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Minimal residual disease assessed with deep sequencing of NPM1 mutations predicts relapse after allogeneic stem cell transplant in AML

Delsing Malmberg, Erik ; Johansson Alm, Sofie ; Nicklasson, Malin ; Lazarevic, Vladimir LU ; Ståhlman, Sara ; Samuelsson, Tore ; Lenhoff, Stig LU ; Asp, Julia ; Ehinger, Mats LU and Palmqvist, Lars , et al. (2019) In Leukemia and Lymphoma 60(2). p.409-417
Abstract

Mutations in NPM1 can be used for minimal residual disease (MRD) analysis in acute myeloid leukemia (AML). We here applied a newly introduced method, deep sequencing, allowing for simultaneous analysis of all recurrent NPM1 insertions and thus constituting an attractive alternative to multiple PCRs for the clinical laboratory. We retrospectively used deep sequencing for measurement of MRD pre- and post-allogeneic hematopoietic stem cell transplantation (alloHCT). For 29 patients in morphological remission at the time of alloHCT, the effect of deep sequencing MRD on outcome was assessed. MRD positivity was defined as variant allele frequency ≥0.02%. Post-transplant MRD status was significantly and independently associated with clinical... (More)

Mutations in NPM1 can be used for minimal residual disease (MRD) analysis in acute myeloid leukemia (AML). We here applied a newly introduced method, deep sequencing, allowing for simultaneous analysis of all recurrent NPM1 insertions and thus constituting an attractive alternative to multiple PCRs for the clinical laboratory. We retrospectively used deep sequencing for measurement of MRD pre- and post-allogeneic hematopoietic stem cell transplantation (alloHCT). For 29 patients in morphological remission at the time of alloHCT, the effect of deep sequencing MRD on outcome was assessed. MRD positivity was defined as variant allele frequency ≥0.02%. Post-transplant MRD status was significantly and independently associated with clinical outcome; 3-year relapse-free survival 20% vs 85% (p <.001), HR 45 (95% CI 2–1260), and overall survival 20% vs 89% (p <.001), HR 49 (95% CI 2–1253). Thus, the new methodology deep sequencing is an applicable and predictive tool for MRD assessment in AML.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Acute myeloid leukemia, massively parallel sequencing, minimal residual disease
in
Leukemia and Lymphoma
volume
60
issue
2
pages
409 - 417
publisher
Taylor & Francis
external identifiers
  • pmid:30068244
  • scopus:85052104566
ISSN
1042-8194
DOI
10.1080/10428194.2018.1485910
language
English
LU publication?
yes
id
59c3f221-31bd-4e9f-901c-51737e353cad
date added to LUP
2018-10-05 13:28:11
date last changed
2024-04-01 11:35:59
@article{59c3f221-31bd-4e9f-901c-51737e353cad,
  abstract     = {{<p>Mutations in NPM1 can be used for minimal residual disease (MRD) analysis in acute myeloid leukemia (AML). We here applied a newly introduced method, deep sequencing, allowing for simultaneous analysis of all recurrent NPM1 insertions and thus constituting an attractive alternative to multiple PCRs for the clinical laboratory. We retrospectively used deep sequencing for measurement of MRD pre- and post-allogeneic hematopoietic stem cell transplantation (alloHCT). For 29 patients in morphological remission at the time of alloHCT, the effect of deep sequencing MRD on outcome was assessed. MRD positivity was defined as variant allele frequency ≥0.02%. Post-transplant MRD status was significantly and independently associated with clinical outcome; 3-year relapse-free survival 20% vs 85% (p &lt;.001), HR 45 (95% CI 2–1260), and overall survival 20% vs 89% (p &lt;.001), HR 49 (95% CI 2–1253). Thus, the new methodology deep sequencing is an applicable and predictive tool for MRD assessment in AML.</p>}},
  author       = {{Delsing Malmberg, Erik and Johansson Alm, Sofie and Nicklasson, Malin and Lazarevic, Vladimir and Ståhlman, Sara and Samuelsson, Tore and Lenhoff, Stig and Asp, Julia and Ehinger, Mats and Palmqvist, Lars and Brune, Mats and Fogelstrand, Linda}},
  issn         = {{1042-8194}},
  keywords     = {{Acute myeloid leukemia; massively parallel sequencing; minimal residual disease}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{409--417}},
  publisher    = {{Taylor & Francis}},
  series       = {{Leukemia and Lymphoma}},
  title        = {{Minimal residual disease assessed with deep sequencing of NPM1 mutations predicts relapse after allogeneic stem cell transplant in AML}},
  url          = {{http://dx.doi.org/10.1080/10428194.2018.1485910}},
  doi          = {{10.1080/10428194.2018.1485910}},
  volume       = {{60}},
  year         = {{2019}},
}