation

A

repetition of induction therapy during remission: intolerable chronically–>increases chance of eradication

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5
Q

Maintainence

A

long term tolerable, lower dose therapy during remission

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6
Q

Adjuvant

A

after sx/ radiotherapy

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7
Q

neo-adjuvant

A

before sx/ radiotherapy

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8
Q

Metronomic dosing used for

A

multiple myeloma, recurrent NHL, malignant glioma, glioblastoma, SCC, breat, ovarian, and hormone resistant prostate cancer
*but not all tumor types in all pt.’s

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9
Q

Metronimic therapy work by

A

direct and indirect effect on the tumor cells and their
microenvironment
–>takes into account darwinian selection (chemotherapy we are applying)

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10
Q

how can metronomic dosing affect a tumor

A

> inhibit angiogenesis
stimulate anti cancer immune response
create a drug-driven dependency/deprivation effect

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11
Q

explains phenotypic divergence arising from applied chemo and the coinciding resistance

A

adaptive therapy

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12
Q

explain adaptive chemotherapy treatment

control vs eradication

A

takes into account resistant vs non-resistance clones and tries to maintain an acceptable amount of these (retain the correct ration)–> overall goal is to control the tumor, maintain some level of resistant/non-resistance–>bring the number down chronically rather than acutely

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13
Q

most common toxc effects of metronomic dosing

A

N/V, Grade 1 and anemia, neutropenia, leukopenia, and pymphopenia

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14
Q

more than half the leukemias present

A

acutely

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15
Q

Most common in children 3-7

A

ALL

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16
Q

Most commonly seen in elderly

A

CLL

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17
Q

Ph1 chromosome most commonly seen in (3)

