Pre-emptive detection and evolution of relapse in acute myeloid leukemia by flow cytometric measurable residual disease surveillance.

Autor: McCarthy N; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK., Gui G; Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Dumezy F; Laboratory of Hematology, Lille University Hospital, Lille, France., Roumier C; Laboratory of Hematology, Lille University Hospital, Lille, France., Andrew G; Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Green S; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK., Jenkins M; Imperial College, London, UK., Adams A; University of Edinburgh, Edinburgh, UK., Khan N; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK., Craddock C; Clinical Trials Unit, University of Warwick, Coventry, UK., Hourigan CS; Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Plesa A; Lyon University Hospital, CHU-HCL, Lyon Sud, Pierre Benite, France., Freeman S; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. s.freeman@bham.ac.uk.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2024 Aug; Vol. 38 (8), pp. 1667-1673. Date of Electronic Publication: 2024 Jun 18.
DOI: 10.1038/s41375-024-02300-z
Abstrakt: Measurable residual disease (MRD) surveillance in acute myeloid leukemia (AML) may identify patients destined for relapse and thus provide the option of pre-emptive therapy to improve their outcome. Whilst flow cytometric MRD (Flow-MRD) can be applied to high-risk AML/ myelodysplasia patients, its diagnostic performance for detecting impending relapse is unknown. We evaluated this in a cohort comprising 136 true positives (bone marrows preceding relapse by a median of 2.45 months) and 155 true negatives (bone marrows during sustained remission). At an optimal Flow-MRD threshold of 0.040%, clinical sensitivity and specificity for relapse was 74% and 87% respectively (51% and 98% for Flow-MRD ≥ 0.1%) by 'different-from-normal' analysis. Median relapse kinetics were 0.78 log 10 /month but significantly higher at 0.92 log 10 /month for FLT3-mutated AML. Computational (unsupervised) Flow-MRD (C-Flow-MRD) generated optimal MRD thresholds of 0.036% and 0.082% with equivalent clinical sensitivity to standard analysis. C-Flow-MRD-identified aberrancies in HLADRlow or CD34+CD38low (LSC-type) subpopulations contributed the greatest clinical accuracy (56% sensitivity, 90% specificity) and notably, by longitudinal profiling expanded rapidly within blasts in > 40% of 86 paired MRD and relapse samples. In conclusion, flow MRD surveillance can detect MRD relapse in high risk AML and its evaluation may be enhanced by computational analysis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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