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

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

PY - 2019/6/1

Y1 - 2019/6/1

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

SN - 0887-6924

VL - 33

SP - 1324

EP - 1336

JO - Leukemia

JF - Leukemia

ER -