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Chronic myeloid leukaemia 

Chronic myeloid leukaemia

Chapter:
Chronic myeloid leukaemia
Author(s):

Tariq I. Mughal

and John M. Goldman

DOI:
10.1093/med/9780199204854.003.220306_update_001

Update:

This chapter has been substantially updated, in particular with regard to to the continued medical success in the treatment of patients with CML and the challenges in the optimal selection of first-line therapy and monitoring, and the current understanding of the cellular and molecular biology of CML.

Updated on 30 May 2013. The previous version of this content can be found here.
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date: 27 March 2017

Chronic myeloid leukaemia has a worldwide incidence of 1 to 2 per 100 000 population. Most cases are caused by translocation of the distal end of chromosome 9 on to chromosome 22 (known as a Philadelphia chromosome), which leads to the creation of a fusion protein expressed from the fusion gene formed by juxtaposition of parts of the BCR (break-point cluster region) and ABL1 genes. The resulting oncoprotein is a constitutive tyrosine kinase and appears to operate as an initiator for the development of the leukaemia. Why this translocation occurs is not known.

Clinical features, diagnosis, and (historical) prognosis

Clinical features—many patients are asymptomatic at diagnosis, which is made following a routine blood test. Others present with signs and symptoms including fatigue, sweats, fever, weight loss, haemorrhagic manifestations, and abdominal discomfort (due to splenomegaly).

Diagnosis—this is typically made by the examination of a peripheral blood film (revealing features including increased numbers of neutrophils and myelocytes) and the demonstration of the Philadelphia chromosome by conventional cytogenetics in a bone marrow aspirate sample. PCR analysis of peripheral blood or marrow confirms the presence of a BCR-ABL1 transcript and characterizes the BCR-ABL1 junction.

Prognosis—before the introduction of tyrosine kinase inhibitors (see below) the condition, having usually been diagnosed in the chronic phase, then spontaneously progressed after (typically) 3 to 6 years to myeloid (or less commonly lymphoid) blast transformation, which had very poor prognosis.

Treatment

The original tyrosine kinase inhibitor (TKI), imatinib, has had a very significant impact on the first line management of patients with chronic myeloid leukaemia (CML). It induces durable complete cytogenetic responses in the majority of patients and prolongs overall survival substantially. The drug, however, does not totally eradicate the leukaemia in most cases and therapy is usually life-long. Patients with sub-optimal responses to imatinib can be offered (1) newer TKIs, such as dasatinib, nilotinib, ponatinib and bosutinib; or (2) allogeneic stem cell transplantation (allo-SCT)—for patients less than 65 years of age and with a suitable donor.

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