Acute Myeloid Leukemia (AML) Risk Factors

One study of 3363 AML registry patients reported 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 AML patients. Therapy-related AML, which can occur subsequent to radiation or chemotherapy occurred in approximately 8% of patients.

Overview of Mutagens and Oncogenic Drivers in AML1-3

aIncluded 3363 patients from Swedish Acute Leukemia Registry data collected between 1997-2006.1
bNo clinical history of prior MDS, myeloproliferative disease (MPD), or exposure to leukemogenic therapies or agents.1

In the majority of cases, patients with de novo AML have no specifically identifiable risk factors, thus the exact etiology remains unclear.4 The following provides some examples of factors that seem to be related:

The median age of diagnosis is 67.2 The incidence of AML increases with age, from ~1.3 per 100,000 population in patients <65 years old, to 12.2 cases per 100,000 population in patients >65 years.5

Sex and Ethnicity
The male to female ratio is approximately 11:9. Non-Hispanic whites have a higher incidence compared to other racial and ethnic groups.6

Prior Chemotherapy
Patients treated with chemotherapy for various malignancies have an increase in 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 uncommon, there are genetic syndromes that increase the risk of developing AML including: Down syndrome, bone marrow failure syndromes, and Li-Fraumeni syndrome.3 In addition, a familial acute leukemia syndrome has also been identified, though the prevalence remains unclear.8

Lifestyle Risk Factors

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):208-214. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed January 29, 2019. To view the most recent and complete version of the guideline, go online to The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 3. 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. 4. 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. 5. De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 2016;6(7):e441. 6. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30. 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. Nickels EM, Soodalter J, Churpek JE, Godley LA. Recognizing familiar myeloid leukemia in adults. Ther Adv Hematol. 2013;4(4):254-269.