Leukemias

Question 1

What is the difference between acute and chronic leukemias?

Answer 1

• chronic –> slow growing
• acute –> fast growing

Question 2

What is chronic myeloid leukemia (CML)?

Answer 2

Unregulated myeloid proliferation from breaks in chromosome 9 & 22 which then form BCR-ABL fusion gene

Philadelphia Chromosome

Question 3

What are patients with chronic myeloid leukemia at risk for?

Answer 3

leukostasis

Question 4

What are the three stages of chronic myeloid leukemia?

Answer 4

• chronic phase
• accelerated phase
• blast crisis (terminal stage)

Question 5

What drug class is used in the treatment of chronic myeloid leukemia?

Answer 5

tyrosine kinase inhibitors

Question 6

What are the TKIs that can be used for CML?

Answer 6

• imatinib (1st)
• dasatinib (2nd)
• nilotinib (2nd)
• bosutinib (2nd)
• ponatinib (3rd)

Question 7

What side effect is associated with imatinib?

Answer 7

Nausea

Question 8

What side effect is associated with dasatinib?

Answer 8

Fluid retention (pleural effusion)

avoid acid reducers

Question 9

Which side effects are associated with nilotinib?

Answer 9

• QTc prolongation
• metabolic syndrome

Question 10

What side effect is associated with bosutinib?

Answer 10

diarrhea

Question 11

What side effects are associated with ponatinib?

Answer 11

• ischemic reaction
• vascular occlusion
• hypertension

Question 12

What is the benefit of ponatinib?

Answer 12

It is effective against mutations (even T315I)

Question 13

What are the TKI discontinuation/drug holiday criteria?

Answer 13

• No history of accelerated phase or blast phase
• Have to have been on TKI for at least 3 years
• Therapy needs to have resulted in BCR-ABL < 0.01% (deep molecular response)
• deep molecular response must be maintained for at least 2 years
• deep molecular response must be seen 4 times with test at least 3 months apart

Question 14

What are the risk factors for chronic lymphoid leukemia (CLL)?

Answer 14

• old
• white
• men

Question 15

How can CLL present?

Answer 15

recurrent sinus infection not resolved by antibiotics

Question 16

What is deletion 11q associated with in CLL?

Answer 16

• extensive lymphadenopathy
• disease progression
• shorter median survival

May respond well to fludarabine + alkylating agent

Question 17

What is deletion 17p associated with in CLL?

Answer 17

• the worst outcomes
• loss of TP53 gene
• poor response to chemo

Question 18

What is treatment reserved for in CLL?

Answer 18

• stage III or IV disease
• clinical symptoms
• end organ dysfunction

we do not treat based on lymphocyte count

Question 19

What are the first-line treatment options for CLL patients that do NOT have del17P nor TP53 mutation?

Answer 19

• BTK inhibitor +/- anti-CD20 mab (indefinite)

or

• venetoclax + obinutuzumab (one year)

BTK inhibitor: acalabrutinib or ibrutinib

Question 20

What are the first-line treatment options for CLL patients with del17p or TP53 mutation?

Answer 20

• BTK inhibitor +/- obinutuzumab (indefinite)

or

• venetoclax + obinutuzumab (one year)

BTK inhibitor: acalabrutinib or ibrutinib

Question 21

What are the main drug interactions for venetoclax?

Answer 21

• CYP3A4
• P-gp

Question 22

Which BTK inhibitor has the highest risk of atrial fibrillation?

Answer 22

ibrutinib

Question 23

What is a toxicity of all BTK inhibitors?

Answer 23

transient lymphocytosis

Question 24

How is acute myeloid leukemia (AML) diagnosed?

Answer 24

Bone marrow biopsy with greater than 20% blasts

Question 25

What are the two parts of acute myeloid leukemia (AML) treatment?

Answer 25

- Induction into remission - consolidation to prevent relapse

Question 26

What is the 7+3 treatment method for acute myeloid leukemia (AML)?

Answer 26

- daunorubicin (days 1-3) - cytarabine (days 1-7) | this is the induction

Question 27

What drug should be added to the induction regimen for a patient with AML who has FLT3 ITD?

Answer 27

midostaurin or quizartinib | FLT3 inhibitors

Question 28

What are the consolidation treatment options for AML?

Answer 28

- 3-4 cycles of high dose Cytarabine - venetoclax + hypomethylating agent (azacitidine) - allogenic stem cell transplant ##Footnote HiDAC is the option for favorable risk. Allogenic stem cell transplant is the choice for unfavorable risk AML.

Question 29

What are the side effects from high dose cytarabine? ##Footnote Used in AML consolidation

Answer 29

cerebellar side effects that mimic alcohol toxicity and could be irreversible

Question 30

When can venetoclax and azacitidine be used for induction in AML?

Answer 30

In patients older than 18 and ineligible for standard induction

Question 31

What are the low intensity chemotherapy options for AML? ##Footnote For patients not eligible for high dose cytarabine

Answer 31

- venetoclax + low dose cytarabine - azacitidine - low dose cytarabine - decitabine - clofarabine

Question 32

How is acute promyelocytic leukemia treated? ##Footnote subclass of AML

Answer 32

- all trans retinoic acid - arsenic trioxide

Question 33

What causes acute promyelocytic leukemia (APL)?

Answer 33

t(15:17) = PML:RARA

Question 34

What is acute lymphoblastic leukemia (ALL)?

Answer 34

Leukemic cells have growth advantage mutations and crowd out normal cells

Question 35

What are the treatment stages for ALL?

Answer 35

- induction - consolidation - maintenance

Question 36

What is the impact of Philadelphia chromosome positive on ALL?

Answer 36

worsens prognosis ##Footnote TKI will be added to multi-agent chemotherapy (dasatinib)

Question 37

What is the primary induction plan for ALL?

Answer 37

HyperCVAD

Question 38

What drugs are in HyperCVAD?

Answer 38

- hyper-fractionated cyclophosphamide - vincristine - doxorubicin (Adriamycin) - dexamethasone

Question 39

What are the consolidation options for ALL?

Answer 39

- multitarget therapy (cont HyperCVAD) or - allogeneic stem cell transplant

Question 40

What is a common regimen for ALL?

Answer 40

- Part A: HyperCVAD - Part B: methylprednisolone, methotrexate, cytarabine - Maintenance: 6-MP, methotrexate, prednisone, vincristine

Question 41

What is the indication for blinatumomab in ALL?

Answer 41

Approved for refractory or relapsed disease | Causes CRS and ICANS