Acute Lymphoblastic Leukaemia

Question 1

What is it a malignancy of?

Answer 1

Lymphoid cells affecting B or T lymphocyte cell lineages, arresting maturation and promoting uncontrolled proliferation of immature blast cells, with marrow failure and tissue infiltration

Question 2

When does it mainly occur?

Answer 2

Mainly a disease of childhood - peak incidence = 2 to 5

Male more than female

Question 3

What causes it?

Answer 3

No identifiable cause in most cases
Ionising radiation e.g x ray during pregnancy
Past chemotherapy
Genetic conditions: Down’s syndrome, Fanconi anaemia, neurofibromatosis type 1
Smoking
Weakened immune system e.g HIV

Question 4

The monoclonal proliferation looses the ability to differentiate, while retaining ability to…

Answer 4

Replicate

Question 5

What do the blasts do?

Answer 5

Replace BM cells - crowd out normal haematopoiesis
Enter peripheral blood
Metastasise throughout body - esp liver, spleen, LNs, testes, skin, mediastinum

Question 6

Are the onset of signs and symptoms slow or abrupt?

Answer 6

Abrupt

Question 7

What signs and symptoms are associated with ALL?

Answer 7

Marrow failure:
Anaemia- fatigue, pallor, SOB
Low WCC - Frequent infections
Thrombocytopenia- bleeding gums, epistaxis, petichiae, purpura, blood in urine/stool

Infiltration:
Hepatosplenomegaly
Lymphadenopathy (painless) - superficial or mediastinum
Orchidomegaly

Fever, weight loss, night sweats
Bone pain
Airway obstruction - mediastinal or thymic infiltration
If CNS involved - meningism, CN involvement, seizures, nausea

Question 8

What common infections can occur?

Answer 8

Especially chest, mouth, perianal, skin
Sepsis
Zoster, CMV, measles, candidiasis, pneumocystis pneumonia

Question 9

What does FBC typically show?

Answer 9

Raised WCC usually
Anaemia
Thrombocytopenia

Question 10

What does peripheral blood film show?

Answer 10

Large blast cells

Question 11

What does bone marrow and aspiration show?

Answer 11

More than 20% blasts

Question 12

Why is flow cytometry done?

Answer 12

Confirm lineage - myeloid or lymphoid

Question 13

Why should a CXR be done?

Answer 13

Look for mediastinal widening

Question 14

Why should a LP be performed?

Answer 14

Check for CNS involvement

Question 15

What genetic test can be done?

Answer 15

FISH - examine chromosome number and translocations

PCR sequencing of DNA mutations

Question 16

In chemotherapy regime, the choice of agent depends on…

Answer 16

Cytogenetics

Question 17

Describe the chemotherapy regime

Answer 17

Induction e.g vincristine, prednisolone
Consolidation - high-medium-dose therapy in blocks over several weeks
CNS prophylaxis e.g intrathecal methotrexate +/- irradiation
Maintenance- prolonged chemotherapy for 2 years

Question 18

What supportive management is often required?

Answer 18

Blood/ platelet transfusion
IV fluids
Allopurinol / rasbucase to prevent TLS 
Antiemetics e.g ondansetron 
Monitor for infections - check oropharynx, skin, catheter sites regularly

Question 19

Describe the blast appearance

Answer 19

No granules
Increased nucleus to cytoplasmic ratio
Nucleolus less prominent than in myeloid blasts

Question 20

Describe T cell ALL

Answer 20

Typically occurs in young adults
Mass in mediastinum - pleural effusion, respiratory distress, SVCO
CD3+ and CD7+

Question 21

What types of ALL are there?

Answer 21

Pre B cell ALL
B cell ALL
T cell ALL

Question 22

Describe pre B cell ALL

Answer 22

Common in children, especially Down syndrome
CD10+, CD19+, CD20+
T(9;22) = bad prognosis
T(12;21) = good

Question 23

What are some unfavourable prognosticators?

Answer 23

Age > 60
WBCs > 100,000
Mature B or early T types
Philadelphia chromosome t(9:22)

Question 24

Will pre B cell with t(12:21) have a good response to chemotherapy?

Answer 24

Yes in 80% there is a cure

Question 25

Why might there be macrocytic anaemia?

Answer 25

Low folate levels due to rapid cell turnover

Question 26

ALL is the most common type of leukaemia that affects children. True or false?

Answer 26

True

Question 27

What is the role of remission induction?

Answer 27

Reduce blast cells into undetectable levels

Restore normal marrow function

Question 28

Why is consolidation necessary?

Answer 28

Relapse occurs in almost 100% of cases

Question 29

What should happen before chemotherapy?

Answer 29

Stabilise patient
If they have thrombocytopenia give platelets
If fever and granulocytopenia - blood culture and antibiotics
If leukostasis - leukopharesis

Prevent TLS - hydrate and give allopurinol

Question 30

In terms of management, what can be done as last resort?

Answer 30

BM transplant

Question 31

If patient has Philadelphia chromosome, what treatment can they have?

Answer 31

A tyrosine kinase inhibitor - imatinib

Question 32

What complications can occur due to treatment?

Answer 32

Chemotherapy - TLS leading to AKI
Direct testicular radiation - permanently low testosterone, consider sperm banking
Intrathecal radiation and RT - neurocognitive dysfunction