L11 Acute Leukemia

Question 1

Comment on the differences in site and spread between leukemia and lymphoma.

Answer 1

1. Site
   Leukemia: arises from bone marrow
   Lymphoma: arises in lymph nodes and extranodal tissues
2. Spread
   - Both can spread to elsewhere like blood
   - leukemia: can spread to LN
   - lymphoma: can spread to BM

Question 2

> 20% of blast cells in PB/BM, characterized by continuous proliferation but failure of differentiation
?

Answer 2

Acute leukemia

Question 3

Typical age of presentation
A. ALL: children and young adults
B: CLL: 40-60 years old
C. AML, CLL: 60+ years old

Answer 3

All except A:

should be old adults

Question 4

What are the genetic predisposition risk factors for leukemia?

Answer 4

1. Down’s syndrome
2. Fanconi’s anemia
3. Bloom syndrome

Question 5

Other than genetic predeposition, what are the other risk factors for leukemia?

Answer 5

1. Previous exposure to chemotherapy, radiation and chemicals (benzene)
2. PMH of MDS or MPN

Question 6

Suggest the bloom film presentation in acute leukemia patients. (3 typeds of blood cells) > symptoms?

Answer 6

Pancytopenia due to bone marrow failure

• anemia: pallor, fatigue
• thrombocytopenia: bleeding tendency, intracranial hemorrhage, DIC
• neutropenia: infection, fever

***Leukocytosis: hyperviscosity due to increased circulating blasts (to stop other white cells from proliferating, like neutrophil) : visual disturbance, headache, vertigo

Question 7

Blood viscosity _________ in acute leukemia, why?

Answer 7

increases (hyperviscosity syndrome)

- due to increase in WBC (hyperleukocytosis)

Question 8

In acute leukemia, there might be possible organ infiltraion.

List 4 examples for ALL.

Answer 8

1. Bone pain
2. Lymphadenopathy
3. Testicular swelling
4. CNS symptoms (meningeal involvement)

Question 9

What is the possible organ infiltration in T-ALL (T cell Acute lymphoblastic leukemia)?

Answer 9

SVCO (SVC obstruction) - mediastinal mass

Question 10

Which kind of acute leukemia will show clinical symptom of organ filtration in the gum (Gum hypertrophy)?

Answer 10

AML M5

acute monocytic/ monoblastic leukemia

Question 11

What are the types of acute leukemia under the myeloid lineage?
(6)

Answer 11

1. AML related to recurrent genetic abnormalities
2. Myeloid proliferations related to Down’s syndrome
3. AML with mylodysplastic-related changes
4. Therapy-related myeloid neoplasm
5. Myeloid sarcoma (extramedullary tumor with myeloblasts)
6. AML, NOS (not otherwise specified)

Question 12

What are the types of acute leukemia under the lymphoid lineage? (3)

Answer 12

1. Precursor B cell
2. Precursor T cell
3. ALL of ambiguous lineage (acute undifferentiated leukemia)

Question 13

In B-ALL with hyperdiploidy (>50chromosomes) has _____ pronosis.

Answer 13

better

Hypodiploidy: poor prognosis

Question 14

What are the characteristic features of AML-M3 Acute promyelocytic leukemia (APL)?

Answer 14

• with Auer rods

- DIC

Question 15

What are the characteristic features of AML-M5 Acute monocytic leukemia?

Answer 15

• without Auer rods

- with gum hypertrophy

Question 16

Difference in size of morphology of blast in AML and ALL?

Answer 16

AML: big and numerous
ALL: small and few

Question 17

Which of the following about myeloblast are true?
A. they are big and numerous compared to lymphoblasts
B. they have fine granules
C. they have fine chromatin
D. they have prominent nucleoli
E. absent auer rods
F. Faggot cells are present in APL (promyelocytic leukemia)

Answer 17

All except E
Auer rods +

APL: Faggot cells (= promyelocytes with Auer rods ++)

Question 18

Which of the following about lymphoblasts are true?
A. they have very high N:C ratio
B. they have fine chromatin
C. they have agranular cytoplasm
D. absent auer rods 
E. indistinct nucleoli

Answer 18

All except B

clumped chromatin

Question 19

Give 4 examples of myeloid markers.

Answer 19

1. CD33
2. CD13
3. CD17
4. MPO (myeloperoxidase)

Question 20

Give 5 examples of B-lymphoid markers (present in 80% of B-ALL)

Answer 20

1. CD10
2. CD19
3. CD20
4. CD22
5. CD79a

Question 21

Give 4 examples of T-lymphoid markers (present in 15% of T-ALL)

Answer 21

1. CD2
2. cCD3 (cytoplasmic CD3)
3. CD5
4. CD7

(pneumonic: prime numbers, prime= killing=T cells)

Question 22

What method is used for diagnosing, finding pathophysiology, treatment and prognosis, even for detecting MRD? (minimal residual disease)

Answer 22

Genetics studies

e.g. G-banding, FISH, molecular genetic study: RT-PCR, NGS

Question 23

What does PML-RARA indicate in G-banding?

Answer 23

APL
acute promyelocytic leukemia

(FISH can detect it also)

Question 24

Translocation of chromosomes 9 and 22 + Ph+ =?

Answer 24

B-ALL with poor pronosis

Question 25

List 3 possible mutations which can be detected by PCR in AML patients. (also list the prognosis)

Answer 25

1. FLT3-ITD mutation: poorer prognosis, FLT3 inhibitors under trial 2. NPM1 mutation: better prognosis 3. CEBPA biallelic/ double mutation: better prognosis

Question 26

List the possible complications to be screened in acute leukemia patients.

Answer 26

1. DIC in APL 2. Extra-medullary involvement (myeloid sarcoma: biopsy/ lumbar puncture: ALL) 3. Tumor-lysis syndrome (TLS) 4. Septicemia: blood culture

Question 27

General treatment for APL/ALL patients?

Answer 27

1. Chemotheraphy - APL: ATRA (all-trans retinoic acid), arsenic trioxide 2. Gene-targeted therapy - tyrosine kinase injibitor for BCR-ABL-1 + ALL 3. Chemotherapy + Allogenic stem cell transplantation - poor prognosis cases

Question 28

How is acute promyelocytic leukemia treated? (APL) | =AML-M3

Answer 28

1. before definite genetic diagnosis is reached (PML-RAR): - ATRA (tretinoin) based on clinical and morphological (faggot cells) crieteria 2. PML-RARA: - ATRA to promote differentiation - Arsenic trioxide to promote apoptosis

Question 29

How is APL monitored?

Answer 29

RQPCR of PML-RARA (minimal residue disease MRD)

Question 30

Difference between acute and chronic leukemia?

Answer 30

Acute leukemia: accumulation and proliferation of precursor cells or undifferentiated cells Chronic leukemia: accumulation and proliferation of mature and differentiated cells

Question 31

Plasma cell myeloma is resulted from clonal proliferation of?

Answer 31

Plasma cells

Question 32

What are the other possible diseases that mimic acute leukemia clinically?

Answer 32

1. Aplastic anemia | 2. Marrow infiltration by other malignancies