TY - JOUR
T1 - Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting
AU - Modvig, S.
AU - Hallböök, H.
AU - Madsen, H. O.
AU - Siitonen, S.
AU - Rosthøj, S.
AU - Tierens, A.
AU - Juvonen, V.
AU - Osnes, L. T.N.
AU - Vålerhaugen, H.
AU - Hultdin, M.
AU - Matuzeviciene, R.
AU - Stoskus, M.
AU - Marincevic, M.
AU - Lilleorg, A.
AU - Ehinger, M.
AU - Norén-Nystrøm, U.
AU - Toft, N.
AU - Taskinen, M.
AU - Jónsson, O. G.
AU - Pruunsild, K.
AU - Vaitkeviciene, G.
AU - Vettenranta, K.
AU - Lund, B.
AU - Abrahamsson, J.
AU - Porwit, A.
AU - Schmiegelow, K.
AU - Marquart, H. V.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1038/s41375-020-01100-5
DO - 10.1038/s41375-020-01100-5
M3 - Article
C2 - 33318611
AN - SCOPUS:85105834373
SN - 0887-6924
VL - 35
SP - 1894
EP - 1906
JO - Leukemia
JF - Leukemia
IS - 7
ER -
