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Chronic Myeloid Neoplasms

Myelodysplastic syndromes

Therapy related myelodysplastic syndrome


See also Alkylating Agents and Topoisomerase II inhibitors below

Reviewer: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 5 February 2012, last major update August 2011
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

Definition
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● May occur post-chemotherapy or post-radiation therapy
● Rarely occurs after therapy for de novo AML (Leuk Res 2008;32:1043)
● Similar genetic abnormalities as de novo myelodysplasia, AML and therapy related AML, but different frequencies (Hematology Am Soc Hematol Educ Program 2007;392)
● t(8;21) cases resemble de novo cases, but with additional dysplastic changes (Am J Clin Pathol 2002;117:306)
● Poor outcome regardless of morphologic classification, and minimal survival difference between therapy related MDS and therapy related AML (Am J Clin Pathol 2007;127:197)
● Survival varies by cytogenetic risk group (Hematology Am Soc Hematol Educ Program 2007;453)

Micro images
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Peripheral blood:

Post radiochemotherapy and splenectomy for Hodgkin’s disease, has hypogranular neutrophil with pseudo-Pelger-Huet nucleus, marked poikilocytosis of erythrocytes

Bone marrow smear:

Large erythroid precursors with lobulated nuclei and karyorrhexis

Stains:

PAS+ erythroid precursors in bone marrow smear

Molecular
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● At least 8 alternative genetic pathways
● Either Class I mutations (activating mutations of genes in tyrosine kinase-RAS/BRAF pathway, leading to increased cell proliferation), Class II mutations (inactivating mutations of genes encoding hematopoietic transcription factors, causing disturbed cell proliferation), or inactivating mutations of p53 gene (Hematology Am Soc Hematol Educ Program 2007;392)

Additional references
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Haematologica 2007;92:1389


Alkylating agents causing therapy related myelodysplastic syndrome

Definition
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● Occurs median 5 years after initiation of therapy
● Risk is associated with patient age and cumulative dose of alkylating agent
● Typically presents with myelodysplastic syndrome and bone marrow failure
● Poor prognosis; median survival is 7-8 months; may progress to AML or die without progression

Micro description
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● Peripheral blood: one or more cytopenias, anemia with macrocytosis and poikoilocytosis, dysplastic changes in neutrophils
● Bone marrow: hypercellular, normocellular or hypocellular marrow
● Often severely dysplastic changes in blood and marrow affecting two or more lineages
● Myelofibrosis (15% cases) and ringed sideroblasts common; <5% myeloblasts

Micro images
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Peripheral blood:

Post-chemotherapy for breast cancer, erythrocytes have anisopoikilocytosis with numerous macrocytes, large red cell precursor has marked nuclear lobulation

Bone marrow smear:

Numerous red cell precursors with marked nuclear lobulation, no increased myeloblasts

Molecular
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● Abnormalities of chromosomes 5 or 7 or complex cytogenetic abnormalities; also AML1 mutations (Blood 2004;104:1474)


Topoisomerase II inhibitors causing therapy related myelodysplastic syndrome

Definition
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● Occurs mean 2-3 years after initiation of topoisomerase II inhibitors such as etoposide or teniposide with doxorubicin
● Poor prognosis

Micro images
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Child 2 years post etoposide for ALL with t(9;11)(p21;q23):
   
Peripheral blood shows increased monocytes and 3% blasts


Bone marrow smear shows slight shift to immaturity with 5% blasts

Molecular
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● Balanced translocations of 11q23 and 21q22

End of Chronic Myeloid Neoplasms > Myelodysplastic syndromes > Therapy related myelodysplastic syndrome


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