Leukaemia 🩸🩸

Question 1

Acute Myloid Leukeamia (AML)

Mostly in which age and gender?
Survival %?

Answer 1

Older population (64 years)
More in MEN
Life risk 0.5- 30% survival

Question 2

Subtypes of Acute Myloid Leukeamia AML x4
Name and describe

Answer 2

1. De Novo AML:
   No risk factors
2. Secondary AML: progressed from another myeloid malignancy
3. Therapy Associated AML: occurred following previous chemotherapy or extreme radiotherapy
4. Familial AML: inheritable mutation that predisposes AML

Question 3

Clinical presentation of Acute Myloid Leukeamia AML 3

Answer 3

1. Infection, sepsis = decreases white blood cells
2. Fatigue, Shortness of breath = decrease red blood
3. Bruising, perechiae, bleeding = decreased platelets

Question 4

AML

medication to treat

Answer 4

Azacitidine

Question 5

Azicitidine

Moa

Side effects tolerable?

Answer 5

DNA methyltransferasw inhibitor
Reserves methylation induced silencing of tumour suppressor genes

Side effects are tolerable

Question 6

Molecular target in AML

Midostaurin

MOA

SIDE EFFECTS

Answer 6

FLT3 inhibitor

FLT3 receptor is mutated in 30% of AML

Side effects: higher anaemia and rash

Question 7

Acute Lymphoblastic Leukaemia ALL

More common in…?

Subtypes of ALL

Answer 7

Paediatrics, second incident peak in elderly

Separates into B cell and T cell subtypes

Question 8

Acute Lymphoblastic Leukaemia ALL

Clinical presentation?

Answer 8

Same as AML, but may have
Enlarged lymph nodes, higher risk of CNS involvement

Question 9

Acute Lymphoblastic Leukaemia ALL

Fit for chemotherapy:

Answer 9

1. High dose chemo
2. If CD20+ then ADD Rituximab
3. If Philadelphia Chromosome +ve = add TKI
4. ALLOGENIC STEM CELL TRANSPLANT for high risk patients

• aim to cure

Question 10

Acute Myloid Leukaemia

Fit for intensive chemotherapy….

Answer 10

1. High dose chemo - cytarabine + anthracycline
2. Add midostaurin IF FLT3 MUTATION POSITIVE
3. ALLOGENEIC STEM CELL TRANSPLANT IF HIGH RISK

*AIM TO CURE

Question 11

Relapse Acute Lymphoid Leukaemia

Treatment? 2

Answer 11

1. Blinatumomab = BITE therapy
2. Chimeric Antigen Receptor T-cells (CAR-T)

Question 12

Blinatumomab - BITE therapy

Answer 12

Bi-specific T-cell engager antibody construct (BITE)

Binds simultaneously CD3 cytotoxic t-cells to CD19 positive Leukaemia B cells.

Question 13

Chimeric Abtigen Receptor T cell (CAR-T) process

Moa

Answer 13

Engineered receptors that direct the T cells against tumour cells.

Once re-infuses in the patient, the Tcells entrants, proliferate and kill the tumour cells and also promote surveillance.

Question 14

Side effects of CAR-T cells and BITES

Answer 14

1. Cytokine release syndrome (CRS) =
   INFLAMMATORY STATE driven by cytokines released by CAR-T
   ie
   Fever, flu like symptoms,
   Rapidly leading to hypotension, shock, cardiac arrest.
2. Neurotoxicity

Question 15

How to manage the side effects of CART and BITES

Answer 15

1. CYTOKINE RELEASE SYNDROME
   = tocilizumab
2. Neurotoxicity
   = dexamethasone

Question 16

Chronic Myeloid Leukaemia:

Stat’s?

Answer 16

Age 50-60

Predicted to be most common Leukaemia by 2050

Most patients have normal life span

Question 17

Chronic Myeloid Leukaemia:

Prognosis

Answer 17

Asymptomatic

May have large spleen = causes early satiety

Question 18

Chronic Myeloid Leukaemia:

Diagnosis

Answer 18

1.FBC have overall increase in myeloid blood cells (neutrophils, basophils, eosinophils

2. Genetic testing to show part of Chromosome 9 and 22 joined (translocated) = results in creation of BCR-QBL1 gene

Question 19

What is the Philadelphia Chromosome?

Answer 19

Translocation of abl on chrom 9 to brc on chrom 22= formation of brc-abl fusion transcript.

The brc-abl transcript produces the oncogenic tyrosine kinase.

Question 20

Chronic Myeloid Leukaemia:

Treatment

Answer 20

1. Must treat with TYROSINE KINASE INHIBITORS

*Resistance to TKi may need allogenic stem cell transplant

Question 21

Chronic Myeloid Leukaemia:

Treatment of chronic phase
First line NAMES

Answer 21

Imatinib
Dasatinib
Nilotinib

Question 22

Is ponatinib first line for
Chronic Myeloid Leukaemia ?

Answer 22

No. It is a 3rd generation TKI =
Reserved for RESISTANT/REFRACTORY DISEASE.

Question 23

What are the interactions with Dasatinib?

Answer 23

Avoid PPI, H2A

antacids need a 2 hour gap (so does nilotinib)

Question 24

If patients reach deep remission (<0.01% bcr-abl) can they stop TKI?

Answer 24

Yes. If on them for long enough (3-8 years)

50% relapse
50% do not

Question 25

Chronic lymphocytic Leukaemia (CLL)

Diagnosis

Answer 25

High lymphocyte count
Blood film- smudge cells

Question 26

Chronic lymphocytic Leukaemia (CLL)

Treatment of
1. Asymptomatic
2. Symptomatic
3. Relapse, refractory

Answer 26

1. Asymptomatic = no Treatment
2. Symptomatic =
   Older and unfit > venetoclax-obinutuzumab
3. Relapse = brutons kinase inhibitor > ibrutinib or acabrutinib

Question 27

Chronic lymphocytic Leukaemia (CLL)
Relapse CLL trearment:

Ibrutinib
-MOA
-S,E

Answer 27

BRUTONS TYROSINE KINASE INHIBITOR Moa- CLL cells relies on BTK signal for survival and cell division

S/e:
Bleeding
Cardiac issues - AF, Hypertension,
Frequent infections

A major substrate for CYP3A4

Question 28

Chronic lymphocytic Leukaemia (CLL)

Which drug is more selective than ibrutinib as a BTK inhibitor?

Answer 28

Acalabrutinib

Question 29

Chronic lymphocytic Leukaemia (CLL)

Venetoclax -

Moa
S/e

Answer 29

bcl-2 (b-cell lymphoma) Inhibitor

S/e: tumour lysis syndrome

Take at same time every day with food

Major CYP3A4 substrate

Question 30

Leukaemia summary