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Analysis of donor NK and T cells infused in patients undergoing MHC-matched allogeneic hematopoietic transplantation

Abstract

We retrospectively analyzed the percentages and absolute numbers of T cells, natural killer (NK) cells and NK cell subsets in cryopreserved samples of either bone marrow or blood non-T cell-depleted allogeneic MHC-matched hematopoietic grafts. Using flow cytometry, we found higher numbers of NK cells in aphereses than in bone marrow collections. We further investigated the distribution of NK cell subsets, defined by the cell surface expression of MHC class I-specific receptors, in these allogeneic grafts. The distribution of NK cell subsets from the two different origins were similar, with the exception of the CD158a/h+ NK cell subset, whose size appeared to be smaller in bone marrow. The search for relations between the numbers of infused cells and post-transplantation events demonstrated that increasing numbers of infused T cells but not NK cells are related with decreased overall survival. Our study highlights the toxicity of infused T cells but not NK cells in allogeneic MHC-matched hematopoietic grafts. These data pave the way for further trials to investigate the effect of NK cell infusion in MHC-matched allogeneic transplantation, and in particular whether ex vivo NK cell expansion and activation may enhance the anti-tumoral effect of the procedure and decrease its morbidity.

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Acknowledgements

The authors thank Pascale Paul (CIML) for helpful discussion, the Hematology Laboratory (Hopital de la Conception) and the Cell Therapy Facility (Institut Paoli-Calmettes) for support during the conduct of this work. This work was supported in part by institutional grants from INSERM, CNRS, Ministère de l'enseignement supérieur et de la Recherche, specific grants from Ligue Nationale contre le Cancer (Equipe labellisée La Ligue), from Association pour la Recherche contre le Cancer (EV, VP) and by Institut Paoli-Calmettes. The authors also thank the Beckman-Coulter Company for its contribution to the conduct of this work.

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Pascal, V., Brunet, C., Pradel, V. et al. Analysis of donor NK and T cells infused in patients undergoing MHC-matched allogeneic hematopoietic transplantation. Leukemia 16, 2259–2266 (2002). https://doi.org/10.1038/sj.leu.2402670

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