Abstract
The delayed recovery of adaptive immunity underlies transplant-related mortality (TRM) after αβ T cell-depleted hematopoietic stem cell transplantation (HSCT). We tested the use of low-dose memory donor lymphocyte infusions (mDLIs) after engraftment of αβ T cell-depleted grafts.
A cohort of 131 pediatric patients (median age 9 years) were grafted with αβ T cell-depleted products from either haplo (n = 79) or unrelated donors (n = 52). After engraftment, patients received mDLIs prepared by CD45RA depletion. Cell dose was escalated monthly from 25 × 103 to 100 × 103/kg (haplo) and from 100 × 103 to 300 × 103 /kg (MUD). In a subcohort of 16 patients, T-cell receptor (TCR) repertoire profiling with deep sequencing was used to track T-cell clones and to evaluate the contribution of mDLI to the immune repertoire.
In total, 343 mDLIs were administered. The cumulative incidence (CI) of grades II and III de novo acute graft-versus-host disease (aGVHD) was 5% and 2%, respectively, and the CI of chronic graft-versus-host disease was 7%. Half of the patients with undetectable CMV-specific T cells before mDLI recovered CMV-specific T cells. TCR repertoire profiling confirmed that mDLI-derived T cells significantly contribute to the TCR repertoire up to 1 year after HSCT and include persistent, CMV-specific T-cell clones.
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Acknowledgements
The authors thank the physicians and nursing staff of the HSCT Units 1 and 2 for outstanding patient care, the staff of molecular biology, microbiology, and transplant biology laboratories for excellent service. We are grateful to the “Podari Zhizn” foundation and “Science for children” foundation for continued support of the care of the patients and research in the field of HSCT.
Funding
The study was supported by RFBR grant no. 18-34-20139 (IZ, EK, FV), MM, AM, EO, DC were partly supported by grant of the Ministry of Science and Higher Education of the Russian Federation no. 075-15-2020-807.
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MM, IZ, and SB contributed equally to this work. MM designed the study, analyzed data, and wrote the paper, IZ designed the sequencing part, collected and analyzed data, and wrote the paper, SB collected and analyzed data, wrote the paper, LS collected and analyzed data, reviewed the paper, RK, DB, JS, EK, DP, YM, AK, EO, MF, SG collected and analyzed data, EK collected samples, FV sample processing, data analysis, MS bioinformatics, data analysis, DC study design, data analysis, review, GN, AM—study design, paper review.
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MM received lecturer’s fee from Miltenyi Biotec, all other authors declare no conflict of interest in relation to the current paper.
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Blagov, S., Zvyagin, I.V., Shelikhova, L. et al. T-cell tracking, safety, and effect of low-dose donor memory T-cell infusions after αβ T cell-depleted hematopoietic stem cell transplantation. Bone Marrow Transplant 56, 900–908 (2021). https://doi.org/10.1038/s41409-020-01128-2
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DOI: https://doi.org/10.1038/s41409-020-01128-2