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Leukemia - Acute

Recurrent genetic abnormalities

Therapy-related myeloid neoplasms

Reviewer: Daniela Mihova, M.D. (see Reviewers page)
Revised: 17 February 2013, last major update September 2012
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.

General
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● Included as a separate group in WHO 2008 classification
● May present as t-MDS, t-MDS/MPN or t-AML ("t-" means therapy related)
● May occur post-chemotherapy or post-radiation therapy
● Rarely occurs after therapy for de novo AML (Leuk Res 2008;32:1043)
● Includes two broad categories (see below): (1) alkylating agents or radiotherapy and (2) topoisomerase II inhibitor therapy; both cause direct DNA damage, but with different genetic and clinical features
● Note: t-MDS: has close relationship to t-AML
● t-AML has similar genetic abnormalities as de novo myelodysplasia and AML, but different frequencies (Hematology Am Soc Hematol Educ Program 2007:392)
● Survival varies by cytogenetics (Hematology Am Soc Hematol Educ Program 2007:453, Pediatr Blood Cancer 2008;50:17)
● Risk in children and adults may actually be similar (J Toxicol Environ Health B Crit Rev 2007;10:379)
● Prognosis is poor and similar in both t-MDS and t-AML, regardless of blast count (Haematologica 2007;92:1389)

Due to Alkylating agents

General
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● Alkylating agents: busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, lomustine, melphalan, mitocyn C, nitrogen mustard, procarbazine, thiotepa
● Occurs median 5 years after initiation (range, 2-11 years)
● Risk is associated with patient age and cumulative dose of alkylating agent
● Typically presents with myelodysplastic syndrome and bone marrow failure
● May progress to AML or may die without progression

Prognostic features
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● Poor prognosis (worse than de novo AML with comparable features); median survival is 7-8 months
● Survival < 1 year if abnormalities of #5, #7 or complex changes

Micro description
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● Presents as MDS, AML or MDS/MPN (CMML)
● Hypocellular marrow; severe dysplastic changes in blood and marrow in 60%
● Basophilia, myelofibrosis and ringed sideroblasts common (>15%)
● In MDS phase (50%), < 5% myeloblasts
● Primary neoplasm may persist in conjuction with therapy related myeloid neoplasm

Molecular description
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● Abnormalities of chromosomes 5 or 7 or complex cytogenetic abnormalities

Due to Topoisomerase II inhibitors

General
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● Topoisomerase II inhibitors: actimomycin, amsacrine, doxorubicin, etoposide, mitaxantrine, teniposide
● Abrupt onset <1 to 3 years after initiation of etoposide or teniposide with doxorubicin
● Presents as acute monocytic or myelomonocytic leukemia

Prognostic features
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● Poor prognosis; worse than de novo AML counterpart
● Better if have recurrent genetic abnormalities; better than t-MDS

Molecular description
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● Usually 11q23 and 21q22 abnormalities
● Also t(15;17), inv(16), t(16;16) and (9;11)

Due to other agents

General
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● Non specific immunophenotype: positive for CD7, panmyeloid markers (CD13, CD33), CD34, CD56

Case reports
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● t(4;11) related AML post-rituximab and fludarabine for SLL (Cancer Genet Cytogenet 2007;177:143)

Micro images
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Left: t-AML with t(8;21); right: t-AML with t(16;21)

End of Leukemia - Acute > Recurrent genetic abnormalities > Therapy-related myeloid neoplasms

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