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Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia

The clinically ideal time point and optimal approach for the assessment of measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) are still inconclusive. We investigated the clinical value of multiparameter flow cytometry-based MRD (MFC MRD) after induction (n = 492) and two...

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Autores principales: Liu, Fu-Jia, Cheng, Wen-Yan, Lin, Xiao-Jing, Wang, Shi-Yang, Jiang, Tian-Yi, Ma, Ting-Ting, Zhu, Yong-Mei, Shen, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173083/
https://www.ncbi.nlm.nih.gov/pubmed/34094982
http://dx.doi.org/10.3389/fonc.2021.677833
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author Liu, Fu-Jia
Cheng, Wen-Yan
Lin, Xiao-Jing
Wang, Shi-Yang
Jiang, Tian-Yi
Ma, Ting-Ting
Zhu, Yong-Mei
Shen, Yang
author_facet Liu, Fu-Jia
Cheng, Wen-Yan
Lin, Xiao-Jing
Wang, Shi-Yang
Jiang, Tian-Yi
Ma, Ting-Ting
Zhu, Yong-Mei
Shen, Yang
author_sort Liu, Fu-Jia
collection PubMed
description The clinically ideal time point and optimal approach for the assessment of measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) are still inconclusive. We investigated the clinical value of multiparameter flow cytometry-based MRD (MFC MRD) after induction (n = 492) and two cycles of consolidation (n = 421). The latter time point was proved as a superior indicator with independent prognostic significance for both relapse-free survival (RFS, HR = 3.635, 95% CI: 2.433–5.431, P <0.001) and overall survival (OS: HR = 3.511, 95% CI: 2.191–5.626, P <0.001). Furthermore, several representative molecular MRD markers were compared with the MFC MRD. Both approaches can establish prognostic value in patients with NPM1 mutations, and FLT3, C-KIT, or N-RAS mutations involved in kinase-related signaling pathways, while the combination of both techniques further refined the risk stratification. The detection of RUNX1–RUNX1T1 fusion transcripts achieved a considerable net reclassification improvement in predicting the prognosis. Conversely, for patients with biallelic CEBPA or DNMT3A mutations, only the MFC method was recommended due to the poor prognostic discriminability in tracking mutant transcripts. In conclusion, this study demonstrated that the MFC MRD after two consolidation cycles independently predicted clinical outcomes, and the integration of MFC and molecular MRD should depend on different types of AML-related genetic lesions.
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spelling pubmed-81730832021-06-04 Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia Liu, Fu-Jia Cheng, Wen-Yan Lin, Xiao-Jing Wang, Shi-Yang Jiang, Tian-Yi Ma, Ting-Ting Zhu, Yong-Mei Shen, Yang Front Oncol Oncology The clinically ideal time point and optimal approach for the assessment of measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) are still inconclusive. We investigated the clinical value of multiparameter flow cytometry-based MRD (MFC MRD) after induction (n = 492) and two cycles of consolidation (n = 421). The latter time point was proved as a superior indicator with independent prognostic significance for both relapse-free survival (RFS, HR = 3.635, 95% CI: 2.433–5.431, P <0.001) and overall survival (OS: HR = 3.511, 95% CI: 2.191–5.626, P <0.001). Furthermore, several representative molecular MRD markers were compared with the MFC MRD. Both approaches can establish prognostic value in patients with NPM1 mutations, and FLT3, C-KIT, or N-RAS mutations involved in kinase-related signaling pathways, while the combination of both techniques further refined the risk stratification. The detection of RUNX1–RUNX1T1 fusion transcripts achieved a considerable net reclassification improvement in predicting the prognosis. Conversely, for patients with biallelic CEBPA or DNMT3A mutations, only the MFC method was recommended due to the poor prognostic discriminability in tracking mutant transcripts. In conclusion, this study demonstrated that the MFC MRD after two consolidation cycles independently predicted clinical outcomes, and the integration of MFC and molecular MRD should depend on different types of AML-related genetic lesions. Frontiers Media S.A. 2021-05-20 /pmc/articles/PMC8173083/ /pubmed/34094982 http://dx.doi.org/10.3389/fonc.2021.677833 Text en Copyright © 2021 Liu, Cheng, Lin, Wang, Jiang, Ma, Zhu and Shen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Liu, Fu-Jia
Cheng, Wen-Yan
Lin, Xiao-Jing
Wang, Shi-Yang
Jiang, Tian-Yi
Ma, Ting-Ting
Zhu, Yong-Mei
Shen, Yang
Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia
title Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia
title_full Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia
title_fullStr Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia
title_full_unstemmed Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia
title_short Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia
title_sort measurable residual disease detected by multiparameter flow cytometry and sequencing improves prediction of relapse and survival in acute myeloid leukemia
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173083/
https://www.ncbi.nlm.nih.gov/pubmed/34094982
http://dx.doi.org/10.3389/fonc.2021.677833
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