CML/CLL Flashcards

1
Q

Average age of diagnosis in CML

A

64

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2
Q

Average age of diagnosis of CLL

A

70

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3
Q

T/F there are more NEW cases of CML than CLL

A

False

CLL > CML

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4
Q

T/F there are more deaths from CML than CLL

A

False

CLL > CML

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5
Q

What is the most common leukemia in the US?

A

CLL

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6
Q

T/F CLL is idiopathic?

A

True

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7
Q

T/F you usually know the cause of CML

A

False

Usually do not know

  • likely increased by environmental exposure which damage chromosomes
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8
Q

Pathophysiology of CML

A
  • reciprocal translocation b/t chromo 9 & 22
  • shorted arm of chromo 22 = Ph chromo
  • creates fusion gene bcr-abl
  • creates TK
  • constitutively active
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9
Q

What blast % is found in chronic phase of CML?

A

<10% in peripheral blood or bone marrow

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10
Q

What blast % is found in accelerated phase of CML?

A

10-29% in peripheral blood and bone marrow

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11
Q

What blast % is found in blast crisis in CML?

A

>30% in peripheral blood and bone marrow

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12
Q

How long does chronic phase of CML last?

What is it associated with?

A

can last for years

Associated with funcitonal myeloblasts

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13
Q

How long does the accelerated phase of CML last?

What is it associated with?

A

Lasts weeks

Associated with therapy resistance and disease progression

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14
Q

How long can you live in blast crisis in CML?

A

Die in days to weeks

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15
Q

Without treatment, CML disease progresses within how many years?

A

~5 years

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16
Q

What can be used to quickly lower WBC in CML?

A

Hydroxyurea

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17
Q

What can be used if WBCs are dangerously high in CML?

A

leukophoresis

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18
Q

What drug can decrease WBC the slwoest in CML?

A

TKIs

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19
Q

T/F hydroxyurea can help slow disease progression in CML

A

False

TKIs help slow disease progression

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20
Q

Which TKI is the ONLY one that works for T3151 mutation in CML?

A

Ponatinib

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21
Q

Imatinib binds the inactive/active confimation of bcr-abl?

A

inactive

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22
Q

Nilotinib binds the inactive/active confimation of bcr-abl?

A

inactive

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23
Q

Dasatinib binds the inactive/active confimation of bcr-abl?

A

active

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24
Q

Bosutinib binds the inactive/active confimation of bcr-abl?

A

both!

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25
Q

What is a complete hematologic response (CHR)?

A

normalization of peripheral blood counts

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26
Q

What is a major cytogenetic response (MCR)?

A

= 35% Ph+ cells on metaphase in bone marrow

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27
Q

What is major molecular remission (MMR)?

A

PCR shows 3 log decline in bcr-abl from baseline

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28
Q

What is complete molecular remission (CMR)?

A

PCR shows 4-5 log decline in BCR-abl from baseline

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29
Q

MMR =

A

109 cells

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30
Q

T/F IFN-a is used in CML

A

False

used to be, but not anymore!

  • dose related and required life-long tx
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31
Q

Imatinib is 1st gen/2nd gen

Dasatinib is 1st gen/2nd gen

A

Ima: 1st

Das: 2nd

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32
Q

What is IFNa usually combined with for CML treatment?

A

ARA-C

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33
Q

T/F IFNa + ARA C is better than imatinib in CML

A

False!

Ima > IFNa + ARA C

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34
Q

Toxicities of Imatinib

A
  • hepatoxic
  • hematologic tox

- fluid retention

  • muscle pain/cramps

GI symptoms

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35
Q

What to tell patient on imatinib

A

Take with food and large glass of water

DDI with warfarin: increase INR; consider therapy modification

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36
Q

T/F imatinib is more potent than dasatinib

A

false

das 300x > ima

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37
Q

T/F dasatinib has no difference in overall or progression free survival compared to imatinib

A

true

  • increased response rates though
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38
Q

Dasatinib has an increased rates of what toxicities compared to imatinib

A

pleural effusions

QT prolongation

39
Q

Toxicities of dasatinib

A

pleural effusions

QT prolongation

PAH: potentially fatal!

40
Q

Imatinib DDIs

A

3A4, 2Ds and pgp inhibitor

41
Q

Dasatinib DDIs

A

pH dependent: decreased abs with PPI and H2 antag

3A4, PGP inhibitor

42
Q

Which has a deeper response: imatinib or dasatinib?

A

Dasatinib!

4-5 log decline (CMR)

43
Q

T/F nilotinib has a higher rate of response to imatinib

A

true!

but no difference in overall or progression free survival!

44
Q

T/F imatinib has higher rates of cardiovascualr events than nilotinib

A

false!

Nilo > ima

45
Q

Boxed warning for nilotinib

A

QT prolongation

46
Q

Nilotinib has lower rates of what ADE compared to imatinib

A

fluid retention

GI symptoms

47
Q

Unique ADE of nilotinib

A

may cause metabolic effects

48
Q

T/F Nilotinib has an equal molecular response compared to imatinib

A

false

greater response!

