Acute promyelocytic leukemia classification: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Acute promyelocytic leukemia}} | {{Acute promyelocytic leukemia}} | ||
{{CMG}} {{shyam}} {{AE}} {{S.G.}} | {{CMG}} {{shyam}} {{AE}} {{S.G.}}; {{GRR}} {{Nat}} | ||
== Overview == | == Overview == | ||
There are several broad [[classification]] schemes for acute promyelocytic leukemia. The most well-accepted classification scheme is risk-based classification, which | 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 [[Cytogenetics|cytogenetic]]-based, in which case specific [[Chromosome abnormality|chromosomal abnormalities]] are used to stratify patients. | ||
==Classification== | ==Classification== | ||
| Line 10: | Line 10: | ||
===Based on Risk === | ===Based on Risk === | ||
*'''Low-risk disease''': | *'''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 cell|peripheral blood]]. | **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 cell|peripheral blood]].<ref name="SongPeng2017">{{cite journal|last1=Song|first1=Yu-hua|last2=Peng|first2=Peng|last3=Qiao|first3=Chun|last4=Zhang|first4=Run|last5=Li|first5=Jian-yong|last6=Lu|first6=Hua|title=Low platelet count is potentially the most important contributor to severe bleeding in patients newly diagnosed with acute promyelocytic leukemia|journal=OncoTargets and Therapy|volume=Volume 10|year=2017|pages=4917–4924|issn=1178-6930|doi=10.2147/OTT.S144438}}</ref> | ||
**Treatment of low-risk [[disease]] involves non-[[chemotherapy]]-based regimens, such as the combination of all trance [[retinoic acid]] and [[arsenic trioxide]].<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 trance [[retinoic acid]] and [[arsenic trioxide]].<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> | ||
*'''Intermediate-risk disease''': | *'''Intermediate-risk disease''': | ||
**Intermediate-risk [[disease]] is defined as the presence of less than 10000 [[white blood cells]] per | **Intermediate-risk [[disease]] is defined as the presence of less than 10000 [[white blood cells]] per microl<nowiki/>ite<nowiki/>r and less than 40000 [[Platelet|plate]]<nowiki/>[[Platelet|lets]] per microliter in [[Peripheral blood cell|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''': | ||
**High-risk [[disease]] is defined as the presence of greater than 10000 [[white blood cells]] per | **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 40000 [[Cell (biology)|cells]] per | **[[Platelet]] count is typically less than 40000 [[Cell (biology)|cells]] per microliter, though [[platelet]] count is not a formal criterion in the [[classification]] of acute promyelocytic leukemia.<ref name="pmid25885425" /> | ||
===Based on etiology=== | ===Based on etiology=== | ||
* | *'''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. | **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 [[Cell (biology)|cells]], without prior [[DNA]] damaging insults. This is in contrast to [[therapy]]-related [[disease]]. | ||
*'''Therapy-related disease''': | *'''Therapy-related disease''': | ||
**Therapy-related | **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 agent|alkylating agents]]. | **The most common [[DNA]]-damaging agents that cause therapy-associated acute promyelocytic leukemia are [[topoisomerase]] inhibitors and [[Alkylating agent|alkylating agents]]. | ||
**Therapy-related acute promyelocytic leukemia is typically seen in | **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 | **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.<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> | ||
{| class="wikitable" | {| class="wikitable" | ||
| Line 34: | Line 34: | ||
! colspan="2" |'''''Chemotherapeutic agents''''' | ! colspan="2" |'''''Chemotherapeutic agents''''' | ||
|- | |- | ||
| | |'''Topoisomerase II inhibitors:<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>''' | ||
| | | | ||
*This class of [[chemotherapeutics]] causes early-onset [[leukemia]], with a typical latency of 2-3 years from the receipt of the [[topoisomerase inhibitor]]. | *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 | *[[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. | *There is usually no preceding [[myelodysplastic]] phase; the onset of [[leukemia]] is relatively sudden. | ||
|- | |- | ||
| | |'''Alkylating agents:<ref name="pmid27621757" />''' | ||
| | | | ||
*This class of [[chemotherapeutics]] causes late-onset [[leukemia]], with a typical latency of greater than 7 years from the receipt of the [[alkylating agent]]. | *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. | *Cytogenetics from the leukemia diagnosis typically shows [[monosomy]] 5 or [[monosomy]] 7. | ||
*[[Mutation|Mutational]] analyses can show a | *[[Mutation|Mutational]] analyses can show a [[TP53]] [[mutation]]. There is usually a preceding [[myelodysplastic]] phase. | ||
|- | |- | ||
| | |'''Other [[chemotherapeutic agents]]:<ref name="pmid25892894" />''' | ||
| | | | ||
*Although other [[chemotherapy]] [[Medication|medications]] are not classically associated with therapy-related | *Although other [[chemotherapy]] [[Medication|medications]] are not classically associated with therapy-related [[Promyelocytic leukemia protein|promyelocytleukemiamiaiamia]], there have been cases of such associations. | ||
*In a [[patient]] with [[Stomach cancer|gastric cancer]] treated with [[oxaliplatin]] and [[capecitabine]], acute | *In a [[patient]] with [[Stomach cancer|gastric cancer]] treated with [[oxaliplatin]] and [[capecitabine]], acute promyleukemia leukemia developed after a latency period of 4 years. | ||