A

CML (210)> ALL(190)>AML

*detectable by FISH or PCR

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18
Q

AML tx regimine

INDUCTION

A

CDT–
Cytarabine (Ara-C)
Daunorubicin
Thioguanine, 6-TG

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19
Q

MOA for Daunorubicin

A

free radical producer
intercolater
topo II inhibitor

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20
Q

Cytarabine MOA

A

pyrimidine antimetabolite

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21
Q

Thioguanine MOA

A

purine antimetabolite

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22
Q

Daunorubicin class

A

anthracycline

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23
Q

Side effect of Daunorubicin

A

cardiac toxicity and arrhythmia

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24
Q

Side effects of AML induction regimine

A

all are myelosupressors–> opportunistic infection

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25
Post remission therapy for AML
cytarabine and HSCT
26
APML
ATRA + Dunorubicin or Idarabine + cytarabine
27
class of atra
retinoid drug
28
retinoic acid syndrome | side effect of ATRA
fever, SOB, weight GAIN, pulmonary infiltrates, and pleural/pericardial effusions
29
other tx for PML-RARa fusion gene found in PML
Arsenic
30
Arsenic trioxide MOA
causes proteolysis of the PML-RARa fusion protein--> allows myelocytes to differentiate and not proliferate
31
Warnings with ARSENIC trioxide
BLACK BOX warning involving CV | -AV block, QT prolong, electrolyte imbalance
32
are CV effects seen with ATRA
NO
33
SIde effect seen wit Arsenic other than CV
differntiation syndrome
34
define differentiation syndrome
fever, SOB, weight GAIN, pulmonary infiltrates, pleural/pericardial effusions AND leukocytosis
35
ALL tx regimine (general)
prednisone + vincristone + anthracycline + asparaginase
36
List the drugs aproved for tx of ALL 60-80% response in adults
``` pegasperaginase doxorubicin prednisone imatinib vincristine daunorubicin methotrexate ```
37
how do you treat a BCR-ABL kinase tumor
imatinib always | response in 90% of adults
38
how to you accomplish CNS prophylaxis with ALL tx
IT methotrexate and systemic methotrxate
39
Consolidation therapy for ALL
methotrexate and mercaptopurine
40
ASPARAGINASE moa
enzyme that degrades asparagine--> cell cannot make proteins without this amino acid --
41
why pegylate
extends duration and increase activity in the body
42
whe to use imatinib
chronic phase of myeloid leukemia
43
first line tx of CML
imatinib
44
CML drugs
``` imatinib nilotinibi dasatinib cytarabine Interferon alfa-2a ```
45
imatinib, nioltinib and dasatinib are all
tyrosine kinase inhibitors that bind to a highly conserved ATP binding site on the tk *only consitent curatie tx for CML
46
resitance mechanism to TKI
mutations in the thymine gate T3151 T6701 etc
47
Tx for CLL
Fludarabine Cyclophosphamide Rituximab and diff combinations of these 3
48
rituximab class
MAB that targets CD20 on B cells | *compliment dep and ADCC cell death
49
fludarabine class
antimetabolite
50
cyclophosphamide
alkylating agent
51
Fludarabine comlication
worsens Autoimmune hemolytic anemia | (obv drug induced) tx is with corticosteroids
52
hyperurcemia tx
allopurinol and hydration
53
bendamustine
antimetabolite and an alkylating agent result in DNA ds break, activate p53 and inhibits mitotic check point--> cells enter cycle wiht DNA damage and apoptosis happens
54
Hairy cell leukemia
Cladribine | Pentostain--> both antimetabs and interferon alfa2a
55
Hodgkin Lymphoma
ABVD
56
ABVD therapy
doxorubicin, belomycin, vinblastine, dacarabazine
57
CHOP
cyclophosphamide, doxorubicin, vincristine, prednisone +/- prednisone
58
HL tx gernarlities
anthracylin, carbazine, alkylating agent, mitotic spindle inhibitor
59
recurrence of HL
autologous stem cell transplant | *second chemo regimine not likley to work
60
high or low cure rate with HL
high but refractory disase is usally lethal
61
NHL tx | low stage disease
COMP | methotrxate + prednisone for 6 months
62
High stage B cell NHL | DLBC and Burkitt's
R-CHOP* rituximab + doxorubicin, cyclophosphamide, vincristine and prednisone
63
diff bw how we can trrat HL vs NHL
NHL will usualy epress CD20 therefore rituximab is an option
64
recurrent NHL tx
high dose therapy and SCT
65
Adverse effects of NHL tx
MDS and AML due to alkylating agents sterility, secondary malignancy (brain lung, kidney), LV dysfunciton, MDS and AML
66
MABs with radioactivity to CD 20
tositumomab (I131) ibritumomab (Y90) apoptosis, phagoctyosis, radionuclide damage *no binding in lymphoid tissue
67
side effects of radionuclide therapy
myelosupression (thrombocytopenia, neutropenia, anemia) | N/V, fever, chills
68
Burkitt's Tx CYLCLICAL
cyclophosphamide (alkylating agent) vincristine + doxorubicin cytarabine (ara-c)
69
Burkitts has a close association with which virus
EBV
70
Why intracethcal chemo is used in Tx. of Burkitt's
to ensure CNS coverage
71
ALL tx
prednisone, vincristine, asparaginase plus intracathecal methotrexate
72
AML TX
CYTARABINE, IDRUBACIN OR DAUNORUBICIN
73
BURKITT'S TX
cyclophosphamide and methotrexate, vincristine and doxorubicine, possible add cytarabine
74
CML tx
imatinib, newer TKI's interferon alfa2a
75
CLL tx
fludarabine + cyclophosphamide and or rituximab
76
Hairy Cell Leukemia tx
Cladaribine, Interferon, pentostatin
77
Hodgkins tx
ABVD+ prednisone | anthracyclin, bleomycin, vincristin, dacarbazine
78
NHL tx
CHOP or R-CHOP | cyclophosphamide, doxorubicin, vincristine and prednison + rituximab)
79
APML
atra, arsenic, idarubicin
80
Cytarabine MOA
bio-activated ARACTP inhibits DNA polymerase
81
Dacarbazine moa
DNA methylator
82
Arsenic and ATRA MOA
degrade PML-RARa
83
ASPARAGINASE moa
denies asparagine availability for protein synthesis
84
belomycin MOA
drug-ion complex oxidizes nucleotide deoxyribose
85
Anthracyclins
DNA intercolators, topo II inhibitors, free radical generators
86
Fludarabine MOA
bio activated in cell, produces DNA strand termination
87
interferon MOA
direct antiproliferative effect + immunomodulator
88
Imatinib moa
tki for BCR-ABL TK
89
methotrexate MOA
DHFRi
90
pentostatin moa
adenosine deaminase inhibitor that causes apoptosis
91
prednisone moa
inhibition of lymphocyte prolif
92
rituximab moa
CD20 mab that cuases adcc, cdc and direct apoptosis
93
vincristine
inhibitis mitotic spindle
94
arsenic toxicity
acute PML, differntiation syndrome + leukocytosis
95
asparaginase toxicity
bleeding, glucose intolerane
96
bleomycin toxicity
pulmonary fibrosis, alopecia pneumonitis
97
cyclophosphamide toxicity
BM supression, hemorrhagic cystitis
98
cytarabine toxicity
BM suppression and opp. infection
99
dacarbazine toxicity
BM supression hepatotoxicity, 2ndary malig
100
Vincristine toxicity
peripheral neuropathy paralytic illeus
101
pentostatin toxicitiy
renal failure, seizure, pulmonary edema
102
interferon toxicity
flue like symptoms ,myalgia, fever, neutropenia
103
Anthracylins toxicity
cardiotoxicity
104
only drug breast feeding might be ok
rituximab | *all other are no breast feeding
105
only drug proven to cause birth defects | *(category X)
methotrexate
106
Cat C drugs
asparaginase, dacarbazine, interferon, rituximab | *all others are Category D
107
drugs associated with paternal teratogenicity
``` cyslophosphamide doxorubicin epirubucin inf alfa 2a methotrexate ```

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