Page 213 - Essential Haematology

Chapter 14 Chronic myeloid leukaemia / 199

a year or two. In the majority, transformation is into splenomegaly. Cytogenetics are usually normal;
acute myeloid leukaemia (AML) or mixed types. the prognosis is variable.

These are more difficult to treat and survival is rare

beyond a few months. Imatinib is valuable in the Chronic e osinophilic l eukaemia
management of blastic transformation but resist-
ance to treatment usually occurs within a few Chronic eosinophilic leukaemia is a clonal persist-
9

weeks. New tyrosine kinase inhibitors aimed at ent eosinophilia ( > 1.5 × 10 /L). There may be an
overcoming resistance to imatinib include dasatinib interstitial lesion in chromosome 4 resulting in
and nilotinib (see p. 196 ). Allogeneic SCT may be FIP1L1 - PDGFRA fusion gene (in which case there
tried in younger subjects with an HLA - matching is a response to imatinib) or other less frequent

donor. cytogenetic or molecular defects. There may be

> 5% but < 20% blasts in the marrow. The cells may
infiltrate various organs causing damage (e.g.

Chronic n eutrophilic l eukaemia

endomyocardial fibrosis, lung, CNS, skin and gas-
These patients have no inflammatory or other causes trointestinal tract). If clonality cannot be shown and

of neutrophilia and no evidence for any other blasts are < 5%, the condition is diagnosed as hyper-

myeloproliferative disease. They may have mild eosinophilic syndrome (see p. 121 ).

■ Chronic myeloid leukaemia is a clonal ■ The clinical features include anaemia,
disorder of a pluripotent stem cell. The bleeding and splenomegaly. There is
disease accounts for around 15% of usually a marked neutrophilia with
leukaemias and may occur at any age. myelocytes and basophils seen in the
■ All cases of CML have a translocation blood fi lm. SUMMARY

between chromosomes 9 and 22. This ■ Transformation to an accelerated phase or
leads to the oncogene ABL1 being acute leukaemia may occur.
moved to the BCR gene on chromosome ■ Treatment is with tyrosine kinase inhibitors

22 and generates the Philadelphia such as imatinib, dasatinib or nilotinib.
chromosome. Tumour cells can acquire resistance to

■ The resulting chimeric BCR - ABL1 gene treatment and drug therapy is tailored in
codes for a fusion protein with tyrosine response to this.

kinase activity. ■ Stem cell transplantation can be curative

■ In most patients the Philadelphia and may also be useful for advanced

chromosome is seen by karyotypic disease.
examination of tumour cells but the ■ The clinical outlook is now very good and

molecular rearrangement may sometimes patients can expect long - term control of
only be detected by FISH or PCR. disease.

■ The disease can occur at any age but is ■ Chronic eosinophilic and neutrophil

most common between the ages of 40 and leukaemias are much rarer.
60 years.

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