The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML
Abstract
To study the characteristics and clinical impact of therapy-related acute myeloid leukemia (t-AML). 200 patients (7.0%) had t-AML and 2653 de novo AML (93%). Patients with t-AML were older (P < .0001) and they had lower white blood counts (P = .003) compared with de novo AML patients; t-AML patients had abnormal cytogenetics more frequently, with overrepresentation of 11q23 translocations as well as adverse cytogenetics, including complex and monosomal karyotypes, and with underrepresentation of intermediate-risk karyotypes (P < .0001); t-AML patients had NPM1 mutations (P < .0001) and FLT3 internal tandem duplications (P = .0005) less frequently. Younger age at diagnosis of primary malignancy and treatment with intercalating agents as well as topoisomerase II inhibitors were associated with shorter latency periods to the occurrence of t-AML. In multivariable analyses, t-AML was an adverse prognostic factor for death in complete remission but not relapse in younger intensively treated patients (P < .0001 and P = .39, respectively), relapse but not death in complete remission in older, less intensively treated patients (P = .02 and P = .22, respectively) and overall survival in younger intensively treated patients (P = .01). In more intensively treated younger adults, treatment-related toxicity had a major negative impact on outcome, possibly reflecting cumulative toxicity of cancer treatment.
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t-AML differs from de novo AML by a higher incidence of TP53 mutations, abnormalities of chromosomes 5 or 7, complex cytogenetics, and a reduced response to chemotherapy.
“There are several features that distinguish t-AML from de novo AML including a higher incidence of TP53 mutations2,3, abnormalities of chromosomes 5 or 7, complex cytogenetics, and a reduced response to chemotherapy4.”
From Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia (2015) · cites this paper as [4]
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- Authors
- Kayser, S., Döhner, K., Krauter, J., Köhne, C.-H., Horst, H. A., Held, G., von Lilienfeld-Toal, M., Wilhelm, S., Kündgen, A., Götze, K., Rummel, M., Nachbaur, D., Schlegelberger, B., Göhring, G., Späth, D., Morlok, C., Zucknick, M., Ganser, A., Döhner, H., Schlenk, R. F., & AMLSG, F. T. G.-A.
- Affiliations
- Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany;
- Universität Ulm (DE)
- Medizinische Hochschule Hannover (DE)
- Klinikum Oldenburg (DE)
- University Hospital Schleswig-Holstein (DE)
- Saarland University (DE)
- Department of Internal Medicine III, University Hospital of Bonn, Bonn, Germany;
- Städtisches Klinikum Karlsruhe (DE)
- Heinrich Heine University Düsseldorf (DE)
- Ludwig-Maximilians-Universität München (DE)
- Universitätsklinikum Gießen und Marburg (DE)
- Innsbruck Medical University (AT)
- German Cancer Research Center (DE)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-02-17
- Volume
- 117
- Issue
- 7
- Pages
- 2137-2145
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1994791499
- Cited by
- 487
- References
- 51
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 29 · 2023: 44 · 2022: 46 · 2021: 46 · 2020: 42 · 2019: 33 · 2018: 32 · 2017: 28 · 2016: 26 · 2015: 19 · 2014: 30 · 2013: 22 · 2012: 22
- FWCI
- 14.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- 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 acute myeloid leukemia, de novo acute myeloid leukemia, cytogenetics, 11q23 translocation, NPM1 mutation, FLT3-ITD, latency period, prognostic factors, relapse, overall survival, treatment toxicity, topoisomerase II inhibitors, DNA intercalators, treatment intensity
- MeSH terms
- Nucleophosmin, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Antineoplastic Agents, Chromosome Aberrations, Female, Humans, Karyotyping, Male, Middle Aged, Neoplasms, Radiation-Induced, Nuclear Proteins, Prognosis, Prospective Studies, Risk Factors, Leukemia, Myeloid, Acute, Neoplasms, Second Primary, Disease-Free Survival, fms-Like Tyrosine Kinase 3, Kaplan-Meier Estimate, Young Adult
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