Chronic Myeloid Leukaemia

Question 1

What is chronic myeloid leukaemia?

Answer 1

Leukaemia that is almost exclusively an adult disease, accounting for 14% of all leukaemias. CML affects the myeloid cells, i.e. basophils, neutrophils and eosinophils.

Leukaemic cells retain ability to differentiate, and proliferation occurs without bone marrow failure

t (9;22) BRABL gene

Question 2

What is the natural progression of CML?

Answer 2

Chronic phase → aggressive/accelerated phase → blast phase/crisis.

Question 3

Which age range does CML most commonly occur in?

Answer 3

Between 40 and 60 years - disease is almost exclusively in adults

Question 4

What chromosomal abnormality is CML associated with?

Answer 4

Philedelphia chromosome t(9;22)

Question 5

What is the Phildelphia chromosome?

Answer 5

Hybrid chromosome comprising reciprocal translocation between the long arm of chromosome 9 and the long are of chromosome 22, forming a fusion gene BCR/ABL on chromosome 22, which has tyrosine kinase activity

Question 6

What symptoms can someone with CML present with?

Answer 6

• Tiredness
• Abdominal discomfort - splenomegaly
• Weight loss
• Fever, Night sweats
• Headache (occasionally) - hyperleucocytosis -> fundal haemorrhage and venous congestion
• Priapism - hyperleucocytosis
• Bruising, bleeding (uncommon)
• Gout - due to purine breakdown

Typically present incidentaly as increased WCC, low grade fever

Question 7

What signs might you see in someone with CML?

Answer 7

• Pallor - anemia
• Bruising
• Splenomegaly - often massive
• Lymphadenopathy
• Extramedullary soft tissue leukaemic deposit ‘chloroma’
• Retinal haemorrhage

Question 8

What is characteristic of the splenomegaly seen in CML?

Answer 8

It is often massive, causing abdominal discomfort

Question 9

What can ymphdenopathy in CML indicate?

Answer 9

Blast crisis

Question 10

What can retinal haemorrhage indicate in CML?

Answer 10

Leucostasis

Question 11

What investigations might you consider doing in someone with suspected CML?

Answer 11

• Bloods - FBC, U+E’s, LDH, Urate, Blood film, B12
• Imaging - None
• Specific - Bone marrow biopsy with cytogenetics, qPCR and FISH

Question 12

What does a chloroma indicate?

Answer 12

Blast crisis

Question 13

What are features of the chronic phase of CML?

Answer 13

Lasting months or years

• Few if any symptoms

Question 14

What are features of the accelerated phase of CML?

Answer 14

• Increasing symptoms
• Increasing spleen size
• Difficulty in controlling counts

Question 15

What are features of a blast crisis in CML?

Answer 15

Features of acute leukaemia +/- death

Question 16

What might you see on FBC in someone with CML?

Answer 16

• Normochromic normocytic anaemia
• WBC raised - usually >100 × 10⁹/L
  
  • All WBC types of myeloid cell line raised
• Platelets - low, normal or raised

Question 17

What might you see on blood film in someone with CML?

Answer 17

• Neutrophilia + whole spectrum of mature myeloid precursors.
• Elevated basophils and eosinophils
• Increased numbers of blasts

Question 18

What would elevated blast cells on blood film analysis indicate?

Answer 18

Accelerated phase/blast crisis

Question 19

What might you see on serum urate in someone with CML?

Answer 19

Increased Urate - due to purine breakdown

Question 20

What might you see on B12 blood tests in someone with CML?

Answer 20

Increased B12

Question 21

Why would you request FISH/PCR analysis when investigating CML?

Answer 21

Used to demonstrate the cytogenetic/molecular abnormality. These are also used to quantitatively monitor response to therapy.

Question 22

How would you manage someone with CML?

Answer 22

Tyrosine kinase inhibitors - Direct inhibitors of BCR-ABL fusion :

• Imatinib (Glivec)
• Dasatinib (Sprycel)
• Nilotinib (Tasigna)

Hydroxycarbamide

Allogeneic Transplantation - Only in TKI failures

Question 23

What are side effects of imatinib?

Answer 23

• Nausea
• Cramps
• Oedema
• Rash
• Headache
• Arthralgia

Question 24

What are the main chemotherapeutic medications used in CML?

Answer 24

Tyrosine kinase inhibitors

Question 25

When is it recommended that stem cell transplantation be used as first line treatment in CML?

Answer 25

Young adults

Question 26

How is myeloblastic transformation (blast crisis) treated?

Answer 26

Allogeneic stem cell transplantation

Chemotherapy rarely achieves lasting remission

Question 27

What proportion of CML patients have philedelphia chromosome?

Answer 27

>80%

Question 28

How would you distinguish between the spleen and a kidney on examination?

Answer 28

You can get above the kidney, but not the spleen.

Question 29

Prognosis of CML

Answer 29

5-6 years

There are 3 phases - chronic (lasting months or years wtih few, if any, symptoms, accelerated phase (increasing symptoms, spleen size and difficulty controlling counts), blast transformation (with features of acute lekaemia)