High NK cell counts at day 90 predict improved survival in event-free patients after T-cell depleted allogeneic stem cell transplantation

IntroductionImmune reconstitution (IR) after allogeneic stem cell transplantation has been highlighted as pivotal in achieving favorable long-term outcomes by influencing the rates of infection, graft versus host disease (GvHD) and relapse. However, data on the impact of different lymphocyte subsets...

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Main Authors: Andrej Pešić, Nevena Bešević, Nicolaus Kröger, Dejana Stanisavljević, Nada Kraguljac Kurtović, Zoran Bukumirić, Natalija Kecman, Nikola Lemajić, Mihailo Smiljanić, Nada Suvajdžić Vuković, Andrija Bogdanović, Ana Vidović, Jelena Bila, Mirjana Mitrović, Danijela Leković, Marijana Virijević, Irena Đunić, Darko Antić, Milena Todorović Balint
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1577924/full
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author Andrej Pešić
Nevena Bešević
Nicolaus Kröger
Dejana Stanisavljević
Dejana Stanisavljević
Nada Kraguljac Kurtović
Zoran Bukumirić
Zoran Bukumirić
Natalija Kecman
Nikola Lemajić
Mihailo Smiljanić
Nada Suvajdžić Vuković
Nada Suvajdžić Vuković
Andrija Bogdanović
Andrija Bogdanović
Ana Vidović
Ana Vidović
Jelena Bila
Jelena Bila
Mirjana Mitrović
Mirjana Mitrović
Danijela Leković
Danijela Leković
Marijana Virijević
Marijana Virijević
Irena Đunić
Irena Đunić
Darko Antić
Darko Antić
Milena Todorović Balint
Milena Todorović Balint
author_facet Andrej Pešić
Nevena Bešević
Nicolaus Kröger
Dejana Stanisavljević
Dejana Stanisavljević
Nada Kraguljac Kurtović
Zoran Bukumirić
Zoran Bukumirić
Natalija Kecman
Nikola Lemajić
Mihailo Smiljanić
Nada Suvajdžić Vuković
Nada Suvajdžić Vuković
Andrija Bogdanović
Andrija Bogdanović
Ana Vidović
Ana Vidović
Jelena Bila
Jelena Bila
Mirjana Mitrović
Mirjana Mitrović
Danijela Leković
Danijela Leković
Marijana Virijević
Marijana Virijević
Irena Đunić
Irena Đunić
Darko Antić
Darko Antić
Milena Todorović Balint
Milena Todorović Balint
author_sort Andrej Pešić
collection DOAJ
description IntroductionImmune reconstitution (IR) after allogeneic stem cell transplantation has been highlighted as pivotal in achieving favorable long-term outcomes by influencing the rates of infection, graft versus host disease (GvHD) and relapse. However, data on the impact of different lymphocyte subsets influencing outcomes is conflicting. Furthermore, the importance of immune reconstitution parameters in patients previously not experiencing major post-transplant complications is lacking.MethodsWe evaluated the clinical impact of day 90 NK cell, CD4+ T-cell, CD8+ T-cell, B-cell, and NKT cell counts on transplant outcomes by performing a landmark analysis in event-free patients. Lymphocyte subset counts were obtained from 70 patients undergoing in vivo T-cell depleted allogeneic transplantation from 2018 to 2024. Patients eligible for the study experienced no acute GvHD, poor graft function, graft failure, or relapse in the first three months after transplantation-prior to obtaining IR data. We associated lymphocyte subset counts to overall survival (OS), non-relapse mortality (NRM), cumulative incidence of relapse (RI), and secondary graft failure/poor graft function.ResultsHigh NK cell counts on day 90 (>178/μL) were associated with improved OS (P=0.039) and lower rates of NRM (1-year cumulative incidence of 5.7% versus 31.4%, HR 0.16, 95% CI 0.04-0.69, P=0.014). A protective effect on RI was not found. We found no patient, disease or transplant-related variables to be significantly associated with day 90 NK cell counts.ConclusionThe results suggest that high NK cell counts on day 90 after T-cell depleted allogeneic transplantation independently protect from NRM and improve OS in patients without prior major post-transplant complications.
