Chronic Myeloid Leukaemia

Clinical context

A 66 year old female undergoing routine pre operative assessment

At a glance

StainMGG

About Chronic Myeloid Leukaemia

This blood film is of Chronic Myeloid Leukaemia (CML). CML is classified on diagnosis as to whether it is in the chronic phase - i.e. slow growth, accelerated phase - when things start to move faster and the condition needs more urgent attention, or blast phase, when the CML has effectively transformed into acute leukaemia. The chronic phase part is often followed by a number which determines whether someone has ever been in accelerated or blast phase, and then with treatment has returned to chronic phase. The vast majority of people with CML that you see will be CML-CP1. 

In the blood film, you can see almost every stage of white cell maturation. CML patients typically have a high to very high white count - sometimes running to several hundreds. A large proportion of these will be normal looking mature neutrophils. These neutrophils are not normal - they all contain the abnormal driver of CML, the fusion gene between BCR and ABL1. This is also called t9:22 - a translocation between chromosome 9 and 22. The ABL1 gene is normally on chromosome 9 (at band 9q34), and the BCR gene is normally on chromosome 22 (at band 22q11). When these cross over, you get the Philadelphia chromosome which is a t(9;22)(q34;q11). So you can detect this with PCR - looking for the gene, FISH - looking for the fusion or Cytogenetics - looking for the chromosome. 

The blood film also has significant left shift, with numerous myeloid precursors. There will be blasts, but these should not be prominent ad certainly should be less than 10%. If you have more than 10% blasts or basophils, you may be looking at accelerated or blast phase. Call for immediate senior review if you are worried about that. There are two characteristic findings on a CML blood film. One is basophilia - there should usually (but not always!) be noticeable basophilia. In this film, basophils are absent. This should always make you consider cryptic mutations. The mutation here was a standard Bcr-Abl1, just with no basophils. The second finding is a myelocyte peak. This means that when you do a differential, you see few bast, very few promyelocytes, lots of myelocytes, few band forms and lots of neutrophils. So there are two peaks on the differential. 

CML may also be associated with thrombocytosis with platelet anisocytosis, or anaemia. Usually the patient presents with symptoms of splenic enlargement, or hyperviscosity from the white cell count. CML is a haematological emergency, and the on call haematologist should be alerted.   

Morphological features

Morphologically normal Neutrophils

These neutrophils are morphologically normal. The reality is that they likely carry a t9:22, so are not normal, but under the microscope they do look like normal neutrophils. They will be significantly increased in number in CML.

Myelocytes

These are myelocytes. These are immature myeloid cells (bt not blasts or promyelocytes) and show a partial maturation arrest where some cells cannot move past the myeloid stage. The myelocyte peak in the differential is characteristic of CML. In normal blood or one marrow, there are few blasts, occasional promyelocytes, and so on until frequent neutrophils. In CML there are few blasts, plentiful myelocytes, few band forms and plentiful neutrophils.

Monocyte

A normal looking monocyte.

Giant platelet

This one may even be a megakaryocyte fragment as it is a little larger than the red cells around it. Abnormal platelets are a feature of CML as it is an MPN.

Blast

Blasts are a feature of CML, although they should not be frequent in chronic phase

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