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Therapy-related leukemia and myelodysplasia: susceptibility and incidence
Open accessAbstract
Therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) is an increasingly recognized treatment complication in patients treated with radiotherapy or chemotherapy for previous hematologic malignancies or solid tumors. Distinct clinical entities have been described according to the primary treatment, corresponding to defined genetic lesions. Chromosome 7 and/or 5 losses or deletions are typical of alkylating agent-induced AML, while development of t-AML with balanced translocations involving chromosome bands 11q23 and 21q22 has been related to previous therapy with drugs targeting DNA-topoisomerase II. In addition, antimetabolites, and in particular the immunosuppressant azathioprine, have been shown to induce defective DNA-mismatch repair. This could promote survival of misrepaired cells giving rise to the leukemic clone. Individual predisposing factors, including polymorphisms in detoxification and DNA repair enzymes have been identified. Their combination may significantly increase the risk of t-MDS/AML. Among patients with hematologic malignancies, long-term survivors of Hodgkin's lymphoma are exposed to an increased risk of t-MDS/AML, particularly when receiving MOPP-based, and escalated BEACOPP regimens, and when alkylators are combined with radiotherapy. Patients with Hodgkin's and non-Hodgkin's lymphoma are at highest risk when total body irradiation followed by autologous stem cell transplantation is used as rescue or consolidation therapy. The addition of granulocyte-colony-stimulating factor and radiotherapy plays a significant role in t-AML following treatment of children with acute lymphoblastic leukemia. In non-hematologic malignancies, treatment for breast cancer and germ-cell tumors has been associated with a 1-5% lifetime risk of both lymphoid as well as myeloid leukemia. In all cases the risk of t-MDS/AML drops sharply by 10 years after treatment.
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“Secondary cancers are frequently acute myeloid leukaemias 155 , which may be caused by previous exposure to DNA-damaging alkylators, often arising after a median of around 7 years after initial treatment 158 .”
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Metadata
- Authors
- Leone, G., Pagano, L., Ben-Yehuda, D., & Voso, M. T.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- Corresponding author
- Leone, G.
- Venue
- Haematologica
- Published
- 2007-10-01
- Volume
- 92
- Issue
- 10
- Pages
- 1389-1398
- ISSN
- 0390-6078 (ISSN-L)
- 1592-8721
- OpenAlex
- W2148305047
- Cited by
- 236
- References
- 73
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 4 · 2023: 9 · 2022: 16 · 2021: 15 · 2020: 2 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 12 · 2015: 16 · 2014: 15 · 2013: 15 · 2012: 19
- FWCI
- 10.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Haematologica (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- therapy-related myelodysplastic syndrome, therapy-related acute myeloid leukemia, secondary malignancies, alkylating agents, topoisomerase II inhibitors, azathioprine, DNA mismatch repair, 11q23 translocation, Hodgkin's disease, non-Hodgkin lymphoma, total body irradiation, autologous stem cell transplantation, granulocyte colony-stimulating factor, acute lymphoblastic leukemia, breast cancer, germ cell tumors, genetic susceptibility, polymorphism
- MeSH terms
- Animals, Disease Susceptibility, DNA, DNA Topoisomerases, Type II, DNA Repair, Humans, Leukemia, Myelodysplastic Syndromes, Polymorphism, Genetic, Radiotherapy, Risk Factors, Incidence, Topoisomerase II Inhibitors, Drug-Related Side Effects and Adverse Reactions
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