The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Assessment of Minimal Residual Disease in Standard-Risk AML
Open accessAbstract
BACKGROUND: Despite the molecular heterogeneity of standard-risk acute myeloid leukemia (AML), treatment decisions are based on a limited number of molecular genetic markers and morphology-based assessment of remission. Sensitive detection of a leukemia-specific marker (e.g., a mutation in the gene encoding nucleophosmin [NPM1]) could improve prognostication by identifying submicroscopic disease during remission. METHODS: We used a reverse-transcriptase quantitative polymerase-chain-reaction assay to detect minimal residual disease in 2569 samples obtained from 346 patients with NPM1-mutated AML who had undergone intensive treatment in the National Cancer Research Institute AML17 trial. We used a custom 51-gene panel to perform targeted sequencing of 223 samples obtained at the time of diagnosis and 49 samples obtained at the time of relapse. Mutations associated with preleukemic clones were tracked by means of digital polymerase chain reaction. RESULTS: Molecular profiling highlighted the complexity of NPM1-mutated AML, with segregation of patients into more than 150 subgroups, thus precluding reliable outcome prediction. The determination of minimal-residual-disease status was more informative. Persistence of NPM1-mutated transcripts in blood was present in 15% of the patients after the second chemotherapy cycle and was associated with a greater risk of relapse after 3 years of follow-up than was an absence of such transcripts (82% vs. 30%; hazard ratio, 4.80; 95% confidence interval [CI], 2.95 to 7.80; P<0.001) and a lower rate of survival (24% vs. 75%; hazard ratio for death, 4.38; 95% CI, 2.57 to 7.47; P<0.001). The presence of minimal residual disease was the only independent prognostic factor for death in multivariate analysis (hazard ratio, 4.84; 95% CI, 2.57 to 9.15; P<0.001). These results were validated in an independent cohort. On sequential monitoring of minimal residual disease, relapse was reliably predicted by a rising level of NPM1-mutated transcripts. Although mutations associated with preleukemic clones remained detectable during ongoing remission after chemotherapy, NPM1 mutations were detected in 69 of 70 patients at the time of relapse and provided a better marker of disease status. CONCLUSIONS: The presence of minimal residual disease, as determined by quantitation of NPM1-mutated transcripts, provided powerful prognostic information independent of other risk factors. (Funded by Bloodwise and the National Institute for Health Research; Current Controlled Trials number, ISRCTN55675535.).
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Cites
Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia
The Cancer Genome Atlas Research Network (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1301689 · Cited by 5,078
Mutational landscape and significance across 12 major cancer types
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Self-citationCheson, B. D., Bennett, J. M., Kopecky, K. J., Büchner, T., Willman, C. L., Estey, E. H., Schiffer, C. A., Doehner, H., Tallman, M. S., Lister, T. A., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.036 · Cited by 2,654
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DNMT3A Mutations in Acute Myeloid Leukemia
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Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia
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Grimwade, D., Hills, R. K., Moorman, A. V., Walker, H., Chatters, S., Goldstone, A. H., Wheatley, K., Harrison, C. J., Burnett, A. K., & on behalf of the National Cancer Research Institute Adult Leukaemia Working Group (2010) · Blood · doi:10.1182/blood-2009-11-254441 · Cited by 1,938
Self-citationCytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype
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Cited by
Döhner, H., Wei, A. H., Appelbaum, F. R., Craddock, C., DiNardo, C. D., Dombret, H., Ebert, B. L., Fenaux, P., Godley, L. A., Hasserjian, R. P., et al. (2022) · Blood · doi:10.1182/blood.2022016867 · Cited by 3,279
Schuurhuis, G. J., Heuser, M., Freeman, S., Béné, M.-C., Buccisano, F., Cloos, J., Grimwade, D., Haferlach, T., Hills, R. K., Hourigan, C. S., et al. (2018) · Blood · doi:10.1182/blood-2017-09-801498 · Cited by 1,041
Self-citationMolecular Minimal Residual Disease in Acute Myeloid Leukemia
Jongen-Lavrencic, M., Grob, T., Hanekamp, D., Kavelaars, F. G., al Hinai, A., Zeilemaker, A., Erpelinck-Verschueren, C. A. J., Gradowska, P. L., Meijer, R., Cloos, J., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1716863 · Cited by 786
Short, N. J., Rytting, M. E., & Cortes, J. E. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31041-9 · Cited by 781
Pollyea, D. A., Stevens, B. M., Jones, C. L., Winters, A., Pei, S., Minhajuddin, M., D’Alessandro, A., Culp-Hill, R., Riemondy, K. A., Gillen, A. E., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0233-1 · Cited by 778
Metadata
- Authors
- Ivey, A., Hills, R. K., Simpson, M. A., Jovanovic, J. V., Gilkes, A., Grech, A., Patel, Y., Bhudia, N., Farah, H., Mason, J., Wall, K., Akiki, S., Griffiths, M., Solomon, E., McCaughan, F., Linch, D. C., Gale, R. E., Vyas, P., Freeman, S. D., Russell, N., Burnett, A. K., & Grimwade, D.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2016-02-04
- Volume
- 374
- Issue
- 5
- Pages
- 422-433
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2276580523
- Cited by
- 845
- References
- 37
- FWCI
- 88.22
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ivey, A., Hills, R. K., Simpson, M. A., Jovanovic, J. V., Gilkes, A., Grech, A., Patel, Y., Bhudia, N., Farah, H., Mason, J., Wall, K., Akiki, S., Griffiths, M., Solomon, E., McCaughan, F., Linch, D. C., Gale, R. E., Vyas, P., Freeman, S. D., . . . Grimwade, D. (2016). Assessment of Minimal Residual Disease in Standard-Risk AML. New England Journal of Medicine. https://doi.org/10.1056/nejmoa1507471
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