4 log decline (MMR)

49
Q

4 log decline

A

MMR

50
Q

4-5 log decline

A

CMR

51
Q

T/F dose doesn’t affect toxicities with nilotinib

A

false!

dose related toxicity

52
Q

Unique ADE of bosutinib

A

Diaraha and skin toxicity

53
Q

T/F bosutinib is more likely to cause QT prolongation compared to nilotinib

A

false!

Nil > bos

54
Q

Which TKI in CML is multi-targeted?

A

ponatinib

55
Q

Toxicities of bosutinib

A

thromboembolism

liver tox

HF

vascular tox

56
Q

T/F it is not a good idea to get patients off of TKIs in CML

A

False!

good idea!

57
Q

When can you think about stopping TKIs in CML?

A
  • after DEEP molecular response >/= 2 years
  • patient consent
  • discussed risk/benefits
  • have chronic phase
  • no previous history of accelerated or blast phase
  • on TKI for 3 years
58
Q

When would you restart TKI therapy in CML?

A

after recurrence (~6 months)

59
Q

T/F almost all patients will re-establish molecular response when TKI restarted in CML

A

true

60
Q

What is a risk of discontinuing TKIs?

A

TKI withdrawal

61
Q

How long must you be on TKI therapy in CML before discontinuing?

A

at least 3 years

62
Q

How long should you have a stable molecular response in CML before discontinuing TKIs?

How many tests?

How long apart are the tests?

A

2 years

4 tests

3 months apart

63
Q

How often do you monitor after discontinuing TKIs?

A
  • monthly x 1 year
  • Q6 weeks thereafter
64
Q

Prompt resumption of TKI within ____ weeks of loss of MMR

A

4

65
Q

What to tell patient on dosatinib

A

take with or without meals

Avoid H2 antagonists/PPIS

66
Q

What to tell patient on niloinib

A

avoid food 2 hours before or 1 hour after dose

avoid drugs that prolong QTc

67
Q

What to tell patient on bosutinib

A

take with food

avoid PPIs (decrease abs)

68
Q

What to tell patient on ponatinib

A

take with or without food

69
Q

Which TKI in CML can also be used in ALL?

A

ponatinib

70
Q

Which TKI should you avoid in CML with lung disease?

A

dasatinib

71
Q

What non-TKI drug has activity against T3151 mutation in CML?

What is the MOA?

A

omacetaxine

protein synthesis inhibitor

72
Q

Major toxicity of omacetaxine

A

bone marrow suppression

73
Q

When would you use omacetaxine?

A

Intoelrant or unresponse to 2 prior TKI therapies in CML and ponatinib

74
Q

What is the only proven curative therapy in CML?

A

allogenic stem cell transplant

75
Q

Pathophysiology of CLL

A

Neoplastic clone of CD5+ B lymphocytes

loss of normal apoptosis

76
Q

What mutations are common in CLL and can be used as biomarkers?

A

TP53

del(17p)

77
Q

S/S of CLL

A

fatigue

fever (w/o infection)

night sweats

weight loss

78
Q

Physical exam of CLL

A

lymphadenopathy

splenomegaly

hepatomegaly

79
Q

Peripheral blood labs in CLL

A

lymphocytosis

autoimmune hemolytic anemia

hyepr/hypoagammaglobulinemia

thrombocytopenia

80
Q

Bone marrow labs in CLL

A

hypercellular

increase mature lymphocytes

increased megakaryocytes

81
Q

Tx: CLL w/o del/mutation

< 65 yo w/o signif co-morbidities

A

FCR regimen

bendamustine + CD20 mab

Ibruitnib

82
Q

Tx: CLL w/o del/mutation

> 65 yo or younger patients with co-morbidities or frail patients

A

Obinutuzumab + chlorambucil

Ibrutinib

Bendamustine + CD20 mab

Rituximab + chlorambucil

Ofatumumab + chlorambucil

83
Q

Tx: CLL w/o del/mutation

Post 1st line maintence therapy

A

lenalidomide

84
Q

Tx: CLL w/o del/mutation

Relapsed/refractory

A

ibrutinib

venetoclax + rituximab

Duvelisib

Idelalisib + rituximab

85
Q

Tx: CLL WITH del/mutation

A

Ibrutinib

post 1st line: lenalidomide

86
Q

What to tell patient on lenalidomide

A

Risk of DVT/PE: prophylaxis with ASA 81 mg

teratogen: contraception for males and females

87
Q

Main ADE of ibrutinib

A

severe diarrhea –> hydration, loperamide

myelosuppression

88
Q

When is venetoclax used in CLL?

A

relasped or refractory CLL

89
Q

Major ADE of venetoclax (according to McGuire)

A

TLS

severe diarrhea

myelosuppression

90
Q

Which drugs in CLL can have infusion related reactions and need premed?

A

Rituximab: APAP, benadryl

Ofatumumab: same + steroid

Obinutuzumab: same + steroid

91
Q

Is infection more common in CLL or CML?

A

CLL

92
Q

What vaccines to give CLL patients

A

No live!

annual flu

pneumococcal Q5 years

93
Q

What antibiotics to give to prevent infection in CLL patients

A

Herpes: acyclovir

PJP: SMP/TMX

HBV: entecavir if HBsAg+

94
Q

What is a complete cytogenetic remission (CCyR)?

A

0% Ph+ cells on metaphse in the bone marrow