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Improved Relapse-Free Survival in Patients With High Natural Killer Cell Doses in Grafts and During Early Immune Reconstitution After Allogeneic Stem Cell Transplantation

Mature immunocompetent cells from the stem cell graft as well as early robust immune reconstitution are essential for the graft-vs. -tumor (GVT) effect to eliminate residual malignant cells after allogeneic hematopoietic stem cell transplantation (HSCT). In this prospective study we characterized gr...

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Autores principales: Minculescu, Lia, Fischer-Nielsen, Anne, Haastrup, Eva, Ryder, Lars Peter, Andersen, Niels Smedegaard, Schjoedt, Ida, Friis, Lone Smidstrup, Kornblit, Brian Thomas, Petersen, Søren Lykke, Sengelov, Henrik, Marquart, Hanne Vibeke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273963/
https://www.ncbi.nlm.nih.gov/pubmed/32547559
http://dx.doi.org/10.3389/fimmu.2020.01068
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author Minculescu, Lia
Fischer-Nielsen, Anne
Haastrup, Eva
Ryder, Lars Peter
Andersen, Niels Smedegaard
Schjoedt, Ida
Friis, Lone Smidstrup
Kornblit, Brian Thomas
Petersen, Søren Lykke
Sengelov, Henrik
Marquart, Hanne Vibeke
author_facet Minculescu, Lia
Fischer-Nielsen, Anne
Haastrup, Eva
Ryder, Lars Peter
Andersen, Niels Smedegaard
Schjoedt, Ida
Friis, Lone Smidstrup
Kornblit, Brian Thomas
Petersen, Søren Lykke
Sengelov, Henrik
Marquart, Hanne Vibeke
author_sort Minculescu, Lia
collection PubMed
description Mature immunocompetent cells from the stem cell graft as well as early robust immune reconstitution are essential for the graft-vs. -tumor (GVT) effect to eliminate residual malignant cells after allogeneic hematopoietic stem cell transplantation (HSCT). In this prospective study we characterized graft composition of T- and NK cell subsets in 88 recipients of peripheral blood stem cell grafts with multicolor flowcytometry. Our primary aim was to analyze the impact of graft composition on immune reconstitution and clinical outcomes after transplantation. Patients transplanted with graft NK cell doses above the median value of 27 × 10(6)/kg had significantly increased relapse-free-survival compared to patients transplanted with lower doses, HR 2.12 (95% CI 1.01–4.45, p = 0.04) Peripheral blood concentrations of NK cells obtained from donors before G-CSF mobilization were significantly correlated to graft NK cell doses (Spearman's ρ 0.53, p = 0.03). The dose of transplanted NK cells/kg correlated significantly with NK cell concentrations in patients early after transplantation (Spearman's ρ 0.26, p = 0.02, and ρ = 0.35, p = 0.001 for days 28 and 56, respectively). Early immune reconstitution above median values of NK cells was significantly associated with improved relapse-free survival (HR 2.84 [95% CI 1.29–6.28], p = 0.01, and HR 4.19 [95% CI 1.68–10.4], p = 0.002, for day 28 and 56, respectively). Early concentrations above the median value of the mature effector CD56dim NK cell subset were significantly associated with decreased relapse incidences at 1 year, 7% (95% CI 1.8–17) vs. 28% (95% CI 15–42), p = 0.04, and 7% (95% CI 1.8–18) vs. 26% (95% CI 14–40) %, p = 0.03, for days 28 and 56, respectively. The results suggest a protective effect of high doses of NK cells in grafts and during early immune reconstitution and support the perception of NK cells as innate effector cells with anti-tumor effects in the setting of allogeneic stem cell transplantation.
