Sweatman Hematologic Malignancies Flashcards Preview

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Flashcards in Sweatman Hematologic Malignancies Deck (107):
1

What are we trying to achieve with Heme. Malignancy drugs

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

2

Consequence of myelosupression

opportunistic infection risk goes up considerable

3

Induction

high dose: intolerable chronically

4

Consolidation

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

5

Maintainence

long term tolerable, lower dose therapy during remission

6

Adjuvant

after sx/ radiotherapy

7

neo-adjuvant

before sx/ radiotherapy

8

Metronomic dosing used for

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

9

Metronimic therapy work by

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

10

how can metronomic dosing affect a tumor

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

11

explains phenotypic divergence arising from applied chemo and the coinciding resistance

adaptive therapy

12

explain adaptive chemotherapy treatment

control vs eradication

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

13

most common toxc effects of metronomic dosing

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

14

more than half the leukemias present

acutely

15

Most common in children 3-7

ALL

16

Most commonly seen in elderly

CLL

17

Ph1 chromosome most commonly seen in (3)

CML (210)> ALL(190)>AML
*detectable by FISH or PCR

18

AML tx regimine
*INDUCTION*

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

19

MOA for Daunorubicin

free radical producer
intercolater
topo II inhibitor

20

Cytarabine MOA

pyrimidine antimetabolite

21

Thioguanine MOA

purine antimetabolite

22

Daunorubicin class

anthracycline

23

Side effect of Daunorubicin

cardiac toxicity and arrhythmia

24

Side effects of AML induction regimine

all are myelosupressors--> opportunistic infection

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