Chronic Leukaemias

Question 1

What is the difference, between CML and Myeloproliferative disorders and Myelodysplastic syndromes?

Answer 1

Overall: % of Blast in Bone marrow used to differentiate

1. Acute myeloid leukaemia (blasts >20%
2. Myelodysplasia (blasts 5-19%)
3. Myeloproliferative disorders (<5%, no increased blasts)

CML is an example of a myeloproliferative disorders

Question 2

What is the epidemiolgoy of CML?

Answer 2

Generally uncommon cancer of adults (median age 50, incidence infcreaseses in age)

Question 3

In what cells do mutations that cause CML usually occur?

Answer 3

Generally in pluripoitent lymphoid-myeloid stem cell

(Known from malignant transformation –> can transform into both, AML and ALL)

Question 4

What is the general prognosis of CML?

Answer 4

Before treatment 2-3 years at diagnosis

With treatment: 5 year survival 70-80%

Question 5

What genetic mutation/ abnormality is associated with the developmet of CML?

Answer 5

Strong association with Philadelphia t(9;22) chromosome –> causeing BrC-ABL1 fusion gene

Question 6

What is the common clinical progression of CML?

Answer 6

3 Phases
Chronic, Accelerative, Blast Crisis

In chronic phase ofen asymptomatic (20% diagnosed incidentally)
Otherwise

• splenomegaly (moderate - only becomes massive in acceleartive phase)
• potentailly B-symptoms (lymphadenoapthy not typical)

Question 7

What are the findings of an FCB in CML

Answer 7

1. WCC very high (due to precursors and increase in mature granuloytes incl increase in basophilia, eosiniphils (less likely to be confused with reactive)
2. Platelet: normal or high
3. Hb: normal or low

Question 8

How is CML diagnosed?

Answer 8

Typical FBC findngs
confirmation: cytogenetics (FISH or molecuilar analysis for BCR-ABL! fusion gene

BM biopsy rarely neede, but if donw shows hypercellular marrow

Question 9

What is the usual approach to treatment of CML?

Answer 9

Due to strong association with philadelphia chromosome —>
Usually ABL1 tyrosine kinase inhibitor (imatinib)

2nd line: switch to 2nd or 3rd generation Tyrosine kinase inhibitor

3rd line: allogenic stem cell transplant

Question 10

What is the epidemiology of CLL?

Answer 10

CLL is the commonest leukaemia in western world

More common in adults, incidence incrases with age

Male> Femlae (1.3:1)

Question 11

What cells are the amnormal cells in CLL?

Answer 11

Generally mature B -cells (analogues to antigen-experiences B-cells)

Question 12

What is the clinical presentation of CLL?

Answer 12

Often incidental diagnoss (due to lymphocytosis - CLL is commonest cause of lymphocytosis in adults)

More advances

• lymphadenopahty
• splenomegaly
• increases susceptibility to infection

Question 13

How is CLL treated?

What is the prognosis of CLL?

Answer 13

Rule of 3rds
1/3 never progress, 1/3 progress with good response to treatment, 1/3 progress and die from CLL

Often no treatment needed for 5-10 years
Then terminal phase (2-3 years til death)
* Rituximab (anti-CD20) + chemotherapy

+ supportive treatment

Can undergo malignant transformation (Richter Transformation in 5% of cases)

Question 14

What supportive treatment might be necessary in CLL?

Answer 14

1. Increased risk of infection (due to non-functinal B-cells) –> preventin
   Vaccination (influenza, pneumococci)
   early ABX + Zoster treatment
   Iv-Ig if IgG <5

Question 15

What are findings of CLL on FBC and blodo film?

Answer 15

FBC
1. Lymphocytosis (most common cause in adults)
2. Normocytic normochromic anaemia (BM infiltration or later on AIHA)
3. Thrombocytopenia

Film
**Smudge Cells/ Smear cells ** (ruptured mature lymphocytes)

Question 16

How can lymphocytosis due to CLL be differentiated from reactive lymphocyosis?

Answer 16

Immunophenotypig

CLL: monoclonal cells express either kappa or lambda light chains
Reactive: express both as polyclonal

Question 17

What markes indicate a CLL on Flow Cytometry?

Answer 17

Normal B-cell Markers (CD19,20 and 22)

often
1. CD 5+
2. CD 23+
(Both would ne negative in NHL)