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spelling pubmed-72739632020-06-15 Improved Relapse-Free Survival in Patients With High Natural Killer Cell Doses in Grafts and During Early Immune Reconstitution After Allogeneic Stem Cell Transplantation Minculescu, Lia Fischer-Nielsen, Anne Haastrup, Eva Ryder, Lars Peter Andersen, Niels Smedegaard Schjoedt, Ida Friis, Lone Smidstrup Kornblit, Brian Thomas Petersen, Søren Lykke Sengelov, Henrik Marquart, Hanne Vibeke Front Immunol Immunology Mature immunocompetent cells from the stem cell graft as well as early robust immune reconstitution are essential for the graft-vs. -tumor (GVT) effect to eliminate residual malignant cells after allogeneic hematopoietic stem cell transplantation (HSCT). In this prospective study we characterized graft composition of T- and NK cell subsets in 88 recipients of peripheral blood stem cell grafts with multicolor flowcytometry. Our primary aim was to analyze the impact of graft composition on immune reconstitution and clinical outcomes after transplantation. Patients transplanted with graft NK cell doses above the median value of 27 × 10(6)/kg had significantly increased relapse-free-survival compared to patients transplanted with lower doses, HR 2.12 (95% CI 1.01–4.45, p = 0.04) Peripheral blood concentrations of NK cells obtained from donors before G-CSF mobilization were significantly correlated to graft NK cell doses (Spearman's ρ 0.53, p = 0.03). The dose of transplanted NK cells/kg correlated significantly with NK cell concentrations in patients early after transplantation (Spearman's ρ 0.26, p = 0.02, and ρ = 0.35, p = 0.001 for days 28 and 56, respectively). Early immune reconstitution above median values of NK cells was significantly associated with improved relapse-free survival (HR 2.84 [95% CI 1.29–6.28], p = 0.01, and HR 4.19 [95% CI 1.68–10.4], p = 0.002, for day 28 and 56, respectively). Early concentrations above the median value of the mature effector CD56dim NK cell subset were significantly associated with decreased relapse incidences at 1 year, 7% (95% CI 1.8–17) vs. 28% (95% CI 15–42), p = 0.04, and 7% (95% CI 1.8–18) vs. 26% (95% CI 14–40) %, p = 0.03, for days 28 and 56, respectively. The results suggest a protective effect of high doses of NK cells in grafts and during early immune reconstitution and support the perception of NK cells as innate effector cells with anti-tumor effects in the setting of allogeneic stem cell transplantation. Frontiers Media S.A. 2020-05-29 /pmc/articles/PMC7273963/ /pubmed/32547559 http://dx.doi.org/10.3389/fimmu.2020.01068 Text en Copyright © 2020 Minculescu, Fischer-Nielsen, Haastrup, Ryder, Andersen, Schjoedt, Friis, Kornblit, Petersen, Sengelov and Marquart. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Minculescu, Lia
Fischer-Nielsen, Anne
Haastrup, Eva
Ryder, Lars Peter
Andersen, Niels Smedegaard
Schjoedt, Ida
Friis, Lone Smidstrup
Kornblit, Brian Thomas
Petersen, Søren Lykke
Sengelov, Henrik
Marquart, Hanne Vibeke
Improved Relapse-Free Survival in Patients With High Natural Killer Cell Doses in Grafts and During Early Immune Reconstitution After Allogeneic Stem Cell Transplantation
title Improved Relapse-Free Survival in Patients With High Natural Killer Cell Doses in Grafts and During Early Immune Reconstitution After Allogeneic Stem Cell Transplantation
title_full Improved Relapse-Free Survival in Patients With High Natural Killer Cell Doses in Grafts and During Early Immune Reconstitution After Allogeneic Stem Cell Transplantation
title_fullStr Improved Relapse-Free Survival in Patients With High Natural Killer Cell Doses in Grafts and During Early Immune Reconstitution After Allogeneic Stem Cell Transplantation
title_full_unstemmed Improved Relapse-Free Survival in Patients With High Natural Killer Cell Doses in Grafts and During Early Immune Reconstitution After Allogeneic Stem Cell Transplantation
title_short Improved Relapse-Free Survival in Patients With High Natural Killer Cell Doses in Grafts and During Early Immune Reconstitution After Allogeneic Stem Cell Transplantation
title_sort improved relapse-free survival in patients with high natural killer cell doses in grafts and during early immune reconstitution after allogeneic stem cell transplantation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273963/
https://www.ncbi.nlm.nih.gov/pubmed/32547559
http://dx.doi.org/10.3389/fimmu.2020.01068
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