Introduction

Acute myeloid leukaemia (AML) is a malignant clonal disorder of haematopoietic progenitor cells. Leukaemic transformation usually occurs at a very early stage of myeloid development, probably at or near the haematopoietic stem cell, but it may develop in a more mature cell. The disease is heterogeneous. The malignant cells acquire genetic alterations which upset their normal mechanisms of self-renewal, proliferation and differentiation. Ultimately the malignant clone causes marrow failure. AML is rare in childhood and the incidence increases with age; two-thirds of cases occur in people aged over 60 years.

Classification

The WHO system has now largely superseded the French-American-British (FAB) classification. The newer classification reduces the bone marrow leukaemic blast cell percentage differentiating AML from myelodysplastic syndrome (see p. 50) from 30% to 20%. Other key changes include the creation of specific subtypes with non-random cytogenetic or equivalent molecular abnormalities, and the distinction of patients with multilineage dysplasia and also previous chemotherapy. The major FAB subtypes are included in the ‘other’ category with the exception of acute promyelocytic leukaemia (previously FAB M3) which is now in the ‘recurrent translocations’ group due to the inevitable presence of t(15;17). It can be seen (Table 20.1) that occasional cases of AML show megakaryocytic or erythroid differentiation. Gene mutations are likely to become increasingly important in classification.

Clinical features

In practice there is little uniformity in presentation. Some patients are remarkably asymptomatic while others are seriously ill. Bone marrow infiltration by leukaemic blast cells usually leads to anaemia, neutropenia and thrombocytopenia. Thus, patients often have symptoms of anaemia, infection and haemorrhage.

One subtype of AML deserves special consideration as it must be treated as a medical emergency:

Tissue infiltration is more common in subtypes with monocytic morphology and immunophenotypic features (i.e. FAB M5) – patients often present with gum infiltration (Fig 20.1), lymphadenopathy, skin deposits and hepatosplenomegaly. Central nervous system (CNS) disease is rare in AML but most frequent in monocytic/monoblastic leukaemia.

Diagnosis

Diagnosis depends on a logical sequence of tests.

Management

Prognosis

The major factors determining outcome are age, initial response to treatment and genetic abnormalities. Approximately 80–90% of younger patients will achieve a CR with conventional chemotherapy. Younger patients with ‘standard risk’ disease have 5-year survivals of 40–45% with optimal therapy; this compares with around 70% for ‘good risk’ and 20% for ‘poor risk’ groups. Older patients have a greater incidence of adverse cytogenetics (Fig 20.3) and tolerate chemotherapy less well, and CR and cure rates are much lower (see p. 93). Indeed, it may be kinder not to use chemotherapy in some elderly patients. In children, intensive chemotherapy gives 5-year survival rates of around 50%.