Acute Lymphoblastic Leukaemia

Question 1

What is acute lymphphoblastic leukaemia?

Answer 1

malignancy of B or T lymphoblasts characterized by uncontrolled proliferation of abnormal, immature lymphocytes and their progenitors (lymphoid progenitor and haematopoietic stem cell)
- leads to the replacement of bone marrow elements and other lymphoid organs

Question 2

What is pantocytopenia?

Answer 2

occurs when a person has a decrease in all three blood cell types
- erythrocytes, leukocytes and platelets

occurs as a result of the bone marrow’s reduced ability to produce normal blood cells

Question 3

Where are lymph nodes located?

Answer 3

neck (cervical lymph nodes)
groin (inguinal lymph nodes)
armpits (axillary lymph nodes)
abdomen
chest (medistinal)

Question 4

What are the signs and symptoms of acute lymphoblastic leukaemia?

Answer 4

signs
- neutropenia (low neutrophils), anaemia (low erythrocytes) and thrombocytopenia (low platelets)
= due to bone marrow suppression/myelosuppression

symptoms
- fatigue, flu like symptoms, fever, dyspnoea, paleness
- bruising and bleeding, repeated infections, swollen glands
- weight loss, bone pain,

Question 5

How can acute lymphoblastic leukaemia be diagnosed?

Answer 5

bone marrow aspirate (testing fluid sample)

lumbar puncture (testing cerebrospinal fluid)

Question 6

What does acute lymphoblastic leukaemia treatment depend on?

Answer 6

age
presenting white blood cell count
cytogenetics (study of the structure and properties of chromosomes)

Question 7

What are the steps in ALL treatment?

Answer 7

induction - 4 weeks = induce remission

consolidation - 4-8 weeks = eliminate residual cancer cells

interim maintenance I - 8 weeks = all steps below decrease relapse risk

delayed intensification - 8 weeks

+/- interim maintenance II - 8 weeks

maintenance - 1-2 years for girls and 3 years for boys (as cancer can hide in testes)

Question 8

What is remission?

Answer 8

Remission means that the signs and symptoms of your cancer are reduced due to cancer treatment

Remission can be partial or complete.
- partial
= cancer is present but tumour is smaller/reduced levels of cancerous cells
- complete
= cancer is undetectable

Question 9

What drugs are used in induction?

Answer 9

vincristine
PEG aspargase (asparaginase) intramuscular
intrathecal methotrexate
high dose dexamethasone (steroid)

Question 10

What is the mechanism of action of vincristine?

Answer 10

binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death
- stops microtubule polymerisation (anaphase)

Question 11

What are the side effects of vincristine?

Answer 11

constipation
alopecia (hair loss)
neuropathy (damage to the peripheral nervous system)

Question 12

What is the mechanism of action of PEG aspargase IM?

Answer 12

asparaginase enzyme hydrolyzes L- asparagine to ammonia and aspartic acid
- leads to the depletion of L-asparagine (essential amino acid)
- inhibit protein synthesis in tumor cells by depriving them of the amino acid asparagine

Question 13

What are the side effects of PEG aspargase? Why is it PEGylated?

Answer 13

allergic reactions can occur due to PEGylation
require increased liver function tests due to toxicity

PEGylated - increased half life which is useful as intramuscular formulation is painful to administer

Question 14

What is the intrathecal route?

Answer 14

injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF)

Question 15

What are the side effects of steroids?

Answer 15

increased appetite
hyperglycaemia - requires counting carbs
mood and behaviour changes
insomnia

Question 16

What drugs are used in consolidation?

Answer 16

cyclophosphamide
6 mercaptopurine (oral)
cytarabine

Question 17

What is the mechanism of action cyclophosphamide?

Answer 17

is an alkylating agent
- phosphoramide metabolite forms cross-linkages within and between adjacent DNA strands at the guanine N-7 position
- these structural modifications are permanent and eventually lead to programmed cell death.

Question 18

What is the most common side effect of cyclophosphamide? How can it be prevented?

