Clonal expansion of CD8+ T cells reflects graft-versus-leukemia activity and precedes durable remission following DLI

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Clonal expansion of CD8+ T cells reflects graft-versus-leukemia activity and precedes durable remission following DLI. / Schultze-Florey, Christian R; Kuhlmann, Leonie; Raha, Solaiman; Barros-Martins, Joana; Odak, Ivan; Tan, Likai; Xiao, Yankai; Ravens, Sarina; Hambach, Lothar; Venturini, Letizia; Stadler, Michael; Eder, Matthias; Thol, Felicitas; Heuser, Michael; Forster, Reinhold; Ganser, Arnold; Prinz, Immo; Koenecke, Christian.

In: BLOOD ADV, Vol. 5, No. 21, 09.11.2021, p. 4485-4499.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Schultze-Florey, CR, Kuhlmann, L, Raha, S, Barros-Martins, J, Odak, I, Tan, L, Xiao, Y, Ravens, S, Hambach, L, Venturini, L, Stadler, M, Eder, M, Thol, F, Heuser, M, Forster, R, Ganser, A, Prinz, I & Koenecke, C 2021, 'Clonal expansion of CD8+ T cells reflects graft-versus-leukemia activity and precedes durable remission following DLI', BLOOD ADV, vol. 5, no. 21, pp. 4485-4499. https://doi.org/10.1182/bloodadvances.2020004073

APA

Schultze-Florey, C. R., Kuhlmann, L., Raha, S., Barros-Martins, J., Odak, I., Tan, L., Xiao, Y., Ravens, S., Hambach, L., Venturini, L., Stadler, M., Eder, M., Thol, F., Heuser, M., Forster, R., Ganser, A., Prinz, I., & Koenecke, C. (2021). Clonal expansion of CD8+ T cells reflects graft-versus-leukemia activity and precedes durable remission following DLI. BLOOD ADV, 5(21), 4485-4499. https://doi.org/10.1182/bloodadvances.2020004073

Vancouver

Bibtex

@article{88ef1b617ce94d4394775ff666dce928,
title = "Clonal expansion of CD8+ T cells reflects graft-versus-leukemia activity and precedes durable remission following DLI",
abstract = "Donor lymphocyte infusion (DLI) is a standard of care for relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Currently it is poorly understood how and when CD8+ αβ T cells exert graft-versus-leukemia (GVL) activity after DLI. Also, there is no reliable biomarker to monitor GVL activity of the infused CD8+ T cells. Therefore, we analyzed the dynamics of CD8+ αβ T-cell clones in patients with DLI. In this prospective clinical study of 29 patients, we performed deep T-cell receptor β (TRB ) sequencing of sorted CD8+ αβ T cells to track patients' repertoire changes in response to DLI. Upon first occurrence of GVL, longitudinal analyses revealed a preferential expansion of distinct CD8+TRB clones (n = 14). This did not occur in samples of patients without signs of GVL (n = 11). Importantly, early repertoire changes 15 days after DLI predicted durable remission for the 36-month study follow-up. Furthermore, absence of clonal outgrowth of the CD8+TRB repertoire after DLI was an early biomarker that predicted relapse at a median time of 11.2 months ahead of actual diagnosis. Additionally, unbiased sample analysis regardless of the clinical outcome revealed that patients with decreasing CD8+TRB diversity at day 15 after DLI (n = 13) had a lower relapse incidence (P = .0040) compared with patients without clonal expansion (n = 6). In conclusion, CD8+TRB analysis may provide a reliable tool for predicting the efficacy of DLI and holds the potential to identify patients at risk for progression and relapse after DLI.",
author = "Schultze-Florey, {Christian R} and Leonie Kuhlmann and Solaiman Raha and Joana Barros-Martins and Ivan Odak and Likai Tan and Yankai Xiao and Sarina Ravens and Lothar Hambach and Letizia Venturini and Michael Stadler and Matthias Eder and Felicitas Thol and Michael Heuser and Reinhold Forster and Arnold Ganser and Immo Prinz and Christian Koenecke",
note = "Copyright {\textcopyright} 2021 American Society of Hematology.",
year = "2021",
month = nov,
day = "9",
doi = "10.1182/bloodadvances.2020004073",
language = "English",
volume = "5",
pages = "4485--4499",
journal = "BLOOD ADV",
issn = "2473-9529",
publisher = "Elsevier BV",
number = "21",

