Haematology & Oncology

Chronic Myeloid Leukaemia (CML)

A single acquired fusion gene, BCR-ABL1 from the Philadelphia chromosome, creates a constitutively active tyrosine kinase that drives myeloid overproduction with preserved maturation, so the blood fills with maturing granulocytes and the spleen enlarges, usually indolently until it is controlled by a targeted inhibitor.

In a nutshell

CML is driven by the BCR-ABL1 fusion tyrosine kinase from the Philadelphia chromosome t(9;22). Maturation is preserved, so the blood fills with maturing granulocytes and basophils rather than blasts, and the spleen enlarges. A tyrosine kinase inhibitor (first-line imatinib) controls most patients, with molecular monitoring of BCR-ABL1.

Classic presentation

A middle-aged adult found to have a very high white cell count on a routine blood test, with a left-shifted granulocytosis, basophilia and splenomegaly.

Key points

The Philadelphia chromosome t(9;22) creates BCR-ABL1, a constitutively active tyrosine kinase that defines and drives CML.
Maturation is preserved: the film shows the full maturing granulocyte series with basophilia, not sheets of blasts.
Massive splenomegaly and constitutional symptoms are characteristic; many cases are found incidentally.
First-line treatment is a tyrosine kinase inhibitor such as imatinib, monitored by quantitative BCR-ABL1 transcripts.
CML is triphasic: untreated it progresses from chronic phase through accelerated phase to blast crisis, which behaves like acute leukaemia.

First-line investigation

Full blood count and blood film showing a left-shifted granulocytosis with basophilia, confirmed by cytogenetic and molecular testing for the Philadelphia chromosome and BCR-ABL1.

Management

Confirm the fusion and phase

Confirm BCR::ABL1, assess the blood film and phase, and review comorbidity and interactions with the specialist MDT.¹

Start TKI therapy

Use imatinib, dasatinib or nilotinib according to current NICE recommendations and specialist selection.^2,1,4

Monitor molecular response

Use serial quantitative BCR::ABL1 monitoring; investigate adherence, interactions and resistance if response is inadequate or lost.^1,5

Manage resistance or advanced phase

Escalate urgently for blast phase, rising blasts, clonal evolution or significant loss of response; consider later-line therapy and transplant through the specialist service.^1,5,4

Address long-term safety

Review TKI toxicity, cardiovascular risk, pregnancy plans, interactions and adherence, with clear safety-netting.^1,3,4

Exam traps

Basophilia with a left-shifted granulocytosis and splenomegaly points to CML, not a reactive leukaemoid reaction, which lacks the Philadelphia chromosome.
CML shows maturing granulocytes, not blasts; a rising blast count signals transformation to accelerated phase or blast crisis.
The Philadelphia chromosome also occurs in a subset of ALL, where it likewise adds a tyrosine kinase inhibitor, so it is not unique to CML.
A very high white cell count can cause leucostasis and priapism; do not dismiss it as simple infection.

Illustrations

Blood film in chronic myeloid leukaemiaPeripheral blood film showing marked leucocytosis with the full maturing granulocyte series and basophilia, without a blast excess.Paulo Henrique Orlandi Mourao, Wikimedia Commons · CC-BY-SA-3.0

Marked splenomegaly on CTCoronal contrast CT showing a markedly enlarged spleen, highlighted by arrows; massive splenomegaly is a characteristic clinical feature of chronic-phase CML.Hellerhoff; labels by Mikael HÃ¤ggstrÃ¶m, Wikimedia Commons · CC-BY-SA-3.0

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.