Answer 18

haemorrhagic cystitis
- is inflammation and bleeding from the lining of the bladder
- caused by cleavage of cyclophosphamide into metabolite acrolein

• prevent it by hydrating patient pre, during and post treatment
• can take mesna (sodium 2-mercaptoethane sulfonate)

Question 19

What is the mechanism of action of 6 mercaptopuruine? What can you not take it with?

Answer 19

• is an antimetabolite
  = interferes with nucleic acid synthesis by inhibiting purine (A and G) synthesis and metabolism

it cannot be taken with dairy products
- dairy products contain xanthine oxidase which metabolise it and inactivate it

Question 20

What is the mechanism of action of cytarabine? What are the side effects?

Answer 20

antimetabolite and antineoplastic agent
- inhibits DNA polymerase
- is converted to cytarabine-5´-triphosphate, which is the active metabolite incorporated into DNA during DNA synthesis. This results in a cell cycle arrest in the S phase.

cause fevers
- makes it difficult to differentiate between infections and drug side effects

Question 21

What drugs are used for interim maintenance? What is the mechanism of action?

Answer 21

IV methotrexate

• antifolate antimetabolite
• inhibits dihydrofolate reductase (DHFR), an enzyme responsible for the conversion of dihydrofolate into tetrahydrofolate
• THF is needed for the synthesis of nucleotides required for DNA synthesis thus inhibition results in blockage of cell proliferation and growth.

Question 22

What are the side effects of methotrexate? What drugs interfere with it?

Answer 22

mucositis
- inflammation of the mucosa that line the mouth and GIT

penicillins reduce methotrexate clearance
- increases risk of toxicity

Question 23

What drugs are used during intensification? What is the mechanism of action?

Answer 23

doxorubicin
- intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair
- = introduces DNA strand breakages and prevents repair leading to cell death
- generation of free radicals and their damage to cellular membranes, DNA and proteins

Question 24

What are the side effects of doxorubicin? What monitoring is needed?

Answer 24

side effects
- cardio toxicity = arrhythmias, LV dysfunction or heart failure
- photosensitivity
- neutropenia

monitoring
- echocardiogram to look at left ventricular ejection fraction

Question 25

How should maintenance be carried out?

Answer 25

20 months
oral
- Mercaptopurinedaily
- Methotrexate weekly

injections
- Pulses of monthly dexamethasone and Vincristine

Question 26

What supportive care is needed in acute lymphoblastic leukaemia?

Answer 26

Weekend antibiotic prophylaxis
- co-trimoxazole (sulfamethoxazole and trimethoprim)

Flu vaccine/COVID vaccine
Transfusions
Neutropenic Sepsis

Question 27

What test is needed before starting fluorouracil or capecitabine?

Answer 27

dihydropyrimidine dehydrogenase (DPD) test
- check to see if levels are normal or deficient
- DPD is an enzyme which metabolises fluorouracil and capecitabine

if deficient then chemotherapy drugs can accumulate in the body and puts patients at risk for toxicity

Question 28

What factors increase the risk of a patient developing nausea and vomiting during chemotherapy?

Answer 28

Combined cancer therapies
Higher doses increase risks
Radiation therapy,

If a drug is a high risk drug that will also increase risk

Age and gender (younger (<50) and female),
If the treatment is long.
Nausea in previous chemotherapy

Female that experienced morning sickness
Tumour in GIT
Constipation
Co-prescribed opioids - natural nausea S/E
Active infection or sepsis
Kidney disease
Fluid and electrolyte imbalance

Question 29

What is the antiemetic regimen for high emetic risk cancer drugs?

Answer 29

day 1 - olanzapine, aprepitant, ondansetron and dexamethasone
day 2,3,4 - olanzapine, aprepitant and ondansetron

Question 30

What is the antiemetic regimen for moderate risk cancer drugs?

Answer 30

day 1 - ondansetron and dexamethasone
day 2,3 - ondansetron or dexamethasone

Question 31

What patients will not benefit from cetuximab?

Answer 31

Patients with colorectal tumor-bearing mutated K-ras but patients with wild type KRAS mutation do