Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia
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Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia. / Modvig, S; Madsen, H O; Siitonen, S M; Rosthøj, S.; Tierens, A; Juvonen, V; Osnes, L T N; Vålerhaugen, H; Hultdin, M; Thörn, I; Matuzeviciene, R; Stoskus, M; Marincevic, M; Fogelstrand, L; Lilleorg, A; Toft, N; Jónsson, O G; Pruunsild, K; Vaitkeviciene, G; Vettenranta, K; Lund, B; Abrahamsson, J; Schmiegelow, K.; Marquart, H V.
I: Leukemia, Bind 33, 2019, s. 1324–1336.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia
AU - Modvig, S
AU - Madsen, H O
AU - Siitonen, S M
AU - Rosthøj, S.
AU - Tierens, A
AU - Juvonen, V
AU - Osnes, L T N
AU - Vålerhaugen, H
AU - Hultdin, M
AU - Thörn, I
AU - Matuzeviciene, R
AU - Stoskus, M
AU - Marincevic, M
AU - Fogelstrand, L
AU - Lilleorg, A
AU - Toft, N
AU - Jónsson, O G
AU - Pruunsild, K
AU - Vaitkeviciene, G
AU - Vettenranta, K
AU - Lund, B
AU - Abrahamsson, J
AU - Schmiegelow, K.
AU - Marquart, H V
N1 - Correction: Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia. DOI:10.1038/s41375-019-0672-9
PY - 2019
Y1 - 2019
N2 - Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10-3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4-9.0, p = 0.008) for day 29 FCM-MRD ≥ 10-3 and 5.6 (95% CI 2.0-16, p = 0.001) for PCR-MRD ≥ 10-3 compared with MRD < 10-3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10-4-<10-3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10-4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10-4 had a cumulative incidence of relapse of 2.3% (95% CI 0-6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.
AB - Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10-3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4-9.0, p = 0.008) for day 29 FCM-MRD ≥ 10-3 and 5.6 (95% CI 2.0-16, p = 0.001) for PCR-MRD ≥ 10-3 compared with MRD < 10-3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10-4-<10-3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10-4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10-4 had a cumulative incidence of relapse of 2.3% (95% CI 0-6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.
U2 - 10.1038/s41375-018-0307-6
DO - 10.1038/s41375-018-0307-6
M3 - Journal article
C2 - 30552401
VL - 33
SP - 1324
EP - 1336
JO - Leukemia
JF - Leukemia
SN - 0887-6924
ER -
ID: 218655636