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Diagnosing AML

Causes of AML

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De novo AML

Patients are known as having de novo AML if they were initially diagnosed with AML without any clinical history of1:

Exposure to cancer-causing therapies

Although research has examined the epidemiology of AML, its etiology is not well understood. Evidence does show that AML occurs at a higher rate in males.2-4

Mangifying glass with DNA icon

Secondary AML

Secondary AML (sAML) is defined as AML with antecedent hematological disease (AHD).5 sAML accounts for approximately 25% of all AML cases and is associated with poor outcomes.

sAML arises as a result of6:
A prior myeloid malignancy
Newly diagnosed AML that presents with marked dysplasia
AML that emerges after prior cytotoxic chemotherapy or radiation

AML risk factors

There are well-established risk factors for AML, which include7:

Icon Elderly man
Advanced age
Icon Male
Male sex
Icon Prior treatment for cancer
Prior treatment for cancer
Icon Prior myeloid malignancies Prior myeloid malignancies
Icon Smoking exposure Smoking exposurea

While some individuals diagnosed with AML may have known risk factors, others may not.7

aThere is ongoing research and evidence pointing to the deleterious effects of smoking and its relation to AML.8,9

Signs and symptoms of AML

As the signs and symptoms of AML can resemble many other diseases, several tests may be necessary to accurately diagnose AML.10,11 Patients should be referred to a specialist at the first sign or symptom of a blood disorder or malignancy.

Signs and symptoms can include11-13:

Icon Pale complexion
Pale complexion

Due to anemia

Icon Fever

Due to neutropenia

Icon Unexplained weight loss
Unexplained weight loss

A nonspecific symptom of AML

Icon Dyspnea

Due to anemia

Icon Headache

Due to anemia

Icon Bleeding

Due to low platelet count

Icon Splenomegaly

Due to an aggregation of leukemic cells in the spleen

Icon Hepatomegaly

Due to an aggregation of leukemic cells in the liver

Diagnostic tests for AML

Testing methodologies require adequate samples of marrow and peripheral blood at diagnosis.10

These are used to build a more complete analysis and get a better picture of the genetic status of the patient’s AML.14,15

Blood count testing

Complete blood cell counts and differential14

Evaluation of bone marrow function and assessment of hematopoiesis14


Blast cell enumeration and lineage assignment, and overview of hematopoiesis14

Molecular genetics

Diagnostic testing and risk assessment of gene mutations14

Biomarker testing may confirm a diagnosis or mark a specific genetic mutation14,16


Karyotyping chromosomal translocations, inversions, and deletions14

Diagnosis and assessment of risk due to translocations, deletions, and normal or complex karyotypes14

Multiparameter flow cytometry

Useful in rapidly determining the blast lineage and antigenic profiles to provide a narrow differential or definitive diagnosis of AML17

Comprehensive molecular profiling, including IDH1, IDH2, FLT3, NPM1, CEBPA, and KIT, is important in determining prognostication and risk assessment in certain AML patient types. Rapid PCR tests by platforms such as NeoGenomics can provide test results in under 4 days, which may help identify actionable targets.18,19

Evolving classification systems of AML: FAB, WHO, and ICC

Diagnosing patients with AML is a challenge, and correctly diagnosing AML is of paramount importance to properly plan treatment strategies.14

Different classification systems of AML have been established. These are based on etiology, morphology, immunophenotype, and genetics.10,20

The French-American-British (FAB) system uses morphology and cytochemical criteria10,20
The World Health Organization (WHO), which has largely replaced the FAB system, adds genetic abnormalities to further define AML10,20
The International Consensus Classification (ICC) of Myeloid Neoplasms and Acute Leukemias recognizes the MDS to AML continuum
The new MDS/AML classification is defined as a cytopenic myeloid neoplasm and 10% to 19% blasts in the blood or bone marrow21
The 5th edition of the WHO classification of hematolymphoid tumors retains the 20% blast cutoff to define AMLb; however, patients who classify as MDS-IB2 may be regarded as AML-equivalent for therapeutic considerations.22

bThe blast count cutoff is eliminated entirely for AML with defining genetic alterations.22

Review treatment considerations for your AML patients
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AML, acute myeloid leukemia; MDS, myelodysplastic syndromes; MDS-IB2, MDS with increased blasts 2; MPN, myeloproliferative neoplasm; PCR, polymerase chain reaction.

