Leukemias1

Question 1

Two types of Leukemias

Answer 1

Acute myeloid leukemia (AML)
and
Acute lymphoblastic leukemia (ALL)

Question 2

ALL demographics

Answer 2

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

Question 3

Two types of ALL

Answer 3

B-lymphoblastic ALL (B-ALL)

T-ALL

Question 4

3 types of B-ALL

Answer 4

B-ALL with:

1. BCR-ABL1
2. MLL
3. ETV6-RUNX1

Question 5

3 types of AML

Answer 5

Q

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

Question 6

5 cytogenic abnormalities for congenital AML

Answer 6

AML with:

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

Question 7

2 causes of therapeutic AML

Answer 7

1. aklylating agent + radiation

2. topoisomerase II inhibitors

Question 8

molecular findings leading to AML-NOS

Answer 8

1. FLT3 ITD
2. NPM1
3. CEPBA

Question 9

“leukemic stem cell” theory

Answer 9

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

Question 10

risk factors for acute leukemia

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

Answer 10

• 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)

Question 11

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

Answer 11

• 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

Question 12

Rare signs and symptoms of acute leukemia

Answer 12

• 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

Question 13

ALL and AML generic marker of immaturity

Answer 13

CD34

Question 14

ALL lymphoblast marker (not mature lymphocyte)

Answer 14

Tdt

Question 15

ALL markers of B cell lineage

Answer 15

CD19,

CD22

Question 16

ALL markers of T cell lineage

Answer 16

CD3, CD7

Question 17

B-ALL

• patient age
• sex
• manner of manifestation
• prognosis.

Answer 17

○ Age: more frequent in neonates and young children
○ Sex: Females > Males
○ Manifestation: B-cell lineage antigens, lack markers of mature B-cells
○ Prognosis: complete remission >95%; cure around 80%

Question 18

Does B-ALL express CD20?

Answer 18

No.

-express CD19, CD22

Question 19

T-ALL

• patient age
• sex
• manner of manifestation
• prognosis.

Answer 19

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

Question 20

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

Answer 20

B-ALL: 75% of all ALL cases

T-ALL: 25% of all ALL cases

Question 21

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

-prognosis?

Answer 21

25% cases of adult B-ALL, 2% of childhood B-ALL
(more common in adults)
- Ph+: worst prognosis of any ALL!

Question 22

Pt age group of (B-ALL) MLL

-prognosis?

Answer 22

a. Most common in neonates and young infants
b. Poor prognosis
* MLL of both B-ALL and congenital AML MLL have poor prognosis

Question 23

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

-prognosis?

Answer 23

a. 25% of cases of childhood B-ALL

b. Very favorable prognosis!

Question 24

5 factors affecting prognosis in ALL

Answer 24

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

Question 25

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

Answer 25

B-ALL

Question 26

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

Answer 26

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

Question 27

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

Answer 27

1. Increased myeloblasts accounting for 20% or more of nucleated cells in the marrow or peripheral blood 2. cytogenetic findings - CD34 - CD117 (C-Kit) Myeloperoxidase

Question 28

clinical significance of Auer rod

Answer 28

clinical significance of Auer rod Q 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.

Question 29

``` 5 cytogenic abnormalities for congenital AML: Prognosis and Pt population 1. RUNX1-RUNX1T1 2. CBFB-MYH11 3. RBM15-MKL1 4. PML-RARA (APL) 5. MLL Q reveal answer ```

Answer 29

1. RUNX1-RUNX1T1: - younger patients - good prognosis 2. CBFB-MYH11: - younger patients - good prognosis 3. RBM15-MKL1 - infants with down syndrome - good prognosis

Question 30

5 cytogenic abnormalities for congenital AML: 4. PML-RARA - % of AML 5. MLL - prognosis?

Answer 30

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

Question 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)

Answer 31

1. Don't need chemo! - treat with all trans retinoic acid (ATRA) 2. APL is associated with DIC

Question 32

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

Answer 32

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

Question 33

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

Answer 33

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

Question 34

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

Answer 34

Poor