CML

Question 1

What is the characteristic pathophysiology of CML?

Answer 1

Philadelphia (Ph) chromosome

An abnormal chromosome 22 (t 9:22) that results in a constitutively activated tyrosine kinase

BCR-ABL protooncogene

Question 2

How does CML tend to present?

Answer 2

In 50s and 60s with non-specific symptoms like fatigue, fever, night sweats

Lots are diagnosed incidentally by FBC showing raised WBC in all cell lines

Often have splenomegaly

Question 3

How is CML definitively diagnosed?

Answer 3

Bone marrow biopsy/aspirate: allows review of percentages of blasts, promyelocytes, basophils and other haematological cell types for staging of phase as well as material for cytogenetics. Proportion of blasts and basophils help to categorise the phase of disease.

Marrow tends to be hypercellular with myeloid hyperplasia in chronic phase

Cytogenetic or FISH: find Philadelphia chromosome

Blood film: Immature and mature myeloid cells all at different stages of maturation

Question 4

What white cell is a prognostic marker for CML?

Answer 4

Basophil

Question 5

What are some baseline investigations you should do with CML?

Answer 5

U&E
LFT
Bone Profile
Mg
LDH & Urate
Metabolic Profile (Lipids, HbA1c)
Blood Borne Virus Screen

Question 6

What are the three stages of CML, how do they present and how long do they last for?

Answer 6

1. Chronic phase

> 85%) present in the chronic phase. Clinical features non-specific e.g fatigue, weight loss and night sweats. Without treatment lasts 3-5 years

2. Accelerated phase

Features more apparent and severe and more difficult to treat and outcomes worse. Untreated this phase lasts around 6-18 months.

3. Blast crisis

Resembles an acute leukaemia with the rapid expansion of blasts. Without treatment survival is typically a 3-6 months

Question 7

How can you tell the difference between the accelerated phase and blast crisis in CML?

Answer 7

Accelerated:

Blasts in blood or marrow 15–29%, or blasts plus promyelocytes in blood or marrow >30%, with blasts <30%
Basophils in blood ≥20%

Blast Crisis:

Blasts in blood or marrow ≥30%
Extramedullary blast proliferation, apart from spleen

Question 8

How is CML treated?

Answer 8

IT S CURABLE

First-line: Tyrosine kinase inhibitor, good response in chronic phase

Chemotherapy: Hydroxyurea or Interferon-alpha

Allogenic bone marrow transplant

Question 9

Give some examples of Tyrosine Kinase inhibitors used in CML and the side effects of these?

Answer 9

Imatinib: Side effects include nausea & vomiting, oedema, cramps, rashes, GI symptoms, headache and fatigue

Dasatinib: Can cause pleuro-pulmonary toxicity

Nilotinib: Side effects include cytopenias, headache, nausea, change in bowel habit, rash, pruritus, fatigue and derangement of LFTs. May cause prolonged QT

Question 10

How is CML management different between chronic and advance phase?

Answer 10

Chronic phase

Emergency cytoreduction with very elevated WCC at diagnosis (e.g. > 100 ×109/L)
Good oral hydration and allopurinol to reduce risk of TLS
TKIs
Allogenic SCT if failed initial TKI therapy

.
Advanced phase

All patients should be treated as part of a clinical trial
Second generation TKI with or without intensive chemotherapy
Allo-SCT offers potential cure in appropriate patients

Question 11

What is the prognosis with CML?

Answer 11

If newly diagnosed chronic phase CML have a near normal life-expectancy

Ages of 15-64: 90% 5-year survival

65 and older: 40% 5-year survival