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Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting

Modvig, S. ; Hallböök, H. ; Madsen, H. O. ; Siitonen, S. ; Rosthøj, S. ; Tierens, A. ; Juvonen, V. ; Osnes, L. T.N. ; Vålerhaugen, H. and Hultdin, M. , et al. (2021) In Leukemia 35(7). p.1894-1906
Abstract

PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse... (More)

PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p < 0.0001), 29 (HzR 2.7, p < 0.0001), and 79 (HzR 3.5, p < 0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR5y adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4 × 10−2 versus 5.2 × 10−3, p < 0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR5y = 3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD > 10−4 associated with a CIR5y = 22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Leukemia
volume
35
issue
7
pages
13 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:33318611
  • scopus:85105834373
ISSN
0887-6924
DOI
10.1038/s41375-020-01100-5
language
English
LU publication?
yes
id
7bab7e42-4df7-4f74-8d4f-140962a25921
date added to LUP
2021-12-23 14:43:02
date last changed
2024-04-20 18:19:44
@article{7bab7e42-4df7-4f74-8d4f-140962a25921,
  abstract     = {{<p>PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR<sub>5y</sub>) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p &lt; 0.0001), 29 (HzR 2.7, p &lt; 0.0001), and 79 (HzR 3.5, p &lt; 0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR<sub>5y</sub> adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4 × 10<sup>−2</sup> versus 5.2 × 10<sup>−3</sup>, p &lt; 0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR<sub>5y</sub> = 3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD &gt; 10<sup>−4</sup> associated with a CIR<sub>5y</sub> = 22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.</p>}},
  author       = {{Modvig, S. and Hallböök, H. and Madsen, H. O. and Siitonen, S. and Rosthøj, S. and Tierens, A. and Juvonen, V. and Osnes, L. T.N. and Vålerhaugen, H. and Hultdin, M. and Matuzeviciene, R. and Stoskus, M. and Marincevic, M. and Lilleorg, A. and Ehinger, M. and Norén-Nystrøm, U. and Toft, N. and Taskinen, M. and Jónsson, O. G. and Pruunsild, K. and Vaitkeviciene, G. and Vettenranta, K. and Lund, B. and Abrahamsson, J. and Porwit, A. and Schmiegelow, K. and Marquart, H. V.}},
  issn         = {{0887-6924}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1894--1906}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Leukemia}},
  title        = {{Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting}},
  url          = {{http://dx.doi.org/10.1038/s41375-020-01100-5}},
  doi          = {{10.1038/s41375-020-01100-5}},
  volume       = {{35}},
  year         = {{2021}},
}