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==Overview== | ==Overview== | ||
There are 3 classification systems for acute myeloid leukemia. These include the [[French-American-British classification | 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 classification | French-American-British (FAB) classification]], and the most recent classification was the 2017 | There are 3 classification systems for acute myeloid leukemia. These include the [[French-American-British classification | 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 classification | 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 classification|acute promyelocytic leukemia]]. The most well-accepted [[Acute promyelocytic leukemia classification|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 == | == Classification of Acute myeloid leukemia: == | ||
===French-American-British classification=== | ===French-American-British classification=== | ||
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==Classification of acute promyelocytic leukemia:== | |||
[[Acute promyelocytic leukemia classification|Acute promyelocytic leukemi]]<nowiki/>a is further classified in to the following several classification schemes. | |||
===Risk classification=== | |||
*'''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.<ref name="pmid25885425">{{cite journal| author=Coombs CC, Tavakkoli M, Tallman MS| title=Acute promyelocytic leukemia: where did we start, where are we now, and the future. | journal=Blood Cancer J | year= 2015 | volume= 5 | issue= | pages= e304 | pmid=25885425 | doi=10.1038/bcj.2015.25 | pmc=4450325 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25885425 }}</ref> Treatment of low-risk disease involves non-chemotherapy-based regimens, such as the combination of [[all-''trans'' retinoic acid]] and [[arsenic trioxide]].<ref name="pmid25885425" /> | |||
*'''Intermediate-risk disease''': Intermediate-risk disease is defined as the presence of less than 10000 [[white blood cells]] per microliter and less than 40000 platelets per microliter in peripheral blood.<ref name="pmid28352191">{{cite journal| author=McCulloch D, Brown C, Iland H| title=Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives. | journal=Onco Targets Ther | year= 2017 | volume= 10 | issue= | pages= 1585-1601 | pmid=28352191 | doi=10.2147/OTT.S100513 | pmc=5359123 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28352191 }}</ref> | |||
*'''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.<ref name="pmid25885425" /> [[Platelet]] count is typically less than 40000 cells per microliter, though [[platelet]] count is not a formal criterion in the classification of acute promyelocytic leukemia. | |||
===Origin-based classification=== | |||
*'''''De novo'' disease''': ''De novo'' acute promyelocytic leukemia is the most common subtype. 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'''<ref name="pmid21039422">{{cite journal| author=Sill H, Olipitz W, Zebisch A, Schulz E, Wölfler A| title=Therapy-related myeloid neoplasms: pathobiology and clinical characteristics. | journal=Br J Pharmacol | year= 2011 | volume= 162 | issue= 4 | pages= 792-805 | pmid=21039422 | doi=10.1111/j.1476-5381.2010.01100.x | pmc=3042191 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21039422 }}</ref>: 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.<ref name="pmid21039422" /> 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.<ref name="pmid25892894">{{cite journal| author=Zhang YC, Zhou YQ, Yan B, Shi J, Xiu LJ, Sun YW et al.| title=Secondary acute promyelocytic leukemia following chemotherapy for gastric cancer: a case report. | journal=World J Gastroenterol | year= 2015 | volume= 21 | issue= 14 | pages= 4402-7 | pmid=25892894 | doi=10.3748/wjg.v21.i14.4402 | pmc=4394105 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25892894 }}</ref> The 4-year overall survival for therapy-related disease is 24.5%, compared to 39.5% for ''de novo'' disease. | |||
