23rd July 2024

Acute myeloid leukaemia

Background of AML

AML occurs due to clonal proliferation of haematopoietic precursor cells of myeloid lineage in the bone marrow.

In adults, it is the most common acute leukaemia and the second most common leukaemia. The median age of diagnosis is 65 years, with a male predominance.

The exact aetiology is unknown, however there are numerous associated risk factors:

• Environmental exposure to radiation and benzene
• Pre-existing haematological pathology such as myelodysplastic syndrome or myeloproliferative neoplasm
• Previous treatment with chemotherapy, particularly alkylating agents and topoisomerase II inhibitors

Presentation and diagnosis of AML

The proliferation of precursor myeloid cells (blast cells) in the BM leads to BM failure, causing:

• Anaemia: pallor, palpitations, dyspnoea, fatigue
• Thrombocytopenia: bruising, excess bleeding
• Neutropenia: infections

Gum hypertrophy can also be a presenting feature, seen most commonly in the monocytic subtypes of AML.

Diagnosis is multi-faceted:

• Blood tests: FBC (cytopenias); can include a metabolic panel to screen for tumour lysis syndrome (high potassium, low calcium, high phosphate, high uric acid)
• Blood film: immature myeloid blasts with pathognomonic Auer rods (Figure 1), ≥20% blasts
• BM biopsy: diagnosis if ≥20% blasts; carry out immunophenotyping to differentiate AML from ALL (see acute lymphocytic leukaemia); cytogenetic and molecular analysis for prognostication and classification

Tumour lysis syndrome occurs due to the rapid breakdown of a large number of cancer cells. This occurs most commonly a few weeks after treatment initiation but can also occur spontaneously. A high phosphate is not seen as commonly in spontaneous tumour lysis syndrome, compared to post-treatment.

Image Source: Wikimedia Commons (2010). Myeloblast with Auer rod smear 2010-01-27, Licensed under a creative commons licence. Available for free at: https://en.wikipedia.org/wiki/Auer_rod#/media/File:Myeloblast_with_Auer_rod_smear_2010-01-27.JPG (Accessed: 16 January 2024)

Management and prognosis of AML

Full treatment for AML in medically fit and willing patients consists of two stages:

1. Remission induction: generally carried out with cytarabine and an anthracycline (e.g. daunorubicin)
2. Consolidation therapy: often carried out with high dose cytarabine

Allogeneic haematopoietic stem cell transplantation (SCT) can be used in patients with an intermediate or poor prognosis in addition to consolidation therapy, especially in patients <60 years old.

Less intensive chemotherapy options are available for patients not likely to tolerate high intensity regimes. These are less likely to induce complete remission and allow long-term disease control.

Maintenance chemotherapy is generally not used.

Various parameters are used for prognosis:

Acute promyelocytic leukaemia

Acute promyelocytic leukaemia (APL) is a subtype of AML. Peak incidence is in early adulthood. The vast majority of cases are caused by t(15;17) causing formation of the PML-RARα fusion gene.

APL is a medical emergency that warrants quick diagnosis and treatment as it can result in (and often presents with) disseminated intravascular coagulation or haemorrhage, which has high mortality.

Treatment is with all-trans-retinoic acid with an anthracycline for induction remission. Consolidation therapy uses the same combination of chemotherapy.

APL has a good prognosis with >80% cure rates.