References: 1. Abuhelwa Z, Al Shaer Q, Taha S, Ayoub K, Amer R. Characteristics of de novo acute myeloid leukemia patients in Palestine: experience of An-Najah National University Hospital. Asian Pac J Cancer Prev. 2017;18(9):2459-2464. doi:10.22034/APJCP.2017.18.9.2459 2. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33. doi:10.3322/caac.21654 [Erratum in CA Cancer J Clin. 2021;71(4):359] 3. Lindsley RC, Mar BG, Mazzola E, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood. 2015;125(9):1367-1376. doi:10.1182/blood-2014-11-610543 4. Tebbi CK. Etiology of acute leukemia: a review. Cancers (Basel). 2021;13(9):2256. doi:10.3390/cancers13092256 5. Granfeldt Østgård LS, Medeiros BC, Sengeløv H, et al. Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a national population-based cohort study. J Clin Oncol. 2015;33(31):3641-3649. doi:10.1200/JCO.2014.60.0890 6. Kuykendall A, Duployez N, Boissel N, Lancet JE, Welch JS. Acute myeloid leukemia: the good, the bad, and the ugly. Am Soc Clin Oncol Educ Book. 2018;38:555-573. doi:10.1200/EDBK_199519 7. Acute myelogenous leukemia: symptoms and causes. Mayo Clinic. Accessed July 19, 2023. %20Acute%20myelogenous%20leukemia 8. Kristensen D, Nielsen LB, Roug AS, et al. The prognostic effect of smoking status on intensively treated acute myeloid leukaemia—a Danish nationwide cohort study. Br J Haematol. 2020;190(2):236-243. doi:10.1111/bjh.16667 9. Wang P, Liu H, Jiang T, Yang J. Cigarette smoking and the risk of adult myeloid disease: a meta-analysis. PLoS One. 2015;10(9):e0137300. doi:10.1371/journal.pone.0137300 10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.4.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 10, 2023. To view the most recent and complete version of the guideline, go online to 11. Acute myeloid leukemia: signs and symptoms. Leukemia & Lymphoma Society. Accessed July 19, 2023. 12. Signs and symptoms of acute myeloid leukemia (AML). American Cancer Society. Accessed July 19, 2023. 13. Murakami J, Shimizu Y. Hepatic manifestations in hematological disorders. Int J Hepatol. 2013;2013:484903. doi:10.1155/2013/484903 14. Roug AS, Hansen MC, Nederby L, Hokland P. Diagnosing and following adult patients with acute myeloid leukaemia in the genomic age. Br J Haematol. 2014;167(2):162-176. doi:10.1111/bjh.13048 [Erratum in Br J Haematol. 2015;168(6):920] 15. Leukemia - acute myeloid – AML: diagnosis. Cancer.Net. Approved April 2022. Accessed July 19, 2023. 16. Sokolenko AP, Imyanitov EN. Molecular diagnostics in clinical oncology. Front Mol Biosci. 2018;5:76. doi:10.3389/fmolb.2018.00076 17. Peters JM, Ansari MQ. Multiparameter flow cytometry in the diagnosis and management of acute leukemia. Arch Pathol Lab Med. 2011;135(1):44-54. doi:10.5858/2010-0387-RAR. 18. Leisch M, Jansko B, Zaborsky N, Greil R, Pleyer L. Next generation sequencing in AML—on the way to becoming a new standard for treatment initiation and/or modulation? Cancers (Basel). 2019;11(2):252. doi:10.3390/cancers11020252 19. Data on file. Servier Pharmaceuticals LLC. 20. Arber DA, Borowitz MJ, Cessna M, et al. Initial diagnostic workup of acute leukemia: guideline from the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017;141(10):1342-1393. doi:10.5858/arpa.2016-0504-CP 21. Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140(11):1200-1228. doi:10.1182/blood.2022015850 22. Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36(7):1703-1719. doi:10.1038/s41375-022-01613-1