HAEM5:Myeloid neoplasm post cytotoxic therapy: Difference between revisions

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{{DISPLAYTITLE:Myeloid neoplasm post cytotoxic therapy}}
{{DISPLAYTITLE:Myeloid neoplasm post cytotoxic therapy}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


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<blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Therapy-Related Myeloid Neoplasms]].
<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Therapy-Related Myeloid Neoplasms]].


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==Definition / Description of Disease==
-Therapy related disease that occurs as a complication of cytotoxic chemotherapy and/or radiation therapy administered for a prior neoplastic or non-neoplastic disorder.
-Excluded from this category are progression of MPN and primary MDS or MDS/MPN to AML as progression to AML is part of the natural history of the primary disease and is nearly impossible to distinguish.
==Synonyms / Terminology==
-Therapy related acute myeloid leukemia
-Alkylating agent related
-Epipodophyllotoxin related
-Therapy related acute myeloid leukemia, NOS
==Epidemiology / Prevalence==
-Therapy related myeloid neoplasms (tMN) account for 10-20% of all cases of AML, MDS, and MDS/MPN. The incidence of tMN amongst treated patients depends on the underlying disease and the treatment strategy (see table below).
-Data suggest that about 70% of patients have been treated previously for a solid tumor and 30% have been treated for a hematological neoplasm. Breast cancer and non-Hodgkin lymphoma account for the largest number of cases, respectively.
-Between 5-20% of cases occur following therapy for a non-neoplastic disorder.
-All age groups affected, but risk rises with age.
==Clinical Features==
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{| class="wikitable"
|'''Signs and Symptoms'''
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
<span class="blue-text">EXAMPLE:</span> Fatigue
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|<span class="blue-text">EXAMPLE:</span> Cytopenias
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
|}
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Two subsets of tMNs are generally recognized clinically:
More common, occurs 5-10 years after exposure to alkylating agents and/or ionizing radiation. Often present with an MDS with bone marrow failure and one or more cytopenias. Rare subset may present with tMDS/MPN or tAML.
#Commonly associated with unbalanced loss of gtenetic material, often involving chromosomes 5 and/or 7, as well as complex karyotypes and mutations or loss of TP53.
#Accounts for 20-30% of cases and has a shorter latent period of about 1-5 years. Usually follows treatment with DNA topoisomerase II. Most cases present with overt AML and often associated with a balanced chromosomal translocation.
Sites of Involvement
Bone marrow and blood. Initial presentation as extramedullary myeloid sarcoma has been reported.
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==Sites of Involvement==
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==Morphologic Features==
-Most patients present with MDS or acute leukemia associated with multi-lineage dysplasia.
-Peripheral blood shows one or more cytopenias.
-Anemia is almost always present and RBC morphology is usually macrocytic and poikilocytic.
-neutrophils show abnormal nuclear segmentation and hypogranulation.
-basophilia is often present.
-Bone marrow may be hypo/hyper/or normocellular. Reticulin fibrosis is common.
-Dysgranulopoiesis and dyserythropoiesis is common.
-Dysplastic megakaryocytes with non lobated or hypolobated neuclie or widely separated lobes are common.
==Immunophenotype==
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|-
!Finding!!Marker
|-
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
|-
|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
|-
|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
|-
|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
|}
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-Immunophenotypic findings reflect the heterogeneity of the underlying morphology.
-Blasts are generally CD34+ and express pan-myeloid antigens: CD13, CD 33, and MPO (MPO may be downregulated).
Additional Description:
-p53 positive cells in bone marrow biopsies have been demonstrated to correlate well with TP53 mutations and with a poor prognosis.
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==WHO Essential and Desirable Genetic Diagnostic Criteria==
==WHO Essential and Desirable Genetic Diagnostic Criteria==
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* Chromosomal Rearrangements (Gene Fusions)
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Individual Region Genomic Gain/Loss/LOH
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-Leukemic cells of >90% of patients with tMN show an abnormal karyotype.
-Leukemic cells of >90% of patients with tMN show an abnormal karyotype.
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|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.


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Thought to be the consequence of mutation events in hematopoietic stem cells induced by cytotoxic therapy or selection of a myeloid clone with a mutator phenotype. Only a small proportion of patients treated with identical protocols develop tMN, suggesting that some individuals may have predisopistion due to mutations in DNA damage sensing or prepair genes, or polymorphisms in genes that affect drug metabolism, transport, or repair.
Thought to be the consequence of mutation events in hematopoietic stem cells induced by cytotoxic therapy or selection of a myeloid clone with a mutator phenotype. Only a small proportion of patients treated with identical protocols develop tMN, suggesting that some individuals may have predisopistion due to mutations in DNA damage sensing or prepair genes, or polymorphisms in genes that affect drug metabolism, transport, or repair.
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'''
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==Notes==
==Notes==
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<nowiki>*</nowiki>''Citation of this Page'': “Myeloid neoplasm post cytotoxic therapy”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myeloid_neoplasm_post_cytotoxic_therapy</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Myeloid neoplasm post cytotoxic therapy”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myeloid_neoplasm_post_cytotoxic_therapy</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases M]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases M]]