Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May 25;5(10):2456-2466.
doi: 10.1182/bloodadvances.2020003738.

Clinical implications of sequential MRD monitoring by NGS at 2 time points after chemotherapy in patients with AML

Cheng-Hong Tsai  1   2 , Jih-Luh Tang  3   4 , Feng-Ming Tien  3 , Yuan-Yeh Kuo  4 , Dung-Chi Wu  2 , Chien-Chin Lin  1   5   6 , Mei-Hsuan Tseng  1 , Yen-Ling Peng  1 , Mei-Fang Hou  1   7 , Yi-Kuang Chuang  4 , Ming-Chih Liu  8 , Chia-Wen Liu  8 , Ming Yao  1 , Liang-In Lin  9 , Wen-Chien Chou  1   5 , Chien-Yu Chen  2   10 , Hsin-An Hou  1 , Hwei-Fang Tien  1
Affiliations

Clinical implications of sequential MRD monitoring by NGS at 2 time points after chemotherapy in patients with AML

Cheng-Hong Tsai et al. Blood Adv. .

Abstract

Next-generation sequencing (NGS) has been applied to measurable/minimal residual disease (MRD) monitoring after induction chemotherapy in patients with acute myeloid leukemia (AML), but the optimal time point for the test remains unclear. In this study, we aimed to investigate the clinical significance of NGS MRD at 2 different time points. We performed targeted NGS of 54 genes in bone marrow cells serially obtained at diagnosis, first complete remission (first time point), and after the first consolidation chemotherapy (second time point) from 335 de novo AML patients. Excluding DNMT3A, TET2, and ASXL1 mutations, which are commonly present in individuals with clonal hematopoiesis of indeterminate potential, MRD could be detected in 46.4% of patients at the first time point (MRD1st), and 28.9% at the second time point (MRD2nd). The patients with detectable NGS MRD at either time point had a significantly higher cumulative incidence of relapse and shorter relapse-free survival and overall survival. In multivariate analysis, MRD1st and MRD2nd were both independent poor prognostic factors. However, the patients with positive MRD1st but negative MRD2nd had a similar good prognosis as those with negative MRD at both time points. The incorporation of multiparameter flow cytometry and NGS MRD revealed that the presence of NGS MRD predicted poorer prognosis among the patients without detectable MRD by multiparameter flow cytometry at the second time point but not the first time point. In conclusion, the presence of NGS MRD, especially after the first consolidation therapy, can help predict the clinical outcome of AML patients.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: H.-F.T., W.-C.C., and H.-A.H. received research funding from Celgene. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Prognostic impact of NGS MRD. (A-C) The CIR, RFS, and OS of patients stratified by the MRD status, detected at either the first or second time point. Patients with detectable MRD had significantly poorer outcomes than those without MRD. (D-I) The CIR, RFS, and OS of patients stratified by the MRD status at the first (D,F,H) and second time points (E,G,I). The difference in outcome remained significant at both time points. NE, not estimated.
Figure 2.
Figure 2.
Prognostic significance of different statuses of NGS MRD at the first and second time points. The Kaplan-Meier curves stratified by the NGS MRD status for CIR (A), RFS (B), and OS (C). The MRD2nd− patients, either MRD1st− or MRD1st+, had a better outcome than MRD2nd+ patients. The MRD1st−MRD2nd+ and MRD1st+MRD2nd+ patients had a similar dismal prognosis, whereas MRD1st+MRD2nd− patients had a good prognosis similar to that of MRD1st−MRD2nd− patients.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Papaemmanuil E, Gerstung M, Bullinger L, et al. . Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209-2221. - PMC - PubMed
    1. Schuurhuis GJ, Heuser M, Freeman S, et al. . Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2018;131(12):1275-1291. - PMC - PubMed
    1. Walter RB, Buckley SA, Pagel JM, et al. . Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission. Blood. 2013;122(10):1813-1821. - PMC - PubMed
    1. Ivey A, Hills RK, Simpson MA, et al. ; UK National Cancer Research Institute AML Working Group . Assessment of minimal residual disease in standard-risk AML. N Engl J Med. 2016;374(5):422-433. - PubMed
    1. Hourigan CS, Gale RP, Gormley NJ, Ossenkoppele GJ, Walter RB. Measurable residual disease testing in acute myeloid leukaemia. Leukemia. 2017;31(7):1482-1490. - PubMed

Publication types

MeSH terms