Modvig, S.; Hallböök, H.; Madsen, H. O.; Siitonen, S.; Rosthoj, S.; Tierens, A.; Juvonen, V.; Osnes, L. T. N.; Valerhaugen, H.; Hultdin, M.; Matuzeviciene, R.; Stoskus, M.; Marincevic, M.; Lilleorg, A.; Ehinger, M.; Noren-Nystrom, U.; Toft, N.; Taskinen, M.; Jonsson, O. G.; Pruunsild, K.; Vaitkeviciene, G.; Vettenranta, K.; Lund, B.; Abrahamsson, J.; Porwit, A.; Schmiegelow, K.; Marquart, H. V.
(2021)
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.