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Acute myeloid leukaemia 

Acute myeloid leukaemia

Chapter:
Acute myeloid leukaemia
Author(s):

Jonathan Kell

, Steve Knapper

, and Alan Burnett

DOI:
10.1093/med/9780199204854.003.220304
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date: 25 April 2017

It is believed that acute myeloblastic leukaemia arises in a haematopoietic stem cell as a result of mutations which promote growth or inhibit apoptosis arising in association with mutations that inhibit differentiation. In most cases there is no obvious cause, but exposure to chemical and ionizing radiation may be relevant, including previous chemotherapy for solid tumours.

Clinical features and diagnosis

Clinical features—typical manifestations are those of marrow failure, most commonly symptoms and signs of anaemia and of bleeding (petechiae, purpura, from mucous membranes). Acute promyelocytic leukaemia is a medical emergency characterized by bleeding and disseminated intravascular coagulation.

Diagnosis—the key investigations are examination of peripheral blood and bone marrow for blast cell infiltration, with classification and prognosis of disease depending on morphology, immunophenotyping, karyotyping, and definition of particular molecular mutations.

Treatment and prognosis

General approach—aside from providing appropriate supportive care, the first clinical decision to be made in an individual patient is whether to undertake conventional intensive chemotherapy aiming for disease eradication, or to adopt a more palliative approach. Intensive chemotherapy is the norm up to age 60 years, but the biology of the disease tends to be less favourable above this age (e.g. more adverse cytogenetic abnormalities and expression of multidrug resistance genes), and patients develop comorbidities and become less generally fit.

Initial chemotherapy—(1) Intensive chemotherapy—this typically involves the combination of daunorubicin and cytosine arabinoside (cytarabine, ara-C), which achieves complete remission in 40 to 80% of cases, followed by consolidation chemotherapy comprising a second course of induction treatment and then courses of ara-C with or without additional agents (e.g. amsacrine, etoposide, mitoxantone). (2) Less-intensive chemotherapy—most often comprises hydroxycarbamide (hydroxyurea) or low doses of ara-C. (3) Acute promyelocytic leukaemia—this is exquisitely sensitive to all-trans-retinoic acid, which is given concurrently with chemotherapy.

Relapsed disease—more than 50% of patients will ultimately relapse and their overall outcome is generally very poor. The only curative option is allogeneic bone marrow transplantation if a second complete remission can be achieved with reinduction chemotherapy

Prospects for the future

Increasing knowledge of the underlying biology may allow treatment with small molecules that inhibit the effects of the more common molecular mutations. However, unlike chronic myeloid leukaemia (which is characterized by a single molecular abnormality), a single inhibitor is not going to offer corrective therapy.

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