*The [[leukemic]] [[ | *The [[leukemic]] [[Cell (biology)|cells]] had [[Chromosome|chromosomal]] [[abnormalities]], suggesting that the secondary neoplasm was [[chemotherapy]]-induced rather than [[de novo]]. | ||
|} | |} | ||
===Based on cytogenetics=== | ===Based on cytogenetics=== | ||
*The | *The karyotype of most cases of acute promyelocytic leukemia involves the t(15;17) [[translocation]] between the ''[[Progressive multifocal leukoencephalopathy|PML]]'' and [[RARA gene|''RARA'' genes]]. However, complex [[Karyotype|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> | ||
{| class="wikitable" | {| class="wikitable" | ||
|+ | |+ | ||
| Line 62: | Line 62: | ||
| | | | ||
*Complex karyotype is defined as the presence of two or more [[Chromosomal abnormalities|chromosomal abnormities]]. | *Complex karyotype is defined as the presence of two or more [[Chromosomal abnormalities|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" />. | *Complex karyotype acute promyelocytic leukemia is associated with worse prognosis and lower rates of complete [[Remission (medicine)|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" /> | *Patients with complex karyotype are more likely to have a ''[[TP53]]'' [[mutation]] and are more likely to be resistant to [[chemotherapy]].<ref name="pmid29541170" /> | ||
|- | |- | ||
| Line 73: | Line 73: | ||
|'''Tetraploidy''' | |'''Tetraploidy''' | ||
| | | | ||
*[[Tetraploidy]] is defined as the presence of four sets of [[chromosomes]] in a | *[[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) [[Translocations|translocation]] between the ''PML'' and [[RARA gene|''RARA'' genes]]. | *The [[karyotype]] of most cases of acute promyelocytic leukemia involves the t(15;17) [[Translocations|translocation]] between the ''PML'' and [[RARA gene|''RARA'' genes]]. | ||
*However, complex [[Karyotype|karyotypes]] may co-exist in some cases of acute promyelocytic leukemia. | *However, complex [[Karyotype|karyotypes]] may co-exist in some cases of acute promyelocytic leukemia. | ||
* | *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]].<ref name="pmid29541170" /> | ||
|- | |- | ||
|'''t(8;21)''' | |'''t(8;21)''' | ||
| | | | ||
*The t(8;21) [[Translocations|translocation]] sometimes co-exists with the t(15;17) | *The t(8;21) [[Translocations|translocation]] sometimes co-exists with the t(15;17) translocation. | ||
*The t(8;21) | *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.<ref name="pmid8334990">{{cite journal |vauthors=Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M |title=The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript |journal=EMBO J. |volume=12 |issue=7 |pages=2715–21 |date=July 1993 |pmid=8334990 |pmc=413521 |doi= |url=}}</ref> | *A total of six cases of coexisting t(8;21) and t(15;17) have thus far been described.<ref name="pmid8334990">{{cite journal |vauthors=Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M |title=The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript |journal=EMBO J. |volume=12 |issue=7 |pages=2715–21 |date=July 1993 |pmid=8334990 |pmc=413521 |doi= |url=}}</ref> | ||
|} | |} | ||
Latest revision as of 14:45, 29 October 2019
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Acute promyelocytic leukemia Microchapters |
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Differentiating Acute promyelocytic leukemia from other Diseases |
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Diagnosis |
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Treatment |
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Case Studies |
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Acute promyelocytic leukemia classification On the Web |
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American Roentgen Ray Society Images of Acute promyelocytic leukemia classification |
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Directions to Hospitals Treating Acute promyelocytic leukemia |
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Risk calculators and risk factors for Acute promyelocytic leukemia classification |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]
Overview
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
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.[1]
- Treatment of low-risk disease involves non-chemotherapy-based regimens, such as the combination of all trance retinoic acid and arsenic trioxide.[2]
- 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.[3]
- 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 40000 cells per microliter, though platelet count is not a formal criterion in the classification of acute promyelocytic leukemia.[2]
Based on etiology
- 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:
- 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.[4]
| Chemotherapeutic agents | |
|---|---|
| Topoisomerase II inhibitors:[5] |
|
| Alkylating agents:[5] |
|
| Other chemotherapeutic agents:[4] |
|
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.[6]
| Cytogenetics | |
|---|---|
| Complex karyotype |
|
| Trisomy 8 |
|
| Tetraploidy |
|
| t(8;21) |
|
References
- ↑ Song, Yu-hua; Peng, Peng; Qiao, Chun; Zhang, Run; Li, Jian-yong; Lu, Hua (2017). "Low platelet count is potentially the most important contributor to severe bleeding in patients newly diagnosed with acute promyelocytic leukemia". OncoTargets and Therapy. Volume 10: 4917–4924. doi:10.2147/OTT.S144438. ISSN 1178-6930.
- ↑ 2.0 2.1 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.
- ↑ 4.0 4.1 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.
- ↑ 5.0 5.1 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.
- ↑ 6.0 6.1 6.2 6.3 6.4 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.
- ↑ 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.