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 journal › SCORING: Journal article › Research › peer-review
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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 -
