1. Selected memory T cells infused post haploidentical hematopoietic stem cell transplantation persist and hyper-expand
- Author
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Jasper J. P. van Beek, Simone Puccio, Clara Di Vito, Federica De Paoli, Elisa Zaghi, Michela Calvi, Alice Scarpa, Clelia Peano, Gianluca Basso, Javier Cibella, Chiara De Philippis, Barbara Sarina, Inna Timofeeva, Rossana Capizzuto, Daniele Mannina, Rossana Mineri, Jacopo Mariotti, Roberto Crocchiolo, Armando Santoro, Luca Castagna, Stefania Bramanti, Domenico Mavilio, and Enrico Lugli
- Subjects
Hematology - Abstract
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide is a curative treatment for many hematological malignancies, yet a majority of patients still suffers from recurrent infections. Post-transplant infusion of memory T cells could potentially enhance immunological protection without increasing the risk of eliciting acute graft-versus-host disease, which is mainly induced by naïve T cells. Here, we performed longitudinal analysis of the lymphocyte compartment in 19 haplo-HSCT patients previously enrolled in a phase II prospective clinical trial (ClinicalTrials.gov Identifier: NCT04687982), in which they received post-transplant CD45RA-depleted donor lymphocyte infusions (DLI). T cell receptor sequencing analysis showed that, surprisingly, CD45RA-depleted DLI do not increase T cell clonal diversity, but lead to prominent expansion of a selected number of infused memory T cell clones, suggestive of recruitment of these cells in the immune response. Pathogen-specific memory T cells, including cytomegalovirus (CMV)-specific cells, engrafted and were able to persist for at least one month. Deep immunophenotyping revealed strong polyfunctional effector CMV-specific T cell responses in the majority of patients, with their expansion correlating with the frequency of CMV-specific cells in the donor. These findings provide a rationale behind the suggested improved protection against viral infections for patients receiving CD45RA-depleted DLI.
- Published
- 2022
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