Acute myeloid leukemia classification
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. ; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. , Carlos A Lopez, M.D. , Shyam Patel ; Grammar Reviewer: Natalie Harpenau, B.S.
There are three classification systems for acute myeloid leukemia. These classifications include French-American-British (FAB) , the World Health Organization (WHO), and the European LeukemiaNet (ELN) . The original classification was the French-American-British (FAB) classification, and the most recent classification was the 2017 European LeukemiaNet (ELN) classification. There are several broad classification schemes for acute promyelocytic leukemia. The most well-accepted classification scheme is risk-based classification, which categories patients into low-risk, intermediate-risk, or high-risk based on the white blood cell count and platelet count. Another classification scheme is based on the origin of the leukemia, which categorized patients as having de novo or therapy-related disease. A final classification scheme is cytogenetic-based, in which case specific chromosomal abnormalities are used to stratify patients.
Classification of Acute myeloid leukemia:
The French-American-British (FAB) classification system divided acute myeloid leukemia into 8 sub-types, 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 sub-types 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 sub-types are:
|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 hematopathologists and oncologists; however, most of the clinically significant information in the WHO schema is communicated via categorization into one of the five sub-types listed below. The 2016 revision of the WHO classification was recently developed.
The sub-types of acute myeloid leukemia are shown below:
|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.
|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 sub-types 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.
Classification of acute promyelocytic leukemia:
Acute promyelocytic leukemia is further classified in to the following several classification schemes.
Based on Risk
- Low-risk disease:
- Low-risk disease is defined as the presence of less than 10000 white blood cells per microliter and greater than 40000 platelets per microliter in the peripheral blood.
- Treatment of low-risk disease involves non-chemotherapy-based regimens, such as the combination of all trance retinoic acid and arsenic trioxide.
- Intermediate-risk disease:
- High-risk disease:
- High-risk disease is defined as the presence of greater than 10000 white blood cells per microliter in peripheral blood, regardless of the platelet count.
- Platelet count is typically less than 40,000 cells per microliter, though platelet count is not a formal criterion in the classification of acute promyelocytic leukemia.
Based on etiology
- De novo disease:
- De novo acute promyelocytic leukemia is the most common sub-type.
- This refers to development of the disease in the absence of prior cytotoxic therapy or prior precursor conditions.
- De novo acute promyelocytic leukemia is due to a sporadic events in cells, without prior DNA damaging insults. This is in contrast to therapy-related disease.
- Therapy-related disease:
- Therapy-related disease refers to the development of acute promyelocytic leukemia in-patients who were previously treated with DNA-damaging or genotoxic agents for other conditions, such as other cancers.
- The most common DNA-damaging agents that cause therapy-associated acute promyelocytic leukemia are topoisomerase inhibitors and alkylating agents.
- Therapy-related acute promyelocytic leukemia is typically seen in patients with a history of breast cancer who received cyclophosphamide or patients with a history of a germ cell tumor who have received etoposide.
- The prognosis of therapy-related disease is worse than that of de novo disease, with a 5-year survival of less than 10 years. The 4-year overall survival for therapy-related disease is 24.5%, compared to 39.5% for de novo disease.
|Topoisomerase II inhibitors:||
|Other chemotherapeutic agents:||
Based on cytogenetics
- The karyotype of most cases of acute promyelocytic leukemia involves the t(15;17) translocation between the PML and RARA genes. However, complex karyotypes may co-exist in some cases of acute promyelocytic leukemia.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Coombs CC, Tavakkoli M, Tallman MS (2015). "Acute promyelocytic leukemia: where did we start, where are we now, and the future". Blood Cancer J. 5: e304. doi:10.1038/bcj.2015.25. PMC 4450325. PMID 25885425.
- McCulloch D, Brown C, Iland H (2017). "Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives". Onco Targets Ther. 10: 1585–1601. doi:10.2147/OTT.S100513. PMC 5359123. PMID 28352191.
- Zhang YC, Zhou YQ, Yan B, Shi J, Xiu LJ, Sun YW; et al. (2015). "Secondary acute promyelocytic leukemia following chemotherapy for gastric cancer: a case report". World J Gastroenterol. 21 (14): 4402–7. doi:10.3748/wjg.v21.i14.4402. PMC 4394105. PMID 25892894.
- Zahid MF, Parnes A, Savani BN, Litzow MR, Hashmi SK (2016). "Therapy-related myeloid neoplasms - what have we learned so far?". World J Stem Cells. 8 (8): 231–42. doi:10.4252/wjsc.v8.i8.231. PMC 4999650. PMID 27621757.
- Chen C, Huang X, Wang K, Chen K, Gao D, Qian S (2018). "Early mortality in acute promyelocytic leukemia: Potential predictors". Oncol Lett. 15 (4): 4061–4069. doi:10.3892/ol.2018.7854. PMC 5835847. PMID 29541170.
- Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M (July 1993). "The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript". EMBO J. 12 (7): 2715–21. PMC 413521. PMID 8334990.