Acute myeloid leukemia classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2] Carlos A Lopez, M.D. [3] Shyam Patel [4]

Overview

There are 3 classifications systems for acute myeloid leukemia. These include the French-American-British (FAB) classification, the World Health Organization (WHO) classification, and the European LeukemiaNet (ELN) classification. The original classification was the French-American-British (FAB) classification, and the most recent classification was the 2017 European LeukemiaNet (ELN) classification.

Classification

French-American-British classification

The French-American-British (FAB) classification system divided acute myeloid leukemia into 8 subtypes, M0 through to M7, based on the type of cell from which the leukemia developed and its degree of maturity. This was done by examining the appearance of the malignant cells under light microscopy and/or by using cytogenetics to characterize any underlying chromosomal abnormalities. The subtypes have varying prognoses and responses to therapy. Although the World Health Organization (WHO) classification (see below) may be more useful, the FAB system is still widely used as of mid-2006.

The eight FAB subtypes are:[1]

Type Name Cytogenetics
M0 Minimally differentiated AML
M1 Acute myeloblastic leukemia, without maturation
M2 Acute myeloblastic leukemia, with granulocytic maturation t(8;21)(q22;q22), t(6;9)
M3 Promyelocytic, or Acute promyelocytic leukemia (APL) t(15;17)
M4 Acute myelomonocytic leukemia inv(16)(p13q22), del(16q)
M4eo Myelomonocytic together with bone marrow eosinophilia inv(16), t(16;16)
M5 Acute monoblastic leukemia (M5a) or Acute monocytic leukemia (M5b) del (11q), t(9;11), t(11;19)
M6 Acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b)
M7 Acute megakaryoblastic leukemia t(1;22)

World Health Organization classification

The World Health Organization (WHO) classification of acute myeloid leukemia attempts to be more clinically useful and to produce more meaningful prognostic information than the FAB criteria. Each of the WHO categories contains numerous descriptive sub-categories of interest to the hematopathologist and oncologist; however, most of the clinically significant information in the WHO schema is communicated via categorization into one of the five subtypes listed below. The 2016 revision of the WHO classification was recently developed.

The subtypes of acute myeloid leukemia are shown below:[2]

Name Description ICD-O
Acute myeloid leukemia with characteristic genetic abnormalities This category includes:

Patients with acute myeloid leukemia in this category generally have a high rate of remission and a better prognosis compared to other types of acute myeloid leukemia.

Multiple
Acute myeloid leukemia with multilineage dysplasia This category includes patients who have had a prior myelodysplastic syndrome (MDS) or myeloproliferative disease (MPD) that transforms into acute myeloid leukemia. This category of acute myeloid leukemia occurs most often in elderly patients and often has a worse prognosis. Template:ICDO
Acute myeloid leukemia and MDS, therapy-related This category includes patients who have had prior chemotherapy and/or radiation and subsequently develop acute myeloid leukemia or MDS. These leukemias may be characterized by specific chromosomal abnormalities, and often carry a worse prognosis. Template:ICDO
Acute myeloid leukemia not otherwise categorized This category includes subtypes of acute myeloid leukemia that do not fall into the above categories. Template:ICDO

European LeukemiaNet classification

The European LeukemiaNet classification is a risk-based classification system that was recently revised in 2017.[6]

Name Description
Favorable risk Includes:
  • AML with translocations between chromosome 8 and chromosome 21; t(8;21); RUNX1/RUNX1T1
  • AML with inversions in chromosome 16; inv(16); CBFB/MYH11
  • AML with mutant NPM1 and wild-type FLT3
  • AML with biallelic CEBPalpha mutation
Intermediate risk Includes:
  • AML with mutant NPM1 and mutant FLT3 (FLT3-ITD)
  • AML with wild-type NPM1 and wild-type FLT3 (no FLT3-ITD)
  • AML with translocations between chromosome 9 and chromosome 21 (MLLT3-KMT2A)
  • AML with cytogenetic abnormalities not classified as favorable or adverse
Adverse risk Includes:
  • AML with translocations between chromosome 6 and chromosome 9
  • AML with inversion of chromosome 3
  • AML with translocations involving chromosome 11q23
  • AML with translocations between chromosome 6 and chromosome 9
  • AML with monosomy 5 or 7
  • AML with complex karyotype (2 or more cytogenetic abnormalities)
  • AML with mutant RUNX1, mutant ASXL1, or mutant TP53

References

  1. Bennett J, Catovsky D, Daniel M, Flandrin G, Galton D, Gralnick H, Sultan C (1976). "Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group". Br J Haematol. 33 (4): 451–8. PMID 188440.
  2. Vardiman J, Harris N, Brunning R (2002). "The World Health Organization (WHO) classification of the myeloid neoplasms". Blood. 100 (7): 2292–302. PMID 12239137. Full text.
  3. Reikvam H, Hatfield KJ, Kittang AO, Hovland R, Bruserud Ø (2011). "Acute myeloid leukemia with the t(8;21) translocation: clinical consequences and biological implications". J Biomed Biotechnol. 2011: 104631. doi:10.1155/2011/104631. PMC 3100545. PMID 21629739.
  4. Pulikkan JA, Castilla LH (2018). "Preleukemia and Leukemia-Initiating Cell Activity in inv(16) Acute Myeloid Leukemia". Front Oncol. 8: 129. doi:10.3389/fonc.2018.00129. PMC 5932169. PMID 29755956.
  5. Grimwade D, Ivey A, Huntly BJ (2016). "Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance". Blood. 127 (1): 29–41. doi:10.1182/blood-2015-07-604496. PMC 4705608. PMID 26660431.
  6. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T; et al. (2017). "Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel". Blood. 129 (4): 424–447. doi:10.1182/blood-2016-08-733196. PMC 5291965. PMID 27895058.

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