ALL

Question 1

ALL commonly affects which age group? [1]

Answer 1

ALL is the most common childhood malignancy

Question 2

Describe the pathophysiology of ALL

Answer 2

Acute lymphoblastic leukaemia (ALL) affects one of the lymphocyte precursor cells, causing acute proliferation of a single type of lymphocyte, usually B-lymphocytes.

The precursor cell acquire specific chromosomal mutations, which leads to uncontrolled proliferation of lymphoblasts and evasion of immune surveillance

As a result, lymphoblasts infiltrate bone marrow and other organs. which restricts hematopoiesis and leads to bone marrow suppression.

Question 3

What is the most common cytogenetic feature seen in ALL?

t(4;11)
t(12;21)
t(9;22)
Hypodiploid karyotype
Hypodiploid karyotype

Answer 3

What is the most common cytogenetic feature seen in ALL?

t(4;11)
t(12;21)
t(9;22)
Hypodiploid karyotype
Hypodiploid karyotype

Question 4

ALL is commonly seen in which patient populations? [3]

Answer 4

Those with chromosomal abnormalities:
- Trisomy 21
- Klinefelter’s syndrome

Fanconi anaemia

Monozygotic twins

Question 5

The most widely accepted classification system of ALL is the WHO classification.

Describe this classification [3]

Answer 5

• B cell lineage (85% of cases)
• T cell lineage (10-15% cases)
• Rare cases of NK cell lineage (<1% of cases)

Question 6

Describe the typical presentation of ALL related to marrow failure [4]

Answer 6

Recurrent infections: neutropaenia

Thrombocytopenia:
* Petechiae
* Nose bleeds
* Bruising

Anaemia:
* Fatigue
* Breathlessness
* Angina
* Syncope

Question 7

Describe the typical presentation of ALL related to tissue infiltration [4]

Answer 7

Lymphadenopathy
- Persistent
- Painless
- Firm & Rubbery

Hepatosplenomegaly
- Can present with anorexia, weight loss or abdomen pain

Bone pain

Mediastinal mass (may result in SVCO)

Testicular enlargement

Question 8

[]- an uncommon presentation among those being first diagnosed, but more likely among patients with relapsing ALL (10%)

Answer 8

Testicular enlargement ( < 1 %) - an uncommon presentation among those being first diagnosed, but more likely among males with relapsing ALL (10%)

Question 9

Describe the FBC seen in a patient with ALL [3]

Answer 9

Thrombocytopaenia

Anaemic

WBC: low or high
- Low indicates lymphoblasts present that have not differentiated as recognisable WBC
- High indicates similar enough to WBC to be counted

U&Es; LDH; uric acid high
- Due to metabolic abnormalities
- TLS

Question 10

T-cell ALL is rarer than the B-cell form. It is said to typically present in which patient population? [1]

Describe two common presenting symptoms [2]

Answer 10

T-cell ALL is rarer than the B-cell form. It is said to typically present in adolescent males with lymphadenopathy or a mediastinal mass.

Question 11

What investigational tests should you perfom to assess for features of disseminated intravascular coagulation (DIC)? [2]

Answer 11

Coagulation screen and DDIMER

Question 12

What is the definitve diagnostic test for ALL? [1]

Answer 12

Bone marrow aspiration and biopsy
- Immunophenotyping is used to identify the lineage.

Question 13

All patients with ALL diagnosis have what investigation performed? [1]

Answer 13

Regardless of symptoms or signs of CNS involvement all children diagnosed with ALL have a lumbar puncture performed to evaluate for CNS involvement, given its association with negative prognosis, and receive prophylactic intrathecal chemotherapy.

Question 14

Why might a PBS appear normal in a patient with ALL? [1]

Answer 14

Findings on a peripheral smear may be normal if leukaemia is still confined to the bone marrow at the time of presentation.

Question 15

What is the threshold lymphoblast level in a PBS for ALL diagnosis? [1]

Answer 15

The most commonly accepted threshold for diagnosis is when lymphoblasts occupy >20% of bone marrow.

