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
. 2022 Jul 12;6(13):4006-4014.
doi: 10.1182/bloodadvances.2022007378.

High-sensitivity next-generation sequencing MRD assessment in ALL identifies patients at very low risk of relapse

Nicholas J Short  1 , Hagop Kantarjian  1 , Farhad Ravandi  1 , Marina Konopleva  1 , Nitin Jain  1 , Rashmi Kanagal-Shamanna  2 , Keyur P Patel  2 , Walid Macaron  1 , Tapan M Kadia  1 , Sa Wang  2 , Jeffrey L Jorgensen  2 , Joseph D Khoury  2 , Musa Yilmaz  1 , Partow Kebriaei  3 , Koichi Takahashi  1 , Guillermo Garcia-Manero  1 , Naval Daver  1 , Sean M Post  1 , Xuelin Huang  4 , Steven M Kornblau  1 , Sara Pelletier  1 , Wilmer Flores  1 , Jairo Matthews  1 , Rebecca Garris  1 , Elias Jabbour  1
Affiliations

High-sensitivity next-generation sequencing MRD assessment in ALL identifies patients at very low risk of relapse

Nicholas J Short et al. Blood Adv. .

Abstract

Measurable residual disease (MRD) is highly prognostic for relapse and overall survival (OS) in acute lymphoblastic leukemia (ALL), although many patients with apparent "MRD negativity" by standard assays still relapse. We evaluated the clinical impact of a highly sensitive next-generation sequencing (NGS) MRD assay in 74 adults with ALL undergoing frontline therapy. Among remission samples that were MRD negative by multiparameter flow cytometry (MFC), 46% were MRD+ by the NGS assay. After 1 cycle of induction chemotherapy, MRD negativity by MFC at a sensitivity of 1 × 10-4 and NGS at a sensitivity of 1 × 10-6 was achieved in 66% and 23% of patients, respectively. The 5-year cumulative incidence of relapse (CIR) among patients who achieved MRD negativity by MFC at complete remission (CR) was 29%; in contrast, no patients who achieved early MRD negativity by NGS relapsed, and their 5-year OS was 90%. NGS MRD negativity at CR was associated with significantly decreased risk of relapse compared with MRD positivity (5-year CIR, 0% vs 45%, respectively; P = .04). Among patients who were MRD negative by MFC, detection of low levels of MRD by NGS identified patients who still had a significant risk of relapse (5-year CIR, 39%). Early assessment of MRD using a highly sensitive NGS assay adds clinically relevant prognostic information to standard MFC-based approaches and can identify patients with ALL undergoing frontline therapy who have a very low risk of relapse and excellent long-term survival.

PubMed Disclaimer

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Flowchart of MRD response by MFC and NGS at various time points. Discordance rates were calculated including only patients who were assessed as either MRD-positive or -negative by NGS at a sensitivity of 10−6 and excluding patients who were MRD indeterminate by NGS at 10−6. One MRD sample at time of CR and at 1.5 to 3 months was indeterminate by MFC; in both cases, MRD was detected by the NGS assay. MRDpos, MRD+; MRDneg, MRD−; MRDind, MRD indeterminate.
Figure 2.
Figure 2.
Outcomes by MRD status by NGS at 10−6 sensitivity at the time of CR. (A) Cumulative incidence of relapse and (B) OS. MRDpos, MRD+; MRDneg, MRD−.
Figure 3.
Figure 3.
Outcomes by MRD status by NGS at 10−6 sensitivity and by MFC at the time of CR. (A) Cumulative incidence of relapse and (B) OS. MRDpos, MRD+; MRDneg, MRD−.
Figure 4.
Figure 4.
Outcomes by MRD status by NGS at 10−6 sensitivity at the time of CR in nontransplanted patients. (A) Cumulative incidence of relapse and (B) OS. MRDpos, MRD+; MRDneg, MRD−.
See this image and copyright information in PMC

References

    1. Patel B, Rai L, Buck G, et al. . Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993. Br J Haematol. 2010;148(1):80-89. - PubMed
    1. Gökbuget N, Kneba M, Raff T, et al. ; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia . Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012;120(9):1868-1876. - PubMed
    1. Beldjord K, Chevret S, Asnafi V, et al. ; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) . Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood. 2014;123(24):3739-3749. - PubMed
    1. Ribera JM, Oriol A, Morgades M, et al. . Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial. J Clin Oncol. 2014;32(15):1595-1604. - PubMed
    1. Dhédin N, Huynh A, Maury S, et al. ; GRAALL group . Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia. Blood. 2015;125(16):2486-2496, quiz 2586. - PubMed

Publication types

MeSH terms