Next‐generation sequencing‐defined minimal residual disease before stem cell transplantation predicts acute myeloid leukemia relapse

In acute myeloid leukemia (AML), the assessment of post‐treatment minimal residual disease (MRD) may inform a more effective management approach. We investigated the prognostic utility of next‐generation sequencing (NGS)‐based MRD detection undertaken before hematopoietic stem cell transplantation (...

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Vydáno v:American journal of hematology Ročník 94; číslo 8; s. 902 - 912
Hlavní autoři: Press, Richard D., Eickelberg, Garrett, Froman, Allison, Yang, Fei, Stentz, Alex, Flatley, Ellen M., Fan, Guang, Lim, Jeong Y., Meyers, Gabrielle, Maziarz, Richard T., Cook, Rachel J.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Hoboken, USA John Wiley & Sons, Inc 01.08.2019
Wiley Subscription Services, Inc
Témata:
Acute myeloid leukemia
Adult
Aged
Cohort Studies
Female
Flow cytometry
Hematology
Hematopoietic Stem Cell Transplantation
Hematopoietic stem cells
High-Throughput Nucleotide Sequencing - methods
Humans
Leukemia
Leukemia, Myeloid, Acute - epidemiology
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - therapy
Male
Middle Aged
Minimal residual disease
Mutation
Myeloid leukemia
Neoplasm, Residual - epidemiology
Neoplasm, Residual - genetics
Neoplasm, Residual - therapy
p53 Protein
Recurrence
Retrospective Studies
Stem cell transplantation
Stem cells
Transplantation Conditioning - methods
Transplants & implants
ISSN:0361-8609, 1096-8652, 1096-8652
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Shrnutí:In acute myeloid leukemia (AML), the assessment of post‐treatment minimal residual disease (MRD) may inform a more effective management approach. We investigated the prognostic utility of next‐generation sequencing (NGS)‐based MRD detection undertaken before hematopoietic stem cell transplantation (HSCT). Forty‐two AML subjects underwent serial disease monitoring both by standard methods, and a targeted 42‐gene NGS assay, able to detect leukemia‐specific mutant alleles (with >0.5% VAF) (mean 5.1 samples per subject). The prognostic relevance of any persisting diagnostic mutation before transplant (≤27 days) was assessed during 22.1 months (median) of post‐transplant follow‐up. The sensitivity of the NGS assay (27 MRD‐positive subjects) exceeded that of the non‐molecular methods (morphology, FISH, and flow cytometry) (11 positive subjects). Only one of the 13 subjects who relapsed after HSCT was NGS MRD‐negative (92% assay sensitivity). The cumulative incidence of post‐transplant leukemic relapse was significantly higher in the pre‐transplant NGS MRD‐positive (vs MRD‐negative) subjects (P = .014). After adjusting for TP53 mutation and transplant conditioning regimen, NGS MRD‐positivity retained independent prognostic significance for leukemic relapse (subdistribution hazard ratio = 7.3; P = .05). The pre‐transplant NGS MRD‐positive subjects also had significantly shortened progression‐free survival (P = .038), and marginally shortened overall survival (P = .068). In patients with AML undergoing HSCT, the pre‐transplant persistence of NGS‐defined MRD imparts a significant, sensitive, strong, and independent increased risk for subsequent leukemic relapse and death. Given that NGS can simultaneously detect multiple leukemia‐associated mutations, it can be used in the majority of AML patients to monitor disease burdens and inform treatment decisions.
Bibliografie:Funding information
Knight Cancer Institute; OHSU Department of Pathology
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ISSN:0361-8609
1096-8652
1096-8652
DOI:10.1002/ajh.25514