A1 Refereed original research article in a scientific journal

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




AuthorsS. Modvig, H. O. Madsen, S. M. Siitonen, S. Rosthøj, A. Tierens, V. Juvonen, L.T.N. Osnes, H. Vålerhaugen, M. Hultdin, I. Thörn, R. Matuzeviciene, M. Stoskus, M. Marincevic, L. Fogelstrand, A. Lilleorg, N. Toft, O. G. Jónsson, K. Pruunsild, G. Vaitkeviciene, K. Vettenranta, B. Lund, J. Abrahamsson, K. Schmiegelow, H. V. Marquart

PublisherNature Publishing Group

Publication year2019

JournalLeukemia

Volume33

Issue6

First page 1324

Last page1336

Number of pages13

ISSN0887-6924

DOIhttps://doi.org/10.1038/s41375-018-0307-6


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.



Last updated on 2024-26-11 at 22:44