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Flashcards in Acute Leukemia (Goorha) Deck (59):
1

What are the two divisions of acute leukemia?

acute myeloid and acute lymphoblastic leukemia

2

What cellular feature is characteristic of leukemia?

accumulation of malignant WBCs in BM and blood

3

What causes the morbidity and mortality associated with leukemia?

1. BM failure
(anemia, neutropenia, thrombocytopenia)

2. Infiltration of organs
(such as liver, spleen, lymph nodes, meninges, brain, skin, testes)

4

FAB classification of acute myeloid leukemia:

M0-M7

5

FAB classification of acute lymphoblastic leukemia:

L1-L3

6

Most common form of leukemia in children

ALL

7

Acute leukemia that occurs in all age groups:

AML

8

Highest in kids ages 3-7

ALL

9

Increasingly common with advanced age

AML

10

What is the difference between primary and secondary AML?

primary AML = de novo

secondary AML develops from myelodysplastic syndrome or other hematatological malignancies

11

Which is more difficult to treat: primary or secondary AML?

secondary

12

Acute leukemia that shows a notable rise in patients around 40 years old:

ALL

13

Three treatment phases of ALL:

1. remission induction
2. consolidation (intensification)
3. maintenance

14

Why is allopurinol administered to ALL patients receiving treatment?

it counters hyperuricemia resulting from tumor cell breakdown

15

Do adults or children with ALL have better cure rate? Why?

Children; this is possibly due to worse genetic features in adults

16

Disorders associated with causing acute leukemia (etiology):

1. Myelodysplastic syndromes
2. Myeloproliferative diseases
3. Down’s syndrome
4. Fragile chromosome syndromes (Fanconi’s anemia)
5. Aplastic anemia + Paroxysmal Nocturnal Hemoglobinuria

17

Etiologies of acute leukemia related to exposure:

1. Idiopathic (vast majority)
2. Prior chemotherapy
3. Prior radiotherapy
4. Chemical exposure (benzene)

18

Where does malignant transformation occur in acute leukemia?

hematopoetic stem cells or early progenitors

19

What does genetic damage lead to, in acute leukemia?

(1) increased rate of proliferation
(2) reduced apoptosis
(3) block in cellular differentiation

20

Collectively, what is the result of genetic damage associated with acute leukemia?

accumulation of blast cells (early BM hematopoietic cells)

21

Acute leukemia is defined as:

1. > 20% blasts in blood or BM
2. cytogenetic or molecular genetic abnormalities (even if blasts are <20%)

22

T/F: Acute leukemias are aggressive diseases.

T: no treatment = death

23

What is immunotyping (in terms of AML/ALL)?

analysis of the pattern of antigen expression on surface of blast cells

24

What is FAB AML classification M0?

undifferentiated

25

What are FAB AML classification M1 and M2?

M1: no maturation
M2: granulocytic maturation

26

What is FAB AML classification M3?

acute promyelocytic

27

What is FAB AML classification M4?

granulocytic and monocytic maturation

28

What is FAB AML classification M5?

monoblastic or monocytic

29

What are FAB AML classification M6 and M7?

M6: erythroleukemia
M7: megakaryocytic

30

What is FAB ALL classification L1?

small, uniform blast cells with a high nucleus:cyto ratio

31

What is FAB ALL classification L2?

larger, heterogenous blast cells with a lower nucleus:cyto ratio

32

What is FAB ALL classification L3?

blasts with vacuoles and basophilic cytoplasm

33

What morphologic structure is diagnostic of AML?

auer rods

34

What tests may be useful when trying to differentiate between ALL and AML?

chromosomal/genetic analysis
Immunological markers (flow cytometry)

35

4 myeloid antigens:

MPO
CD33
CD13
HLA-DR

36

4 lymphoid antigens:

TdT
CD10
CD19
CD20

37

What is an example of a genetic translocation linked to acute promyelocytic leukemia?

t(15;17)

38

How do ATRA and arsenic counter an oncoprotein (or fusion oncoprotein)?

--Oncoprotein (gene product) binds to DNA and activates self-renewal of leukemic stem cells
--ATRA/arsenic releases the co-repressors bound to the DNA ("deprogramming" leukemia self-renewal)
--Normal transcription can now occur, allowing cell to differentiate into a normal cell

39

What's the diagnosis?
elevated WBC and smear showing auer rods

AML

40

How does determining the specific genetic defect associated with an acute leukemia improve patient's outcome?

useful in determining pronosis/treatment

41

What is remission induction therapy (AML)?

1 to 2 courses of intensive therapy to achieve a complete response (no detectable leukemia cells)

42

What is post-remission therapy (AML)?

"consolidation therapy", in which 3 to 4 courses of intensive short-course therapy are used to further reduce the subclinical effects of a tumor

43

What often follows post-remission therapy (AML)?

Either:
1. maintenance therapy: months to years of less intensive therapy (further prevents recurrence )
2. allogeneic bone marrow transplantation

44

T/F: AML treatment is more favorable for older patients.

F: younger patients (perhaps because they tolerate chemo better)

45

What are 4 treatment strategies for older adults with AML?

1. Supportive care
2. Standard intensive chemotherapy, not clear that any consolidation is beneficial
3. New agents (noncytotoxic agents)
4. Reduced-intensity conditioning HSCT (has shown a more favorable response than traditional high-intensity treatment)

46

What genetic abnormalities are associated with poor outcomes in adults and children will ALL?

MLL-AF4 and BCR-ABL translocations

47

What genetic abnormalities in childhood ALL (rare in adults) are associated with a good outcome?

E2A-PBX and TEL-AML
("abnormalities of hyperdiploidy")

48

What is the prophylactic CNS treatment in ALL?

intrathecal methotrexate or ARA-C

49

What are maintenance therapy drugs used in ALL?

6-MP, methotrexate, prednisone

50

What are induction therapy drug options for ALL?

1. VCR
2. L-ASP
3. DEX
4. PRED +/- Daunorubicin

51

What are consolidation therapy drug options for ALL?

1. Daunorubicin
2. HD Ara-C
3. VCR
4. Etoposide
5. thioguanine or 6-mercaptopurine
6. cyclophosphamide
7. L-ASP

**do we need to know this??

52

In acute leukemia, therapy is tailored to:

specific genetic abnormalities

53

What are 4 ways to improve outcomes, in terms of treatment?

Treatment at specialized centres
Clinical Trials
Immunotherapy
Stem Cell Transplantation

54

Molecular abnormality associated with poor prognosis in AML:

FLT3-ITD

55

Molecular abnormality associated with intermediate prognosis in AML (in addition to cytogenetic abnormalities):

c-KIT

56

3 cytogenetic abnormalities associated with good risk in AML:

1. inv(16)
2. t(8;21)
3. t(15;17) **ATRA

57

What would you use to treat APML (M3), according to the lecture?

ATRA/ARA-C
Anthracycline

58

What would you use to treat inv(16) or t(8;21), according to the lecture (in addition to standard induction)?

high dose ARA-C
ultimately, allograft

59

How would you treat a patient positive for FLT3-ITD versus one that was negative?

positive: allograft ASAP
negative: high dose ARA-C, allograft if needed