A1 Refereed original research article in a scientific journal
Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting
Authors: S. Modvig, H. Hallböök, H. O. Madsen, S. Siitonen, S. Rosthøj, A. Tierens, V. Juvonen, L. T. N. Osnes, H. Vålerhaugen, M. Hultdin, R. Matuzeviciene, M. Stoskus, M. Marincevic, A. Lilleorg, M. Ehinger, U. Norén-Nystrøm, N. Toft, M. Taskinen, O. G. Jónsson, K. Pruunsild, G. Vaitkeviciene, K. Vettenranta, B. Lund, J. Abrahamsson, A. Porwit, K. Schmiegelow, H. V. Marquart
Publisher: SPRINGERNATURE
Publication year: 2020
Journal: Leukemia
Journal name in source: LEUKEMIA
Journal acronym: LEUKEMIA
Number of pages: 13
ISSN: 0887-6924
eISSN: 1476-5551
DOI: https://doi.org/10.1038/s41375-020-01100-5
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/51406079
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 x 10(-2) versus 5.2 x 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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