**''Topoisomerase II inhibitors'': This class of chemotherapeutics causes early-onset leukemia, with a typical latency of 2-3 years from the receipt of the topoisomerase inhibitor. Cytogenetics from the leukemia diagnosis typically shows the ''MLL'' rearrangement (chromosome 11q23). There is usually no preceding myelodysplastic phase; the onset of leukemia is relatively sudden.<ref name="pmid27621757">{{cite journal| author=Zahid MF, Parnes A, Savani BN, Litzow MR, Hashmi SK| title=Therapy-related myeloid neoplasms - what have we learned so far? | journal=World J Stem Cells | year= 2016 | volume= 8 | issue= 8 | pages= 231-42 | pmid=27621757 | doi=10.4252/wjsc.v8.i8.231 | pmc=4999650 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27621757 }}</ref> | |||
**''Alkylating agents'': This class of chemotherapeutics causes late-onset leukemia, with a typical latency of greater than 7 years from the receipt of the alkylating agent. Cytogenetics from the leukemia diagnosis typically shows monosomy 5 or monosomy 7. Mutational analyses can show a ''TP53'' mutation. There is usually a preceding myelodysplastic phase.<ref name="pmid27621757" /> | |||
**''Other chemotherapeutic agents'': Although other chemotherapy medications are not classically associated with therapy-related acute promyelocytic leukemia, there have been cases of such associations. In a patient with gastric cancer treated with oxaliplatin and capecitabine, acute promyelocytic leukemia developed after a latency period of 4 years.<ref name="pmid25892894" /> The leukemic cells had chromosomal abnormalities, suggesting that the secondary neoplasm was chemotherapy-induced rather than ''de novo''. | |||
===Cytogenetic-based classification=== | |||
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.<ref name="pmid29541170">{{cite journal| author=Chen C, Huang X, Wang K, Chen K, Gao D, Qian S| title=Early mortality in acute promyelocytic leukemia: Potential predictors. | journal=Oncol Lett | year= 2018 | volume= 15 | issue= 4 | pages= 4061-4069 | pmid=29541170 | doi=10.3892/ol.2018.7854 | pmc=5835847 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29541170 }}</ref> | |||
*'''Complex karyotype''': Complex karyotype is defined as the presence of two or more chromosomal abnormities. Complex karyotype acute promyelocytic leukemia is associated with worse prognosis and lower rates of complete remission, similar to complex karyotype [[acute myeloid leukemia]]<ref name="pmid29541170" />. Patients with complex karyotype are more likely to have a ''TP53'' mutation and are more likely to be resistant to chemotherapy.<ref name="pmid29541170" /> | |||
*'''Trisomy 8''': Trisomy 8 is characterized by three copies of chromosome 8 in cells. This chromosomal abnormality is commonly found in patients with [[myelodysplastic syndrome]], which is a precursor condition for [[acute myeloid leukemia]].<ref name="pmid29541170" /> Aside from t(15;17), trisomy 8 is the most frequent chromosomal abnormality in acute promyelocytic leukemia. | |||
*'''Tetraploidy''': Tetraploidy is defined as the presence of four sets of chromosomes in a cell. Tetraploidy is generally rare in acute promyelocytic leukemia and accounts for approximately 0.75% of cases. 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.<ref name="pmid29541170" /> Tetraploidy in acute promyelocytic leukemia is more commonly associated with CD2 expression in the malignant cells. Tetraploid acute promyelocytic leukemia is mostly sensitive to all-''trans'' retinoic acid. | |||
*'''t(8;21)''': The t(8;21) translocation sometimes co-exists with the t(15;17) translocation. The t(8;21) translocation is more commonly found in [[acute myeloid leukemia]] and involves the juxtaposition of the ''ETO'' (''RUNX1T1'') gene on chromosome 8 with ''AML1'' (''RUNX1'') gene on chromosome 21. A total of six cases of coexisting t(8;21) and t(15;17) have thus far been described. | |||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
Revision as of 17:02, 6 January 2019
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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 classification 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. 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:
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:
|
| Intermediate risk | Includes:
|
| Adverse risk | Includes:
|
Classification of acute promyelocytic leukemia:
Acute promyelocytic leukemia is further classified in to the following several classification schemes.
