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Cell-free DNA measurable residual disease as a predictor of postallogeneic hematopoietic cell transplant outcomes

The measurable residual disease (MRD) assessment provides an attractive predictor of allogeneic hematopoietic cell transplnat (alloHCT) outcomes. Cell-free DNA (cfDNA) has been applied to diagnosis, early detection, and disease burden monitoring in various tumors, but its utility as an MRD test in m...

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Autores principales: Pasca, Sergiu, Guo, Matthew Z., Wang, Shiyu, Stokvis, Kristin, Shedeck, Audra, Pallavajjala, Aparna, Shams, Cynthia, Pallavajjala, Roshni, DeZern, Amy E., Varadhan, Ravi, Gocke, Christopher D., Jones, Richard J., Gondek, Lukasz P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Hematology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448421/
https://www.ncbi.nlm.nih.gov/pubmed/37276081
http://dx.doi.org/10.1182/bloodadvances.2023010416
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author Pasca, Sergiu
Guo, Matthew Z.
Wang, Shiyu
Stokvis, Kristin
Shedeck, Audra
Pallavajjala, Aparna
Shams, Cynthia
Pallavajjala, Roshni
DeZern, Amy E.
Varadhan, Ravi
Gocke, Christopher D.
Jones, Richard J.
Gondek, Lukasz P.
author_facet Pasca, Sergiu
Guo, Matthew Z.
Wang, Shiyu
Stokvis, Kristin
Shedeck, Audra
Pallavajjala, Aparna
Shams, Cynthia
Pallavajjala, Roshni
DeZern, Amy E.
Varadhan, Ravi
Gocke, Christopher D.
Jones, Richard J.
Gondek, Lukasz P.
author_sort Pasca, Sergiu
collection PubMed
description The measurable residual disease (MRD) assessment provides an attractive predictor of allogeneic hematopoietic cell transplnat (alloHCT) outcomes. Cell-free DNA (cfDNA) has been applied to diagnosis, early detection, and disease burden monitoring in various tumors, but its utility as an MRD test in myeloid malignancies has not been systematically evaluated. We sought to determine the differential sensitivity between bone marrow (BM) and cfDNA MRD and to assess the effect of cfDNA MRD on alloHCT outcomes. The technical and clinical validation cohorts, including 82 patients participating in clinical trials (Bone Marrow Transplant Clinical Trials Network-0201 and 0402), were used. Ultradeep error-corrected targeted sequencing was performed on plasma and BM-derived DNA. We demonstrated that 94.6% (range, 93.9-95.3) of cfDNA was derived from hematopoietic tissue. The mutant allele fraction was congruent between BM and cfDNA (rho = 0.8; P < .0001); however, cfDNA seemed to be more sensitive in detecting clones with a variant allele frequency (VAF) of <0.26%. cfDNA-MRD clearance by day 90 after alloHCT (D90) was associated with improved relapse-free survival (RFS, median survival not reached vs 5.5 months; P < .0001) and overall survival (OS, median survival not reached vs 7.3 months; P < .0001) when compared with patients with persistent MRD. Irrespective of pre-alloHCT MRD, D90 cfDNA MRD was associated with inferior 2-year OS (16.7% vs 84.8%; P < .0001) and RFS (16.7% vs 80.7%; P < .0001). cfDNA seems to be an accurate, minimally invasive alternative to BM aspirates in MRD assessment and confers important prognostic implications in patients with myeloid malignancies undergoing alloHCT.
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spelling pubmed-104484212023-08-25 Cell-free DNA measurable residual disease as a predictor of postallogeneic hematopoietic cell transplant outcomes Pasca, Sergiu Guo, Matthew Z. Wang, Shiyu Stokvis, Kristin Shedeck, Audra Pallavajjala, Aparna Shams, Cynthia Pallavajjala, Roshni DeZern, Amy E. Varadhan, Ravi Gocke, Christopher D. Jones, Richard J. Gondek, Lukasz P. Blood Adv Hematopoiesis and Stem Cells The measurable residual disease (MRD) assessment provides an attractive predictor of allogeneic hematopoietic cell transplnat (alloHCT) outcomes. Cell-free DNA (cfDNA) has been applied to diagnosis, early detection, and disease burden monitoring in various tumors, but its utility as an MRD test in myeloid malignancies has not been systematically evaluated. We sought to determine the differential sensitivity between bone marrow (BM) and cfDNA MRD and to assess the effect of cfDNA MRD on alloHCT outcomes. The technical and clinical validation cohorts, including 82 patients participating in clinical trials (Bone Marrow Transplant Clinical Trials Network-0201 and 0402), were used. Ultradeep error-corrected targeted sequencing was performed on plasma and BM-derived DNA. We demonstrated that 94.6% (range, 93.9-95.3) of cfDNA was derived from hematopoietic tissue. The mutant allele fraction was congruent between BM and cfDNA (rho = 0.8; P < .0001); however, cfDNA seemed to be more sensitive in detecting clones with a variant allele frequency (VAF) of <0.26%. cfDNA-MRD clearance by day 90 after alloHCT (D90) was associated with improved relapse-free survival (RFS, median survival not reached vs 5.5 months; P < .0001) and overall survival (OS, median survival not reached vs 7.3 months; P < .0001) when compared with patients with persistent MRD. Irrespective of pre-alloHCT MRD, D90 cfDNA MRD was associated with inferior 2-year OS (16.7% vs 84.8%; P < .0001) and RFS (16.7% vs 80.7%; P < .0001). cfDNA seems to be an accurate, minimally invasive alternative to BM aspirates in MRD assessment and confers important prognostic implications in patients with myeloid malignancies undergoing alloHCT. The American Society of Hematology 2023-06-07 /pmc/articles/PMC10448421/ /pubmed/37276081 http://dx.doi.org/10.1182/bloodadvances.2023010416 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Hematopoiesis and Stem Cells
Pasca, Sergiu
Guo, Matthew Z.
Wang, Shiyu
Stokvis, Kristin
Shedeck, Audra
Pallavajjala, Aparna
Shams, Cynthia
Pallavajjala, Roshni
DeZern, Amy E.
Varadhan, Ravi
Gocke, Christopher D.
Jones, Richard J.
Gondek, Lukasz P.
Cell-free DNA measurable residual disease as a predictor of postallogeneic hematopoietic cell transplant outcomes
title Cell-free DNA measurable residual disease as a predictor of postallogeneic hematopoietic cell transplant outcomes
title_full Cell-free DNA measurable residual disease as a predictor of postallogeneic hematopoietic cell transplant outcomes
title_fullStr Cell-free DNA measurable residual disease as a predictor of postallogeneic hematopoietic cell transplant outcomes
title_full_unstemmed Cell-free DNA measurable residual disease as a predictor of postallogeneic hematopoietic cell transplant outcomes
title_short Cell-free DNA measurable residual disease as a predictor of postallogeneic hematopoietic cell transplant outcomes
title_sort cell-free dna measurable residual disease as a predictor of postallogeneic hematopoietic cell transplant outcomes
topic Hematopoiesis and Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448421/
https://www.ncbi.nlm.nih.gov/pubmed/37276081
http://dx.doi.org/10.1182/bloodadvances.2023010416
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