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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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Modvig, S, Madsen, HO, Siitonen, SM, Rosthøj, S, Tierens, A, Juvonen, V, Osnes, LTN, Vålerhaugen, H, Hultdin, M, Thörn, I, Matuzeviciene, R, Stoskus, M, Marincevic, M, Fogelstrand, L, Lilleorg, A, Toft, N, Jónsson, OG, Pruunsild, K, Vaitkeviciene, G, Vettenranta, K, Lund, B, Abrahamsson, J, Schmiegelow, K & Marquart, HV 2019, 'Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia' Leukemia, bind 33, nr. 6, s. 1324-1336. https://doi.org/10.1038/s41375-018-0307-6

APA

CBE

Modvig S, Madsen HO, Siitonen SM, Rosthøj S, Tierens A, Juvonen V, Osnes LTN, Vålerhaugen H, Hultdin M, Thörn I, Matuzeviciene R, Stoskus M, Marincevic M, Fogelstrand L, Lilleorg A, Toft N, Jónsson OG, Pruunsild K, Vaitkeviciene G, Vettenranta K, Lund B, Abrahamsson J, Schmiegelow K, Marquart HV. 2019. Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia. Leukemia. 33(6):1324-1336. https://doi.org/10.1038/s41375-018-0307-6

MLA

Vancouver

Author

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. / Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia. I: Leukemia. 2019 ; Bind 33, Nr. 6. s. 1324-1336.

Bibtex

@article{864a99f8f0914f0cb03f449bd4c85d9e,
title = "Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic 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.",
keywords = "Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Child, Child, Preschool, Female, Flow Cytometry/methods, Follow-Up Studies, Humans, Infant, Male, Middle Aged, Neoplasm Recurrence, Local/drug therapy, Neoplasm, Residual/diagnosis, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy, Prognosis, Risk Assessment/methods, Survival Rate, Young Adult",
author = "S Modvig and Madsen, {H O} and Siitonen, {S M} and S Rosth{\o}j and A Tierens and V Juvonen and Osnes, {L T N} and H V{\aa}lerhaugen and M Hultdin and I Th{\"o}rn and R Matuzeviciene and M Stoskus and M Marincevic and L Fogelstrand and A Lilleorg and N Toft and J{\'o}nsson, {O G} and K Pruunsild and G Vaitkeviciene and K Vettenranta and B Lund and J Abrahamsson and K Schmiegelow and Marquart, {H V}",
year = "2019",
month = "6",
day = "1",
doi = "10.1038/s41375-018-0307-6",
language = "English",
volume = "33",
pages = "1324--1336",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "6",

}

RIS

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.

KW - Adolescent

KW - Adult

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Child

KW - Child, Preschool

KW - Female

KW - Flow Cytometry/methods

KW - Follow-Up Studies

KW - Humans

KW - Infant

KW - Male

KW - Middle Aged

KW - Neoplasm Recurrence, Local/drug therapy

KW - Neoplasm, Residual/diagnosis

KW - Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy

KW - Prognosis

KW - Risk Assessment/methods

KW - Survival Rate

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=85058455858&partnerID=8YFLogxK

U2 - 10.1038/s41375-018-0307-6

DO - 10.1038/s41375-018-0307-6

M3 - Journal article

VL - 33

SP - 1324

EP - 1336

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 6

ER -

ID: 56120068