Risk classification
- 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.[7] Treatment of low-risk disease involves non-chemotherapy-based regimens, such as the combination of all-''trans'' retinoic acid and arsenic trioxide.[7]
- Intermediate-risk disease: Intermediate-risk disease is defined as the presence of less than 10000 white blood cells per microliter and less than 40000 platelets per microliter in peripheral blood.[8]
- 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.[7] Platelet count is typically less than 40000 cells per microliter, though platelet count is not a formal criterion in the classification of acute promyelocytic leukemia.
Origin-based classification
- De novo disease: De novo acute promyelocytic leukemia is the most common subtype. 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[9]: 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.[9] 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.[10] The 4-year overall survival for therapy-related disease is 24.5%, compared to 39.5% for de novo disease.
- Topoisomerase II inhibitors: This class of chemotherapeutics causes early-onset leukemia, with a typical latency of 2-3 years from the receipt of the topoisomerase inhibitor. Cytogenetics from the leukemia diagnosis typically shows the MLL rearrangement (chromosome 11q23). There is usually no preceding myelodysplastic phase; the onset of leukemia is relatively sudden.[11]
- Alkylating agents: This class of chemotherapeutics causes late-onset leukemia, with a typical latency of greater than 7 years from the receipt of the alkylating agent. Cytogenetics from the leukemia diagnosis typically shows monosomy 5 or monosomy 7. Mutational analyses can show a TP53 mutation. There is usually a preceding myelodysplastic phase.[11]
- Other chemotherapeutic agents: Although other chemotherapy medications are not classically associated with therapy-related acute promyelocytic leukemia, there have been cases of such associations. In a patient with gastric cancer treated with oxaliplatin and capecitabine, acute promyelocytic leukemia developed after a latency period of 4 years.[10] The leukemic cells had chromosomal abnormalities, suggesting that the secondary neoplasm was chemotherapy-induced rather than de novo.
Cytogenetic-based classification
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.[12]
- Complex karyotype: Complex karyotype is defined as the presence of two or more chromosomal abnormities. Complex karyotype acute promyelocytic leukemia is associated with worse prognosis and lower rates of complete remission, similar to complex karyotype acute myeloid leukemia[12]. Patients with complex karyotype are more likely to have a TP53 mutation and are more likely to be resistant to chemotherapy.[12]
- Trisomy 8: Trisomy 8 is characterized by three copies of chromosome 8 in cells. This chromosomal abnormality is commonly found in patients with myelodysplastic syndrome, which is a precursor condition for acute myeloid leukemia.[12] Aside from t(15;17), trisomy 8 is the most frequent chromosomal abnormality in acute promyelocytic leukemia.
- Tetraploidy: Tetraploidy is defined as the presence of four sets of chromosomes in a cell. Tetraploidy is generally rare in acute promyelocytic leukemia and accounts for approximately 0.75% of cases. 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.[12] Tetraploidy in acute promyelocytic leukemia is more commonly associated with CD2 expression in the malignant cells. Tetraploid acute promyelocytic leukemia is mostly sensitive to all-trans retinoic acid.
- t(8;21): The t(8;21) translocation sometimes co-exists with the t(15;17) translocation. The t(8;21) translocation is more commonly found in acute myeloid leukemia and involves the juxtaposition of the ETO (RUNX1T1) gene on chromosome 8 with AML1 (RUNX1) gene on chromosome 21. A total of six cases of coexisting t(8;21) and t(15;17) have thus far been described.
References
- ↑ 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.
- ↑ 7.0 7.1 7.2 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.
- ↑ 9.0 9.1 Sill H, Olipitz W, Zebisch A, Schulz E, Wölfler A (2011). "Therapy-related myeloid neoplasms: pathobiology and clinical characteristics". Br J Pharmacol. 162 (4): 792–805. doi:10.1111/j.1476-5381.2010.01100.x. PMC 3042191. PMID 21039422.
- ↑ 10.0 10.1 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.
- ↑ 11.0 11.1 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.
- ↑ 12.0 12.1 12.2 12.3 12.4 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.