Assessment of Minimal Residual Disease in Standard-Risk AML

Ivey, Adam; Hills, Robert K.; Simpson, Michael A.; Jovanovic, Jelena V.; Gilkes, Amanda; Grech, Angela; Patel, Yashma; Bhudia, Neesa; Farah, Hassan; Mason, Joanne; Wall, Kerry; Akiki, Susanna; Griffiths, Michael; Solomon, Ellen; McCaughan, Frank; Linch, David C.; Gale, Rosemary E.; Vyas, Paresh; Freeman, Sylvie D.; Russell, Nigel; Burnett, Alan K.; Grimwade, David

Abstract

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

Citation

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., …Grimwade, D. (2016). Assessment of Minimal Residual Disease in Standard-Risk AML. New England Journal of Medicine, 374(5), 422-433. https://doi.org/10.1056/NEJMoa1507471

• Journal Article Type: Article
• Online Publication Date: Feb 4, 2016
• Publication Date: Feb 4, 2016
• Deposit Date: Jul 12, 2017
• Journal: New England Journal of Medicine
• Print ISSN: 0028-4793
• Electronic ISSN: 1533-4406
• Publisher: Massachusetts Medical Society
• Peer Reviewed: Peer Reviewed
• Volume: 374
• Issue: 5
• Pages: 422-433
• DOI: https://doi.org/10.1056/NEJMoa1507471
• Public URL: https://nottingham-repository.worktribe.com/output/1115505
• Publisher URL: https://www.nejm.org/doi/full/10.1056/NEJMoa1507471
• PMID: 26789727