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

Journal article
Authors S 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
Linda Fogelstrand
A Lilleorg
N Toft
O G Jónsson
K Pruunsild
G Vaitkeviciene
K Vettenranta
B Lund
Jonas Abrahamsson
K Schmiegelow
H V Marquart
Published in Leukemia
Volume 33
Issue 6
Pages 1324-1336
ISSN 1476-5551
Publication year 2019
Published at Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Pages 1324-1336
Language en
Subject categories Pediatrics


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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