Types of Acute Myeloid Leukemia (AML) and Associated Risk Factors

A study of 3363 Swedish AML registry patients found that about three-quarters of all cases of AML arose de novo, without leukemogenic exposure. Secondary AML, related to prior hematologic disorders (eg, myelodysplastic syndromes [MDS]), was reported for about 1 in 5 patients with AML. Therapy-related AML, which can occur subsequent to radiation or chemotherapy, occurred in approximately 8% of patients.1

aIncluded 3363 patients from Swedish Acute Leukemia Registry data collected between 1997-2006.
bNo clinical history of prior MDS, MPD, or exposure to leukemogenic therapies or agents.

In the majority of cases, patients with de novo AML have no specifically identifiable risk factors.3 The following provides some examples of factors that seem to be related:

Age
The median age of diagnosis is 68 years.4 As of 2018, the incidence of AML tends to increase with age, from 1.3 cases per 100,000 population in patients <50 years old, to 19.4 cases per 100,000 population in patients ≥65 years.5

Sex and Ethnicity
AML is more common in men than women.1,6 People of white race/ethnicity have a higher incidence compared to other racial and ethnic groups.4

Prior Chemotherapy
Patients treated with chemotherapy for various malignancies have an increased risk of developing acute leukemia. Risk of leukemia varies according to the underlying disease, specific agents (eg, alkylating agents, topoisomerase II inhibitors, antimetabolites), timing of exposure, and dose.2,7

Familial Risk Factors
Though fairly uncommon, there are genetic syndromes that increase the risk of developing AML including Down syndrome, bone marrow failure syndromes, and Li-Fraumeni syndrome.8 In addition, familial myeloid malignancies, including myelodysplastic syndromes (MDS) and AML, have been identified. More than 20 different genes have been implicated, but the prevalence of familial AML remains unclear.9

Lifestyle Risk Factors
Smoking.2

Environmental Risk Factors
Chemical exposure (eg, benzene) and ionizing radiation exposure.2

References: 1. Hulegårdh E, Nilsson C, Lazarevic V, et al. Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish Acute Leukemia Registry. Am J Hematol. 2015;90(3):208-14. 2. Risk Factors for Acute Myeloid Leukemia (AML). American Cancer Society website. https://www.cancer.org/cancer/acute-myeloid-leukemia/causes-risks-prevention/risk-factors.html. Updated August 21, 2018. Accessed April 22, 2021. 3. Strom SS, Oum R, Elhor Gbito KY, Garcia-Manero G, Yamamura Y. De novo acute myeloid leukemia risk factors: a Texas case-control study. Cancer. 2012;118(18):4589-4596. 4. Cancer Stat Facts: Leukemia - Acute Myeloid Leukemia (AML). National Cancer Institute website. http://seer.cancer.gov/statfacts/html/amyl.html. Accessed April 22, 2021. 5. SEER*Explorer. Acute Myeloid Leukemia, Recent Trends in SEER Age-Adjusted Incidence Rates, 2000–2018. National Cancer Institute website. https://seer.cancer.gov/explorer/application.html. Accessed April 19, 2021. 6. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71(1):7‐33. 7. Ezoe S. Secondary leukemia associated with the anti-cancer agent, etoposide, a topoisomerase II inhibitor. Int J Environ Res Public Health. 2012;9(7):2444-2453. 8. Goldin LR, Kristinsson SY, Liang XS, Derolf AR, Landgren O, Björkholm M. Familial aggregation of acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol. 2012;30(2):179-183. 9. Rio-Machin A, Vulliamy T, Hug N, et al. The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants. Nat Commun. 2020;11(1):1044.