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

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 PruunsildG Vaitkeviciene, K Vettenranta, B Lund, J Abrahamsson, A Porwit, K Schmiegelow, H V Marquart

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Publication statusPublished - 14 Dec 2020

Other keywords

  • Flow Cytometry


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