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Leukemia, Acute Myeloid

Leukemia, Acute Myeloid is a topic covered in the 5-Minute Clinical Consult.

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Basics

Description

  • Acute myeloid leukemia (AML) is characterized by proliferation and accumulation of abnormal immature myeloid progenitors (blasts) with reduced capacity to differentiate into more mature cellular elements. This leads to bone marrow failure and results in a variety of systemic symptoms.
  • Previously, the French–American–British (FAB) classification system divided AML based on the cell morphology with the addition of cytogenetics (subtypes M0 to M7).
  • The World Health Organization (WHO) classification attempts to provide more meaningful prognostic information.
    • AML with characteristic genetic abnormalities: translocation t(8;21), t(15;17), and inversion in chromosome 16 inv(16)
    • AML with multilineage dysplasia: presence of a prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) that transformed into AML
    • AML and MDS, therapy related
    • AML not otherwise categorized
    • Acute leukemias of ambiguous lineage (biphenotypic acute leukemia)

Epidemiology

  • ~19,950 cases estimated in 2016 making it the most common type of leukemia in adults
  • Predominant sex: male ≥ female

Incidence
The incidence of AML increases with age, and median age is 67 years.

Etiology and Pathophysiology

Precise causes unknown, but some risk factors have been identified (see “Risk Factors”)

Genetics
  • Unknown; some are familial.
  • Cytogenetics and genetics play an important role in diagnosis and prognosis of AML and have implications for therapy.
  • Three risk groups
    • Good risk: inv(16), t(8;21), t(15;17)
    • Standard risk: normal karyotype
    • Poor risk: monosomy 5 and 7 (typically secondary AML), deletion 5q, abnormalities of 11q23 or complex karyotype
  • FLT3 gene mutations, especially internal tandem duplications (FLT3-ITD), have been associated with poor survival in AML. These and growing list of (onco)gene (e.g., NPM1, DNMT3A, and P53) mutations have been studied to further risk-stratify patients (1,2)[A].

Risk Factors

  • Genetic predisposition (e.g., Down syndrome); other familial disorders are Bloom syndrome (~25% develop AML), Fanconi anemia (52%), neurofibromatosis, Li-Fraumeni syndrome, Wiskott-Aldrich syndrome, Kostmann syndrome, and Diamond-Blackfan anemia.
  • Radiation exposure
  • Immunodeficiency states
  • Chemical and drug exposure (nitrogen mustard and alkylating agents; benzene)
  • MDS
  • Cigarette smoking

General Prevention

None currently identified, but treatment of high-risk MDS with demethylating agents (5-azacitidine [Vidaza]) has been shown to prolong time to transformation from MDS into AML (3)[A]

Commonly Associated Conditions

The following are oncologic emergencies:

  • Disseminated intravascular coagulopathy (DIC) especially in acute promyelocytic leukemia (APL) but may be seen in any AML
  • Leukostasis (high blast number and increased adhesive ability of blasts)
  • Tumor lysis syndrome (TLS): spontaneous or in response to chemotherapy

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Citation

Stephens, Mark B., et al., editors. "Leukemia, Acute Myeloid." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117516/all/Leukemia_Acute_Myeloid.
Leukemia, Acute Myeloid. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117516/all/Leukemia_Acute_Myeloid. Accessed August 21, 2019.
Leukemia, Acute Myeloid. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117516/all/Leukemia_Acute_Myeloid
Leukemia, Acute Myeloid [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 August 21]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117516/all/Leukemia_Acute_Myeloid.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Leukemia, Acute Myeloid ID - 117516 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117516/all/Leukemia_Acute_Myeloid PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -