Leukaemia

Question 1

Who is affected by ALL?

Answer 1

Children

Question 2

How common is ALL?

Answer 2

Most common malignancy of childhood

Question 3

What genetic conditions can pre-dispose to leukaemia?

Answer 3

Down’s

Kleinfelter’s

Question 4

Which virus can pre-dispose to leukaemia?

Answer 4

HLTV-1

Question 5

What is the most common gene abnormality in leukaemia? What type of leukaemia does it usually cause?

Answer 5

Philadelphia Chromosome- Proto-oncogene
Abnormal Chr22- reciprocal translocation between Chr9 + Chr22
Associated w/97% cases of CML

Question 6

Why does Myelodysplastic syndromes need monitoring?

Answer 6

Precursor to leukaemia

30% go on to AML

Question 7

How is Myelodysplastic syndrome managed?

Answer 7

<5% blasts in BM: Conservative (RBC & Platelet transfusion), EPO
>5% blasts in BM: Supportive care (elderly), Chemo, BM transplant (if <50yo)

Question 8

Who is usually affected by AML?

Answer 8

Middle aged/elderly

Question 9

What are the risk factors for acute leukaemia?

Answer 9

White
Males
Younger age
Radiation dose: Maternal X-ray when pregnant
Genetics: Down's

Question 10

How does ALL usually present?

Answer 10

RAPID onset BM failure:
Anaemia: Dyspnoea, pallor, lethargy
Thrombo: Bruising, purpura
Neutro: Infections 
Systemic: ↓weight, fever, malaise
Lymphadenopathy
BONE PAIN
SPLENOMEGALY
Testicular enlargement
Cranial nerve palsy

Question 11

How does AML usually present?

Answer 11

Marrow failure (anaemia, thrombocytopenia, neutropenia)
Systemic: ↓weight, fever, malaise
Bone pain
Violaceous skin lesions

Question 12

How is ALL investigated?

Answer 12

• Blood Film: LYMPHOBLASTS
• Bloods:↓Hb, ↓Plt ↓Neut,↑WBC (poor prog)
• BM Aspirate: ↓erythropoiesis ↓megakaryocytes (plt precursors) > 20% blasts
• Flow cytometry immunophenotyping: Tumour lineage (myeloid/lymphoid)
• CXR: Mediastinal widening

Question 13

How is AML investigated?

Answer 13

• Blood Film: AUER RODS, myeloid blasts
• Bloods: Bloods:↓Hb, ↓Plt ↓Neut,↑WBC (poor prog)
• BM Aspirate: ↓erythropoiesis ↓megakaryocytes (plt precursors) > 20% blasts
• Flow cytometry immunophenotyping: Tumour lineage (myeloid/lymphoid)

Question 14

How are Auer rods visualised?

Answer 14

Blood film w/myeloperoxidase stain

Question 15

How are ALL & AML differentiated between?

Answer 15

Auer Rods: YES = AML, NO = ALL 
Lymphoblasts: YES = ALL, NO = AML
Bone & joint involvement: YES = ALL, NO = AML
Hepatosplenomegaly: YES = ALL, NO = AML
Organ infiltration: YES = ALL, NO = AML

Question 16

What is the prognosis of untreated & treated acute leukaemia?

Answer 16

Untreated: Fatal within months
Treated: Approx 1 year

Question 17

What are the treatment options for acute leukaemias?

Answer 17

Palliative

Curative intent

Question 18

What are the 3 phases of ‘curative’ treatment for acute leukaemia?

Answer 18

1) Remission induction: Majority of tumour destroyed by induction chemo= BM hypoplasia (ICU admission as ↓↓WCC)
2) Remission consolidation: wait until normal haematopoesis → 3-4week cycle of chemo to attack remaining tumour cells, may include BM transplant AIM TO ACHIEVE COMPLETE REMISSION
3) Maintaining remission: Outpatient Tx for >3yrs THEN if ALL observe

Question 19

What are the options for palliative care in acute leukaemia?

Answer 19

Supportive: Control bleeding, Tx Sx of anaemia (RBC transfusion), Tx infections (prophylactic Abx & antifungals)

Question 20

What is the major difference in the treatment of ALL & AML?

Answer 20

ALL patients w/ALL get CNS treatment

Question 21

What is the prognosis like in ALL?

Answer 21

Kids = Very good
Complete remission is obtained in almost all
80% alive at 5years

Question 22

What is a high risk complication of BM transplant in leukaemia patients?

Answer 22

Graft vs Host disease

Question 23

What is the pathophysiology of ALL?

Answer 23

↑No of Lymphoid Blast cells push other cells out of bone marrow acutely → rapid onset of Anaemic, Neutropenic, thrombocytopenic Sx

Question 24

What is a complication of ALL?

Answer 24

Tumour lysis syndrome → Renal failure

Question 25

Who is usually affected by CLL?

Answer 25

Elderly

Question 26

Which cells are usually affected in CLL?

Answer 26

B lymphocytes

Question 27

What cells are affected in CML

Answer 27

Affects the myeloid cells: | Basophils, neutrophils and eosinophils.

Question 28

What is the natural progression of CML?

Answer 28

Chronic phase → Aggressive phase → blast phase (>20% blast cells)

Question 29

What is a blast crisis?

Answer 29

Acute terminal phase of CML Mortality↑↑↑ >20-30% blast cells in the blood or bone marrow

Question 30

What are the Sx of CML?

Answer 30

``` SOB Abdominal discomfort/splenic pain- splenomegaly Fever & Night sweats Lymphadenopathy Gout (↑cell turnover = ↑urate) Dyspnoea & cough ```

Question 31

What are the Sx of a blast crisis?

Answer 31

``` Rapid increase in proportion of blast cells Fever Bone pain Fatigue Splenomegaly Sx of anaemia Sx of thrombocytopenia ```

Question 32

What investigations are done for suspected CML?

Answer 32

Bloods: ↑WBC, Hb↓/n Blood Film: Neutrophilia w/myeloid precursors, LARGE white cells BM Aspirate: ↑↑no. of cells FISH: Find Philadelphia Chromosome

Question 33

How is CML managed?

Answer 33

Imatinib (stops BCR-ABL fusion)- continued indefinitely if needed. If used in aggressive disease → chronic disease Stem cell transplantation Autologous transplant

Question 34

How is CLL present?

Answer 34

Usually asymptomatic (incidental finding) Immunosuppression: Recurrent infections, anaemia Painless lymphadenopathy Splenic pain Hepatomegaly / splenomegaly++

Question 35

How is CLL investigated?

Answer 35

Blood: ↑↑WCC, Hb↓/n Blood Film: ↑lymphocytes, Smudge/Smear cells BM Aspirate: Similar to peripheral blood Cytogenetics

Question 36

How is CLL managed?

Answer 36

Chlorambucil +/- Prednisolone | Chemo