Measurable residual disease (MRD) evaluation by multiparameter flow cytometry (MFC) or quantitative PCR methods is an established standard of care for assessing risk of relapse prior to 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 detection of lymphoblasts at a level of fewer than 1 in 106 nucleated cells, increasing sensitivity of ALL detection by 2-3 logs. Early studies have shown superior results compared with MFC and suggest that NGS-MRD may allow 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, as 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 prior to 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. -
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Review Article|
May 10, 2024
How I Use Next Generation Sequencing-MRD to Plan Approach and Prevent Relapse after HCT for Children and Adults with ALL
Lori Muffly,
Lori Muffly
Stanford University, Stanford, California, United States
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Emily C. Liang,
Emily C. Liang
Fred Hutchinson Cancer Center, Seattle, Washington, United States
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J. Gregory Dolan,
J. Gregory Dolan
Huntsman Cancer Institute/Intermountain Primary Chlldren's Hospital, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, Utah, United States
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Michael A Pulsipher
Huntsman Cancer Institute/Intermountain Primary Chlldren's Hospital, Spencer Fox Eccles School of Medicine, University of Utah., Salt Lake City, Utah, United States
* Corresponding Author; email: michael.pulsipher@hci.utah.edu
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Blood blood.2023023699.
Article history
Submitted:
February 29, 2024
Revision Received:
April 11, 2024
Accepted:
April 24, 2024
Citation
Lori Muffly, Emily C. Liang, J. Gregory Dolan, Michael A Pulsipher; How I Use Next Generation Sequencing-MRD to Plan Approach and Prevent Relapse after HCT for Children and Adults with ALL. Blood 2024; blood.2023023699. doi: https://doi.org/10.1182/blood.2023023699
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