}

RIS

TY - JOUR

T1 - Clonal expansion of CD8+ T cells reflects graft-versus-leukemia activity and precedes durable remission following DLI

AU - Schultze-Florey, Christian R

AU - Kuhlmann, Leonie

AU - Raha, Solaiman

AU - Barros-Martins, Joana

AU - Odak, Ivan

AU - Tan, Likai

AU - Xiao, Yankai

AU - Ravens, Sarina

AU - Hambach, Lothar

AU - Venturini, Letizia

AU - Stadler, Michael

AU - Eder, Matthias

AU - Thol, Felicitas

AU - Heuser, Michael

AU - Forster, Reinhold

AU - Ganser, Arnold

AU - Prinz, Immo

AU - Koenecke, Christian

N1 - Copyright © 2021 American Society of Hematology.

PY - 2021/11/9

Y1 - 2021/11/9

N2 - Donor lymphocyte infusion (DLI) is a standard of care for relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Currently it is poorly understood how and when CD8+ αβ T cells exert graft-versus-leukemia (GVL) activity after DLI. Also, there is no reliable biomarker to monitor GVL activity of the infused CD8+ T cells. Therefore, we analyzed the dynamics of CD8+ αβ T-cell clones in patients with DLI. In this prospective clinical study of 29 patients, we performed deep T-cell receptor β (TRB ) sequencing of sorted CD8+ αβ T cells to track patients' repertoire changes in response to DLI. Upon first occurrence of GVL, longitudinal analyses revealed a preferential expansion of distinct CD8+TRB clones (n = 14). This did not occur in samples of patients without signs of GVL (n = 11). Importantly, early repertoire changes 15 days after DLI predicted durable remission for the 36-month study follow-up. Furthermore, absence of clonal outgrowth of the CD8+TRB repertoire after DLI was an early biomarker that predicted relapse at a median time of 11.2 months ahead of actual diagnosis. Additionally, unbiased sample analysis regardless of the clinical outcome revealed that patients with decreasing CD8+TRB diversity at day 15 after DLI (n = 13) had a lower relapse incidence (P = .0040) compared with patients without clonal expansion (n = 6). In conclusion, CD8+TRB analysis may provide a reliable tool for predicting the efficacy of DLI and holds the potential to identify patients at risk for progression and relapse after DLI.

AB - Donor lymphocyte infusion (DLI) is a standard of care for relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Currently it is poorly understood how and when CD8+ αβ T cells exert graft-versus-leukemia (GVL) activity after DLI. Also, there is no reliable biomarker to monitor GVL activity of the infused CD8+ T cells. Therefore, we analyzed the dynamics of CD8+ αβ T-cell clones in patients with DLI. In this prospective clinical study of 29 patients, we performed deep T-cell receptor β (TRB ) sequencing of sorted CD8+ αβ T cells to track patients' repertoire changes in response to DLI. Upon first occurrence of GVL, longitudinal analyses revealed a preferential expansion of distinct CD8+TRB clones (n = 14). This did not occur in samples of patients without signs of GVL (n = 11). Importantly, early repertoire changes 15 days after DLI predicted durable remission for the 36-month study follow-up. Furthermore, absence of clonal outgrowth of the CD8+TRB repertoire after DLI was an early biomarker that predicted relapse at a median time of 11.2 months ahead of actual diagnosis. Additionally, unbiased sample analysis regardless of the clinical outcome revealed that patients with decreasing CD8+TRB diversity at day 15 after DLI (n = 13) had a lower relapse incidence (P = .0040) compared with patients without clonal expansion (n = 6). In conclusion, CD8+TRB analysis may provide a reliable tool for predicting the efficacy of DLI and holds the potential to identify patients at risk for progression and relapse after DLI.

U2 - 10.1182/bloodadvances.2020004073

DO - 10.1182/bloodadvances.2020004073

M3 - SCORING: Journal article

C2 - 34535011

VL - 5

SP - 4485

EP - 4499

JO - BLOOD ADV

JF - BLOOD ADV

SN - 2473-9529

IS - 21

ER -