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Flashcards in 2 BL Acute leukemias Deck (34):
1

Two types of Leukemias

Acute myeloid leukemia (AML)

and

Acute lymphoblastic leukemia (ALL)

2

ALL demographics

75% of cases of ALL occur in children under 6 years old

3

Two types of ALL

B-lymphoblastic ALL (B-ALL)

T-ALL

4

3 types of B-ALL

B-ALL with:
1. BCR-ABL1
2. MLL
3. ETV6-RUNX1

5

3 types of AML

1. Congenital
2. Therapeutic
3. AML, NOS (not otherwise specified)

6

5 cytogenic abnormalities for congenital AML

AML with:
1. RUNX1-RUNX1T1
2. CBFB-MYH11
3. PML-RARA (APL)
4. RBM15-MKL1
5. MLL

7

2 causes of therapeutic AML

1. aklylating agent + radiation
2. topoisomerase II inhibitors

8

molecular findings leading to AML-NOS

1. FLT3 ITD

2. NPM1
3. CEPBA

9

"leukemic stem cell" theory

• Theory suggests that chemo only kills differentiating or differentiated cells, so you don't kill the LSCs. As a result, the cancer can recur.

10

risk factors for acute leukemia

(dont forget: majority of acute leukemias occur in the apparent absence of risk factors)

• Previous chemotherapy, especially DNA alkylating agents and topoisomerase-II inhibitors
• Previous exposure of active marrow to ionizing radiation
• Tobacco smoke
• Benzene exposure
• Genetic syndromes (Down Syndrome, Bloom, Fanconi, ataxia-telangiectasia)

11

signs and symptoms of acute leukemia at initial presentation. What are they due to?

• Signs and symptoms are because normal cells in the marrow are replaced by leukemic cells
○ anemia: fatigue, malaise, pallor, dyspnea
○ thrombocytopenia: bruising, petechiae, hemorrhage
○neutropenia: fever, infections

12

Rare signs and symptoms of acute leukemia

• Thrombocytic events are due to increased blood viscosity (known as leukostasis and is seen where WBC count is very high)

• DIC can be initiated by some leukemic cells

• Direct infiltration of skin, gums, lymph nodes, and other tissues

13

ALL and AML generic marker of immaturity

CD34

14

ALL lymphoblast marker

TdT

- common lymphoblast marker (not on mature lymphocyte)

15

ALL markers of B cell lineage

CD19,
CD22

16

ALL markers of T cell lineage

CD3
CD7

17

B-ALL
- patient age
- sex
- manner of manifestation
- prognosis.

○ Age: more frequent in neonates and young children
○ Sex: Females > Males
○ Manifestation: B-cell lineage antigens, lack CD20 markers of mature B-cells
○ Prognosis: depends

18

Does B-ALL express CD20?

No.

Not on mature B cells

-express CD19, CD22, CD34

19

T-ALL
- patient age
- sex
- manner of manifestation
- prognosis.

○ Age: more frequent in adolescents and young adults
○ Sex: Males > Females
○ Manifestation: T-lymphoblastic lymphoma, (mediastinal mass). Elevated WBC.
○ Prognosis:
- adults: complete remission 60-80%; 50% cure
-children: cure rates >95% remission , 80% cure

20

% of ALL cases. How much B-ALL, how much T-ALL?

B-ALL: 75% of all ALL cases
T-ALL: 25% of all ALL cases

21

Pt age group of (B-ALL) BCR-ABL1
-prognosis?

25% cases of adult B-ALL, 2% of childhood B-ALL
(more common in adults)

- Ph+: worst prognosis of any ALL!

22

Pt age group of (B-ALL) MLL
-prognosis?

a. Most common in neonates and young infants
b. Poor prognosis

*MLL of both B-ALL and congenital AML MLL have poor prognosis

23

Pt age group of (B-ALL) ETV6-RUNX1
-prognosis?

a. 25% of cases of childhood B-ALL
b. Very favorable prognosis!

24

5 factors affecting prognosis in ALL

1. Age
2. White blood cell count
3. Slow response to therapy / small amounts of residual disease after therapy
4. Number of chromosomes
5. B versus T lineage

25

What has worst prognosis, B-ALL or T-ALL?-ALL

B-ALL

26

What is the prognosis for ALL with regards to hyperdiploidy vs hypodiploidy?

very favorable prognosis for hyperdiploidy (>50 but <46 chromosomes).

27

2 types of findings that would allow for a diagnosis of AML.

1. Increased myeloblasts accounting for 20% or more of nucleated cells in the marrow or peripheral blood

2. cytogenetic findings
- CD34 (on myeloblasts)
- CD117 (C-Kit)
- Myeloperoxidase marker

28

clinical significance of Auer rod

Myeloblasts are very generic looking, can be confused with lymphoblasts unless you see Auer rods!

• Not only does the presence of an Auer rod tell you that you have a myeloblast, it means you have an ABNORMAL myeloblast.

29

Here are 3/5 cytogenic abnormalities for congenital AML: Prognosis and Pt population?
1. RUNX1-RUNX1T1
2. CBFB-MYH11
3. RBM15-MKL1

1. RUNX1-RUNX1T1:
- younger patients
- good prognosis

2. CBFB-MYH11:
- younger patients
- good prognosis

3. RBM15-MKL1
- infants with down syndrome
- good prognosis

30

Here are 2/5 cytogenic abnormalities for congenital AML:

4. PML-RARA
- % of AML?
5. MLL
- prognosis?

4. PML-RARA (APL)
- 5-10% of all AML
- prognosis not stated

5. MLL
- Poor prognosis
- Pt not stated

31

two reasons why it is important to recognize at initial diagnosis that a case of AML is the AML with t(15;17)(aka acute promyelocytic leukemia (APL)

1. Don't need chemo!
- treat with all trans retinoic acid (ATRA)

2. APL is associated with DIC

32

2 main categories of therapy-related AML, and compare their latency and prognosis.

1. t-AML secondary to alkylating agents or radiation:
- Latency of 2-8 years from prior treatment
- POOR prognosis

2. t-AML secondary to topo-II inhibitors:
- Latency period of 1-2 years from prior treatment
- POOR prognosis

33

3 molecular markers (abnormalities) currently used to predict prognosis in patients with AML with normal karyotype

1. FLT3 - Internal tandem duplication
2. Nucleophosmin-1 : NPM1 mut.
3. CEBPA mutation

34

Which of the 3 molecular markers for AML NOS has poor prognosis (driving prognostic factor)?

FLT3