Chronic Myeloid Leukaemia Flashcards
What is chronic myeloid leukaemia?
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
What is the natural progression of CML?
Chronic phase → aggressive/accelerated phase → blast phase/crisis.
Which age range does CML most commonly occur in?
Between 40 and 60 years - disease is almost exclusively in adults
What chromosomal abnormality is CML associated with?
Philedelphia chromosome t(9;22)
What is the Phildelphia chromosome?
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
What symptoms can someone with CML present with?
- Tiredness
- Abdominal discomfort - splenomegaly
- Weight loss
- Fever, Night sweats
- Headache (occasionally) - hyperleucocytosis
- Priapism - hyperleucocytosis
- Bruising, bleeding (uncommon)
- Gout
What signs might you see in someone with CML?
- Pallor - anemia
- Bruising
- Splenomegaly - often massive
- Lymphadenopathy
- Extramedullary soft tissue leukaemic deposit ‘chloroma’
- Retinal haemorrhage
What is characteristic of the splenomegaly seen in CML?
It is often massive, causing abdominal discomfort
What can ymphdenopathy in CML indicate?
Blast crisis
What can retinal haemorrhage indicate in CML?
Leucostasis
What investigations might you consider doing in someone with suspected CML?
- Bloods - FBC, U+E’s, LDH, Urate, Blood film, B12
- Imaging - None
- Specific - Bone marrow biopsy with cytogenetics, qPCR and FISH
What does a chloroma indicate?
Blast crisis
What are features of the chronic phase of CML?
Lasting months or years
- Few if any symptoms
What are features of the accelerated phase of CML?
- Increasing symptoms
- Increasing spleen size
- Difficulty in controlling counts
What are features of a blast crisis in CML?
Features of acute leukaemia +/- death
What might you see on FBC in someone with CML?
- Normochromic normocytic anaemia
-
WBC raised - usually >100 × 109/L
- All WBC types of myeloid cell line raised
- Platelets - low, normal or raised
What might you see on blood film in someone with CML?
- Neutrophilia + whole spectrum of mature myeloid precursors.
- Elevated basophils and eosinophils
- Increased numbers of blasts
What would elevated blast cells on blood film analysis indicate?
Accelerated phase/blast crisis
What might you see on serum urate in someone with CML?
Increased Urate - due to purine breakdown
What might you see on B12 blood tests in someone with CML?
Increased B12
Why would you request FISH/PCR analysis when investigating CML?
Used to demonstrate the cytogenetic/molecular abnormality. These are also used to quantitatively monitor response to therapy.
How would you manage someone with CML?
Tyrosine kinase inhibitors - Direct inhibitors of BCR-ABL fusion :
- Imatinib (Glivec)
- Dasatinib (Sprycel)
- Nilotinib (Tasigna)
Hydroxycarbamide
Allogeneic Transplantation - Only in TKI failures
What are side effects of imatinib?
- Nausea
- Cramps
- Oedema
- Rash
- Headache
- Arthralgia
What are the main chemotherapeutic medications used in CML?
Tyrosine kinase inhibitors
When is it recommended that stem cell transplantation be used as first line treatment in CML?
Young adults
How is myeloblastic transformation (blast crisis) treated?
Allogeneic stem cell transplantation
Chemotherapy rarely achieves lasting remission
What proportion of CML patients have philedelphia chromosome?
>80%
How would you distinguish between the spleen and a kidney on examination?
You can get above the kidney, but not the spleen.