Question 16

What specific information does immunophenotyping help provide with regards to ALL? [1]

Answer 16

Through analysis of the surface antigens, this also determines whether the lymphoblasts are of B or T cell lineage.

Question 17

How would you differentiate ALL from Burkitts lymphoma? [2]

Answer 17

Through histology with the characteristic ‘starry sky’ appearance of highly proliferative cells with basophilic cytoplasm in BL.

Confirmation of Burkitt’s lymphoma involves identification of a mature germinal centre immunophenotype and cytogenetic features specific to Burkitt lymphoma cells

Question 18

How would you differentiate ALL from AML based off which parts of the body are implicated [2]

Answer 18

ALL has a predisposition for testicular, and CNS involvement

AML has a predisposition to involve skin and gums or other mucous membranes

Confirm AML through the presence of myeloid features and antigens and absence of any lymphoid antigens.

Question 19

How would you differentiate ALL from aplastic anaemia? [2]

Answer 19

distinguished from ALL by hypocellular bone marrow and the absence of any blast cells.

Question 20

Describe the overall goals of the different phases of ALL treatment [4]

Answer 20

Pre-treatment & supportive therapy phase
* Treating any infection, metabolic complication and if indicated giving a transfusion to stabilise the patient.

Induction chemotherapy
- goal to eradicate the presence of leukaemic cells to < 5% of blasts and to restore normal haematopoiesis.

Consolidation:
- Prevent the growth of leukaemia from any residual cells (known as a minimal residual disease (MRD)) and to prevent the development of drug resistance, by using numerous agents with multiple mechanisms of action.

Maintenance therapy
- prevent relapse

Question 21

Desribe how the pre-treatment & supportive therapy phase of ALL is performed [4]

Answer 21

For roughly 5-7 daysL
* Corticosteroids with or without another drug
* Hydration
* Allopurinol
* CNS prophylaxis is given intrathecally

This pre-phase helps reduce the risk of TLS

Question 22

Desribe how the induction chemotherapyphase of ALL is performed [1]

Answer 22

The selection of chemotherapy is dependent on a multitude of factors including age, Philadelphia chromosome status and the presence of CNS disease. Those with CNS disease require intrathecal chemotherapy and prophylactic therapy may be used in those without to reduce the risk of CNS relapse.

Question 23

Describe the regime usually used for maintenance therapy fr ALL

Answer 23

daily 6-mercaptopurine and weekly methotrexate

though there is considerable variation.

Question 24

Describe the regime usually used for consolidation therapy fr ALL

Answer 24

the goal is to prevent the growth of leukaemia from any residual cells (known as a minimal residual disease (MRD)) and to prevent the development of drug resistance, by using numerous agents with multiple mechanisms of action.

For those who don’t achieve a complete remission following induction, termed high-risk cases, ESMO guidelines advise allogeneic haematopoietic cell transplantation leads to better outcomes.

Question 25

Describe 4 complications of ALL [4]

Answer 25

Tumour lysis syndrome:
- significant metabolic disturbances arising from the rapid breakdown of malignant cells, normally after therapy has been initiated. It should be anticipated and when appropriate prophylaxis may be given with close monitoring and HDU/ITU availability if needed.

Neutropenic sepsis:
- characterised by fever and neutrophils < 0.5 (or expected to fall below 0.5). A medical emergency requiring early identification and management.

SVCO:
- patients may present with features of superior vena cava obstruction (e.g. dyspnea, facial swelling, cough) secondary to a mediastinal mass.

Chemotherapy side-effects:
- depends on the therapy and intensity, can be early (e.g. mucositis, nausea and vomiting, hair loss) or late (e.g. cardiomyopathy, secondary malignancies)

Question 26

Describe what is meant by L-asparaginase-related coagulopathy [1]

Answer 26

L-asparaginase-related coagulopathy - L-asparaginase is a chemotherapeutic agent which is becoming more widely used. The mechanism of coagulopathy and thrombosis is due to fibrinogen and anti-thrombin 3 depletion.