ALL

Question 1

What is the main characteristic feature of ALL?

Answer 1

development of a large number of immature lymphocytes/lymphoblasts

Question 2

What are the S+S of ALL?

Answer 2

1. Bruising or bleeding
2. Pallor + fatigue
3. Infection (recurrent)
4. Bone/joint pain
5. Enlarged lymph nodes, liver and/or spleen

(there are way more, but this is probably enough)

Question 3

Explain why the following symptoms arise:

1. Bruising or bleeding
2. Pallor + fatigue
3. Infection (recurrent)
4. Bone/joint pain

Answer 3

1. Bruising or bleeding due to thrombocytopenia
2. Pallor + fatigue due to anaemia
3. Infection (recurrent) due to neutropenia
4. Bone/joint pain (increased cell production = bone marrow expansion)

Question 4

Which chromosome abnormality is commonly implicated in Pro-B ALL?

Answer 4

MLL translocation (also known as KMT2A according to Wiki)

but the lecture said MLL, so stick to that x

Question 5

Which chromosome abnormality is commonly implicated in Pre-B ALL?

Answer 5

High hyperdiploidy or ETV6-RUNX1 translocation

Question 6

Give examples of common and rare mutations associated with ALL?

Answer 6

Common:

• ARID5B
• CDKN2A/2B
• CEBPE
• IKZF1
• GATA3
• PIP4K2A

Rare:
- TP53

Question 7

Why is Down’s syndrome a risk factor for ALL?

Answer 7

• a common translocation in ALL is on chromosome 12 and 21
• in Down’s syndrome there is trisomy 21
• more chromosome 21 increases likelihood of translocation occurring

Question 8

Apart from genetic abnormalities, what are the other risk factors of ALL?

Answer 8

• environmental:
  1. high levels of radiation exposure
  2. high birth weight
  3. secondary leukaemia (after treatment with certain chemotherapies)

also delayed infection hypothesis

Question 9

What test gives conclusive proof for a diagnosis of ALL? How does it do this?

Answer 9

Bone marrow biopsy

>20% fo all cells being leukaemic lymphoblasts = A::

Question 10

What tests can be done to diagnose ALL?

Answer 10

• medical history
• physical examination
• complete blood count
• blood smears
• bone marrow biopsy
• lumbar puncture (see if spina cord + brain have been invaded)
• kidney function, electrolytes and liver enzyme tests
• immunophenotyping

Question 11

What is immunophenotyping? What is the preferred method? Why is it beneficial in the diagnosis of ALL?

Answer 11

• lab technique used to identify proteins that are expressed on their cell surface
• preferred method = flow cytometry
• in malignant lymphoblasts there is expression of terminal deoxynucleotidyl transferase (TdT)
• can help differentiate is rom B or T cell lineage and the level of maturity of the WBCs

Question 12

What are the different stages in treating ALL? What is the aim of each stage?

Answer 12

1. remission induction
   - kill most tumour cells
   - reduce leukaemic blasts in bone marrow
2. consolidation/intensification
   - further reduce tumour burden
3. maintenance
   - kill any residual cells

Question 13

What types of drugs are used in the remission induction stage?

Answer 13

1. steroids (prednisolone or dexamethasone
2. vincristine
3. asparaginase
   * daunorubicin used in adult ALL

Question 14

What types of drugs are used in the consolidation/intensification stage?

Answer 14

1. vincristine
2. cyclophosphamide
3. cytarabine
4. daunorubicin
5. etoposide
6. thioguanine
7. mercaptopurine

CNS treatment: hydrocortisone, MTX and cytarabine

Question 15

What types of drugs are used in the maintenance stage?

Answer 15

1. daily oral mercaptopurine
2. weekly oral methotrexate
3. monthly 5-day course of UV vincristine and oral corticosteroid

Question 16

What biological therapy can be used in ALL, and why is it used?

Answer 16

1. tyrosine kinase inhibitors
   - usually used in patients with Bcr-Abl1+ ALL
2. Blinatumomab (CD19-CD3 bispecific mAb) - engages CD3 T cells with CD19 B cells, causing the T cells to kill the CD19 B cells

Question 17

What factors are favourable in terms of prognosis?

Answer 17

1. 3-5 y/o
2. Female
3. Caucasian
4. Absent organomegaly
5. Absent mediastinal mass
6. Absent CVS involvement
7. Low leukocyte count
8. Lymphoid cell type
9. early Pre-B cell lineage
10. Rapid response to treatment
11. time to remission <4 weeks