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Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia.

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Authors
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
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Issue Date
2019-06

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Citation
Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia. 2019, 33(6):1324-1336 Leukemia
Abstract
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.
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https://www.nature.com/articles/s41375-018-0307-6
https://ovidsp.dc1.ovid.com/sp-3.33.0b/ovidweb.cgi?QS2=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
https://search.proquest.com/publication/30521
ae974a485f413a2113503eed53cd6c53
10.1038/s41375-018-0307-6
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