Navigating preemptive and therapeutic donor lymphocyte infusions in advanced myeloid malignancies by high-sensitivity chimerism analysis
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Navigating preemptive and therapeutic donor lymphocyte infusions in advanced myeloid malignancies by high-sensitivity chimerism analysis. / Stadler, Michael; Venturini, Letizia; Bünting, Ivonne; Dammann, Elke; Weissinger, Eva M; Schwarzer, Adrian; Schultze-Florey, Christian; Ehrlich, Steve; Markel, Dominik; Lueck, Catherina; Gladysz, Alexandra; Fröhlich, Tabea; Damrah, Nouraldin; Beutel, Gernot; Eder, Matthias; Ganser, Arnold; Hambach, Lothar.
in: FRONT ONCOL, Jahrgang 12, 2022, S. 867356.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › Kurzpublikation › Forschung › Begutachtung
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TY - JOUR
T1 - Navigating preemptive and therapeutic donor lymphocyte infusions in advanced myeloid malignancies by high-sensitivity chimerism analysis
AU - Stadler, Michael
AU - Venturini, Letizia
AU - Bünting, Ivonne
AU - Dammann, Elke
AU - Weissinger, Eva M
AU - Schwarzer, Adrian
AU - Schultze-Florey, Christian
AU - Ehrlich, Steve
AU - Markel, Dominik
AU - Lueck, Catherina
AU - Gladysz, Alexandra
AU - Fröhlich, Tabea
AU - Damrah, Nouraldin
AU - Beutel, Gernot
AU - Eder, Matthias
AU - Ganser, Arnold
AU - Hambach, Lothar
N1 - Copyright © 2022 Stadler, Venturini, Bünting, Dammann, Weissinger, Schwarzer, Schultze-Florey, Ehrlich, Markel, Lueck, Gladysz, Fröhlich, Damrah, Beutel, Eder, Ganser and Hambach.
PY - 2022
Y1 - 2022
N2 - Preemptive and therapeutic donor lymphocyte infusions (preDLI and tDLI) are widely used in relapsing and relapsed hematopoietic malignancies after allogeneic stem cell transplantation (alloSCT) to enhance the graft-versus-malignancy effect. However, in advanced myeloid malignancies, long-term survival after preDLI and tDLI remains low, reflecting our inability to master the double-edged sword of alloreactivity, balancing anti-neoplastic activity versus graft-versus-host disease (GvHD). We previously evaluated a quantitative PCR-based high-sensitivity chimerism (hs-chimerism) based on insertion/deletion polymorphisms instead of short tandem repeats, where increasing host chimerism in peripheral blood predicts relapse more than a month before clinical diagnosis, and declining host chimerism signals anti-host alloreactivity. Here we report 32 consecutive patients with advanced myeloid malignancies receiving preDLI or tDLI "navigated" by hs-chimerism ("navigated DLI"). We compared them to a historical cohort of 110 consecutive preDLI or tDLI recipients, prior to implementation of hs-chimerism at our institution ("controls"). Both groups were comparable regarding age, gender, conditioning, donor type, and time to DLI. With longer median follow-up of the navigated DLI group (8.5 versus 5 months), their landmark overall (64%) and disease-free survival (62%) at 2 years from first DLI compared favorably with controls (23% and 21%, respectively). Improved survival of navigated DLI was due to both reduced relapse incidence (38% versus 60%) and non-relapse mortality (17% versus 44%) at 2 years. Early relapse prediction by hs-chimerism allowed a preemptive approach in 28% of navigated DLI versus 7% in controls. Our results confirm hs-chimerism as a highly valuable tool for monitoring and steering immune interventions after alloSCT.
AB - Preemptive and therapeutic donor lymphocyte infusions (preDLI and tDLI) are widely used in relapsing and relapsed hematopoietic malignancies after allogeneic stem cell transplantation (alloSCT) to enhance the graft-versus-malignancy effect. However, in advanced myeloid malignancies, long-term survival after preDLI and tDLI remains low, reflecting our inability to master the double-edged sword of alloreactivity, balancing anti-neoplastic activity versus graft-versus-host disease (GvHD). We previously evaluated a quantitative PCR-based high-sensitivity chimerism (hs-chimerism) based on insertion/deletion polymorphisms instead of short tandem repeats, where increasing host chimerism in peripheral blood predicts relapse more than a month before clinical diagnosis, and declining host chimerism signals anti-host alloreactivity. Here we report 32 consecutive patients with advanced myeloid malignancies receiving preDLI or tDLI "navigated" by hs-chimerism ("navigated DLI"). We compared them to a historical cohort of 110 consecutive preDLI or tDLI recipients, prior to implementation of hs-chimerism at our institution ("controls"). Both groups were comparable regarding age, gender, conditioning, donor type, and time to DLI. With longer median follow-up of the navigated DLI group (8.5 versus 5 months), their landmark overall (64%) and disease-free survival (62%) at 2 years from first DLI compared favorably with controls (23% and 21%, respectively). Improved survival of navigated DLI was due to both reduced relapse incidence (38% versus 60%) and non-relapse mortality (17% versus 44%) at 2 years. Early relapse prediction by hs-chimerism allowed a preemptive approach in 28% of navigated DLI versus 7% in controls. Our results confirm hs-chimerism as a highly valuable tool for monitoring and steering immune interventions after alloSCT.
U2 - 10.3389/fonc.2022.867356
DO - 10.3389/fonc.2022.867356
M3 - Short publication
C2 - 36059667
VL - 12
SP - 867356
JO - FRONT ONCOL
JF - FRONT ONCOL
SN - 2234-943X
ER -
