History and exam
Key diagnostic factors
common
pallor
Common finding on physical examination due to anaemia.
ecchymoses or petechiae
Common finding on physical examination due to thrombocytopenia.
Other diagnostic factors
common
fatigue
Many patients have fatigue due to anaemia.
dizziness
Many patients have dizziness due to anaemia.
palpitations
Many patients have palpitations due to anaemia.
dyspnoea
Many patients have dyspnoea due to anaemia.
Other causes of dyspnoea include pulmonary infection (due to neutropenia) or leukaemic infiltration in the lungs.[56]
fever and infections
lymphadenopathy
Common finding on physical examination due to extramedullary leukaemic infiltration.
Enlarged lymph nodes are frequently the initial cause for seeking medical attention by the patient.
hepatosplenomegaly
Common finding on physical examination due to extramedullary leukaemic infiltration.
mucosal bleeding
Bleeding from the gums or nose may be present due to thrombocytopenia.
In female patients, heavy menstrual bleeding may be present.
uncommon
testicular mass
May be present due to extramedullary leukaemic infiltration.
skin mass (e.g., myeloid sarcoma)
May be present due to extramedullary leukaemic infiltration.[54]
skin infiltration
Leukaemia cutis may be present.[64]
The presence of cutaneous ulcers (e.g., Sweet's syndrome or pyoderma gangrenosum) may indicate underlying malignancy.
Sweet's syndrome is characterised by fever, leukocytosis (symptomatic hyperleukocytosis; symptoms include respiratory distress and altered mental status), and tender, erythematous, well-demarcated papules and plaques on skin, which show dense neutrophilic infiltrates.
Pyoderma gangrenosum is characterised by presence of ulcers on leg, or less commonly the hands. Develops as a consequence of immune dysfunction and may be associated with AML.
gingival enlargement
May be present due to extramedullary leukaemic infiltration.
bone pain
May be present due to leukemic infiltration of the bone marrow.
gastrointestinal symptoms (e.g., severe abdominal pain)
Severe abdominal pain may be present due to leukaemic infiltration or infection of the gastrointestinal tract.[57]
Acute abdomen is rarely noted on physical examination.
neurological symptoms (e.g., headache, confusion)
May be present due to meningeal leukaemic infiltration.[55]
Risk factors
strong
age over 65 years
Acute myeloid leukaemia (AML) is more common in older adults.[5][6] In the US, approximately 61% of cases are diagnosed in people aged 65 years or over (2018-2022 data).[5] The median age at diagnosis is 69 years.[5]
In the UK, approximately 66% of cases are diagnosed in people aged 65 years or over (2017 to 2018 data).[6]
previous treatment with chemotherapy
Acute myeloid leukaemia (AML) can develop in those previously treated with topoisomerase II inhibitors (e.g., etoposide, teniposide, doxorubicin) or alkylating agents (e.g., cyclophosphamide, melphalan, chlormethine), usually after a latency period of 1-5 years or 5-10 years, respectively.[11][12][13][14]
Loss of chromosome 5 and/or 7 is a common cytogenetic feature in patients treated with alkylating agents.[11][12][15]
Cytogenetic abnormalities involving chromosome 11q23 (KMT2A gene) are associated with topoisomerase II inhibitors.[11][12]
Other cytogenetic abnormalities associated with these agents include t(15;17)(q22;q12), which results in acute promyelocytic leukaemia (APL, a subtype of AML), and t(8;21).
previous haematological disorders
Risk of acute myeloid leukaemia (AML) is increased in patients with previous haematological disorders, including aplastic anaemia (particularly in the presence of monosomy 7), paroxysmal nocturnal haemoglobinuria, myelodysplastic syndrome (which evolves to AML in approximately 30% of patients), chronic myeloid leukaemia (may progress to myeloid blast crisis), chronic myelomonocytic leukaemia, and myeloproliferative neoplasms (polycythaemia vera, essential thrombocythaemia, primary myelofibrosis).[16][17][18][19][20]
inherited genetic disorders
Risk of acute myeloid leukaemia (AML) is increased in those with inherited chromosomal fragility disorders (e.g., Bloom's syndrome, Wiskott-Aldrich syndrome, ataxia telangiectasia, Kostmann's syndrome) or inherited bone marrow failure syndromes (e.g., Fanconi's anaemia, dyskeratosis congenita, Shwachman-Diamond syndrome, severe congenital neutropenia, and Diamond-Blackfan anaemia).[1][2][21][22][23][24][25][26][27]
Familial AML may be due to germline mutations of the tumour suppressor gene TP53 (Li-Fraumeni syndrome) or deletion at the C-terminal of CEBPA, which encodes a granulocytic differentiation factor.[50][51]
Neurofibromatosis due to mutations of the tumour suppressor gene NF1 at chromosome 17q11.2 predisposes to AML, usually in the second decade of life.[52]
constitutional chromosomal abnormalities
Down's syndrome (trisomy 21), Klinefelter's syndrome (XXY), and Patau's syndrome (trisomy 13) are associated with increased risk of acute myeloid leukaemia (AML).[28][29][30]
In those with Down's syndrome who develop AML, additional unbalanced chromosomal abnormalities such as dup(1q), del(6q), del(7p), dup(7q), +8, +11, and del(16q) are distinctive and may contribute to the pathogenesis.[31]
ionising radiation exposure
benzene exposure
Risk of acute myeloid leukaemia is increased in workers exposed to benzene (e.g., painters; printers, petroleum refinery workers, and chemical, rubber, and shoe manufacturing workers).[32]
Benzene exposure may also occur through smoking or gasoline vapour inhalation.[33] The risk of leukaemogenesis is proportionate to the level of exposure.[34]
Benzene exposure is associated with a depletion of CD4+ lymphocytes.[53]
weak
environmental exposures
Smoking has been found to be associated with the development of acute myeloid leukaemia (AML).[35][36]
Use of hair dyes and alcohol consumption has also been linked with AML, but the evidence is weak and inconsistent.[37][38][39][40]
A 1.1- to 1.4-fold increased risk of AML occurs in agricultural workers. This has been attributed to pesticides, diesel fuel, fertilisers, and infectious agents.[41] Abattoir workers, veterinarians, and meat packagers also have an increased risk.[42][43]
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