Acute Myeloid Leukaemia

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Acute myeloid leukaemia (AML) is a haematological malignancy of clonal proliferation of early precursor myeloid-line cells. These cells lack the ability to differenitate into mature cells and result in an accumulation of immature blast cells in the bone marrow that spill into the peripheral blood. Anaemia, neutropaenia and thrombocytopaenia occur with the infilration of the marrow. The malignancy is often aggressively treated and cured but in cases where the patient is too old and frail for treatment, or where treatment has failed, the illness is invariably rapidly fatal and involvement from the local palliative care team is often sought by the haematology team.

Pathogenesis and Epidemiology

Although AML is the most common acute leukaemia, it is relatively rare overal with an average incidence of 5 cases per 100,000 people per year. In children, most acute leukaemias are acute lymphoblastic leukaemia.

AML is slightly more common in males and the average age of diagnosis is 65, although it does occasionally occur in young adults.

Risk factors for AML include exposure to previous radioation or cytotoxic drugs, various genetic abnormalities (e.g. it is more common in Down's syndrome) and other haematological disorders (e.g. myelodysplasia).

Clinical Features and Complications

AML is usually associated with features of cytopaenias including

  • Fatigue, dizzines and dyspnoea due to anaemia
  • Brusing, epistaxis and other bleeding due to thrombocytopaenia
  • Infections due to neutropaenia

Pain is uncommon although some patinets experience back, rib and sternal bony pains due to the infiltration and expansation of the marrow with blasts.

Fever and sweats are common and are usually due to infection. A few patients develop a fever directly due to the leukaemia.


In addition to petechiae and larger bruises, occasionally leukaemic cells infiltrate the skin. This is known as leukaemia cutis and is manifest by discrete palpable skin lesions. At other times, acute neutrophilic dermatosis (Sweet's syndrome) develops, which is an inflammatory condition where localized infiltrates of neutrophils occur in the skin.


Arthraglias sometimes occur in AML. Additionally, very occasionally joint pain and swelling occurs due to direct infiltration of the synovium by leukaemic cells. Gout is common due to break-down of tumour cells increasing urate levels.

Metabolic disturbances

The high cell break-down may result in tumour lysis syndrome which is manifest by

  • High phosphate
  • Low calcium
  • High urate
  • High potassium
  • Hyperviscosity and leukostasis

With very high circulating blasts, symptoms of poor blood flow through the brain (causing confusion or drowsiness) and lungs (causing dyspnoea) are common. This is termed leukostasis.

Diagnosis and Investigations

The diagnosis of acute myeloid leukaemia is usually made by examination of the blood film and a bone marrow biopsy. The current World Health Organization diagnostic criteria include a requirement for myeloid blasts to account for more than 20% of the bone marrow. The diagnostic criteria and classification of different types of AML is complex and evolving and involves cytogenetic and molecular genetic analysis. AML is often classified in one of 4 main types, with further sub-types in each category that have implications for treatment and prognosis:

  • AML with recurrent genetic abnormalities (10% of cases)
  • AML with myelodysplasia-related features (5% of cases)
  • Therapy-related AML and MDS (< 5% of cases)
  • AML, not otherwise specified (80% of cases)

In terms of palliative and supportive care, key investigations that may be helpful include:

  • Haemoglobin as blood transfusions may help symptomatic anaemia
  • Platelet count as the bleeding risk greatly increase once the platelet count drops below 10
  • White cell count as neutropaenia increases the risk of infection and a rapidly rising peripheral blast count indicates that death may be within days or weeks (see leukostasis)

Management and Supportive Care

In younger patients, very aggressive therapy is often undertaken for young patients with the aim of long-term cure. Induction therapy with highly toxic cytotoxic agents aiming to obtain complete remission is initially undertaken. This is followed up by post-induction remission consolidation therapy, without which relapse is inevitable within months. Consolidation therapy will often include chemotherapy and allogeneic cell transplation.

In older patients, aggressive therapy is much less likely to be tolerated and treatment needs to be taylored to take age and performacnce state into account. Remission chemotherapy is often successful in improving both life expectancy and quality of life during that time, although for patients who are more elderly or have severe comorbidities, supportive care alone is often most appropriate. A key decision in patients for whom cure cannot be achieved, is decisions regarding transfusions and other supportive care. In patients who do not have a rapidly rising peripheral blast count, life can be prolonged by

  • Regular transfusions to avoid severe anaemia
  • Platelet transfusions if a major bleed occurs
  • Broad-spectrum intravenoous antibiotics for infections

In patients with a rapidly rising blast count, hydroxyurea can be used to control the disease and prolong life, although this worsens anaemic and thrombocytopaenia.

Some patients will want very active treamtent whereas others will want a focus purely on comfort care and relief of suffering and it is usually very helpful to have conversations with the patient and family about this. Discussions will inevitably involve not only the big picture but also the practicalities of pursuing or not pursuiing treatment, such as how often transfusions might be needed and where should infections be treated.


In some patients, AML can be cured, and these patients will generally never need to be referred to a palliative care unit. The response to treatment and survival is quite variable. Some of the negative prognostic factors are:

  • Age > 60
  • Karnofsky performance score < 60
  • MDR 1-positive phenotype
  • Therapy-related AML or AML on background of myelodysplastic syndrome or a myeloproliferative or other hematologic disorder
  • Various leukaemia-specific features, including: Complex karyotypic abnormalities, -5, -7, 3q26 aberrations, t(6;9), 11q23 aberrations except for t(9;11), “monosomal karyotype”; FLT3/ITD mutation, MLL partial tandem duplication, BAALC overexpression, mutations in IDH1 and/or IDH2

Age is a key factor on the likely survival. In a large UK study of many thousands of patients, it can clearly be seen that advancing age reduces 5-year survival:[1]

Age 5 year survival
15 to 24 years 53%
25 to 39 years 49%
40 to 59 years 33%
60 to 69 years 13%
70 to 79 years 3%
Over 80 years 0%

A significant proportion of patients die during active treatment, so many patients will not end up being referred to palliative care. Older patients are more likely to be referred early, particular the very elderly, as often a decision is made for these patients at diagnosis not to pursue any active therapy.

Patients will often die of profound anaemia, a major bleed or sepsis, and so it is often difficult to predict when someone is likely to deteriorate. It is possible for patients to remain relatively stable receiving regular transfusions for a number of months and then to rapidly decline due to a serious infection. In a few patients, there will be a rapidly rising peripheral blast count that seems to double in a predictable fashion. In these patients, symptoms of leukostasis often occurs once the blast count reaches around 400 and this is a sign that death within days to a couple of weeks is likely.

Prognosis of myelodyplasia with transformation to acute leukaemia

In patients with acute transformation of myelodysplastic syndrome, the prognosis is generally very poor. A large series of patients were reviewed in a Japanese study and the median survival was 142 days. In patients over 60 disease modifying therapy, including chemotherapy and stem cell transplants, was not associated with improved survival, whereas in younger patients under the age of 60, stem cell transplantation was associated with a longer survival.[2]


  1. Shah A et al. Survival and cure of acute myeloid leukaemia in England. 1971-2006: a population-based study. Br J Haematol 2013 Aug;162(4):509-16.
  2. Okuyama N et al. Prognosis of acute myeloid leukemia transformed from myelodysplastic syndromes: a multicenter retrospective study. Leuk Res. 2013 Aug;37(8):862-7.


Graham Llewellyn Grove