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
. 2024 Jul 18;144(3):253-261.
doi: 10.1182/blood.2023023699.

How I use next-generation sequencing-MRD to plan approach and prevent relapse after HCT for children and adults with ALL

Lori Muffly  1 , Emily C Liang  2 , J Gregory Dolan  3 , Michael A Pulsipher  3   4
Affiliations

How I use next-generation sequencing-MRD to plan approach and prevent relapse after HCT for children and adults with ALL

Lori Muffly et al. Blood. .

Abstract

Measurable residual disease (MRD) evaluation by multiparameter flow cytometry (MFC) or quantitative polymerase chain reaction methods is an established standard of care for assessing risk of relapse before or after hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL). Next-generation sequencing (NGS)-MRD has emerged as a highly effective approach that allows for the detection of lymphoblasts at a level of <1 in 106 nucleated cells, increasing sensitivity of ALL detection by 2 to 3 logs. Early studies have shown superior results compared with MFC and suggest that NGS-MRD may allow for the determination of patients in whom reduced toxicity transplant preparative approaches could be deployed without sacrificing outcomes. Many centers/study groups have implemented immune modulation approaches based on MRD measurements that have resulted in improved outcomes. Challenges remain with NGS-MRD, because it is not commercially available in many countries, and interpretation of results can be complex. Through patient case review, discussion of relevant studies, and detailed expert opinion, we share our approach to NGS-MRD testing before and after HCT in pediatric and adult ALL. Improved pre-HCT risk classification and post-HCT monitoring for relapse in bone marrow and less invasive peripheral blood monitoring by NGS-MRD may lead to alternative approaches to prevent relapse in patients undergoing this challenging procedure.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: L.M. reports advisory board fees from Kite, Autolus, Vor, and Cargo; research support from Jasper, Kite, Adaptive Biotechnologies, Bristol Myers Squibb, Astellas, Wugen, and Vor; honoraria from Kite; and consultancy from Astellas. M.A.P. reports advisory board fees from Pfizer, Cargo, Novartis, GentiBio, Bluebird, and Vertex; steering committee membership for Novartis and Autolus; and research support from Miltenyi and Adaptive Biotechnologies. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Stepwise approach to identification of clonal dominant sequence(s) and subsequent MRD tracking.
Figure 2.
Figure 2.
Associations between pre-HCT NGS-MRD and post-HCT relapse. In children and young adults with ALL (any level of NGS-MRD is considered positive) (A) and adult patients with ALL (B).
Figure 3.
Figure 3.
Approach to HCT for ALL in children and adults based on pre- and post-HCT NGS-MRD.
See this image and copyright information in PMC

References

    1. US Food and Drug Administration FDA authorizes first next generation sequencing-based test to detect very low levels of remaining cancer cells in patients with acute lymphoblastic leukemia or multiple myeloma. https://www.fda.gov/news-events/press-announcements/fda-authorizes-first... Released 18 September 2018.
    1. Saygin C, Cannova J, Stock W, Muffly L. Measurable residual disease in acute lymphoblastic leukemia: methods and clinical context in adult patients. Haematologica. 2022;107(12):2783–2793. - PMC - PubMed
    1. Pulsipher MA, Carlson C, Langholz B, et al. IgH-V(D)J NGS-MRD measurement pre- and early post-allotransplant defines very low- and very high-risk ALL patients. Blood. 2015;125(22):3501–3508. - PMC - PubMed
    1. Wood B, Wu D, Crossley B, et al. Measurable residual disease detection by high-throughput sequencing improves risk stratification for pediatric B-ALL. Blood. 2018;131(12):1350–1359. - PMC - PubMed
    1. Logan AC, Vashi N, Faham M, et al. Immunoglobulin and T cell receptor gene high-throughput sequencing quantifies minimal residual disease in acute lymphoblastic leukemia and predicts post-transplantation relapse and survival. Biol Blood Marrow Transplant. 2014;20(9):1307–1313. - PMC - PubMed

Publication types

MeSH terms