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spelling doaj-art-5a59f17bf3be4c72a8ce2bc5190fa9682025-08-20T02:07:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15779241577924High NK cell counts at day 90 predict improved survival in event-free patients after T-cell depleted allogeneic stem cell transplantationAndrej Pešić0Nevena Bešević1Nicolaus Kröger2Dejana Stanisavljević3Dejana Stanisavljević4Nada Kraguljac Kurtović5Zoran Bukumirić6Zoran Bukumirić7Natalija Kecman8Nikola Lemajić9Mihailo Smiljanić10Nada Suvajdžić Vuković11Nada Suvajdžić Vuković12Andrija Bogdanović13Andrija Bogdanović14Ana Vidović15Ana Vidović16Jelena Bila17Jelena Bila18Mirjana Mitrović19Mirjana Mitrović20Danijela Leković21Danijela Leković22Marijana Virijević23Marijana Virijević24Irena Đunić25Irena Đunić26Darko Antić27Darko Antić28Milena Todorović Balint29Milena Todorović Balint30Clinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaDepartment of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyFaculty of Medicine, University of Belgrade, Belgrade, SerbiaInstitute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Belgrade, SerbiaInstitute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Belgrade, SerbiaClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Belgrade, SerbiaIntroductionImmune reconstitution (IR) after allogeneic stem cell transplantation has been highlighted as pivotal in achieving favorable long-term outcomes by influencing the rates of infection, graft versus host disease (GvHD) and relapse. However, data on the impact of different lymphocyte subsets influencing outcomes is conflicting. Furthermore, the importance of immune reconstitution parameters in patients previously not experiencing major post-transplant complications is lacking.MethodsWe evaluated the clinical impact of day 90 NK cell, CD4+ T-cell, CD8+ T-cell, B-cell, and NKT cell counts on transplant outcomes by performing a landmark analysis in event-free patients. Lymphocyte subset counts were obtained from 70 patients undergoing in vivo T-cell depleted allogeneic transplantation from 2018 to 2024. Patients eligible for the study experienced no acute GvHD, poor graft function, graft failure, or relapse in the first three months after transplantation-prior to obtaining IR data. We associated lymphocyte subset counts to overall survival (OS), non-relapse mortality (NRM), cumulative incidence of relapse (RI), and secondary graft failure/poor graft function.ResultsHigh NK cell counts on day 90 (>178/μL) were associated with improved OS (P=0.039) and lower rates of NRM (1-year cumulative incidence of 5.7% versus 31.4%, HR 0.16, 95% CI 0.04-0.69, P=0.014). A protective effect on RI was not found. We found no patient, disease or transplant-related variables to be significantly associated with day 90 NK cell counts.ConclusionThe results suggest that high NK cell counts on day 90 after T-cell depleted allogeneic transplantation independently protect from NRM and improve OS in patients without prior major post-transplant complications.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1577924/fullNK cellsallogeneic stem cell transplantationimmune reconstitutionT-cell depleted grafttransplant outcomes
spellingShingle Andrej Pešić
Nevena Bešević
Nicolaus Kröger
Dejana Stanisavljević
Dejana Stanisavljević
Nada Kraguljac Kurtović
Zoran Bukumirić
Zoran Bukumirić
Natalija Kecman
Nikola Lemajić
Mihailo Smiljanić
Nada Suvajdžić Vuković
Nada Suvajdžić Vuković
Andrija Bogdanović
Andrija Bogdanović
Ana Vidović
Ana Vidović
Jelena Bila
Jelena Bila
Mirjana Mitrović
Mirjana Mitrović
Danijela Leković
Danijela Leković
Marijana Virijević
Marijana Virijević
Irena Đunić
Irena Đunić
Darko Antić
Darko Antić
Milena Todorović Balint
Milena Todorović Balint
High NK cell counts at day 90 predict improved survival in event-free patients after T-cell depleted allogeneic stem cell transplantation
Frontiers in Immunology
NK cells
allogeneic stem cell transplantation
immune reconstitution
T-cell depleted graft
transplant outcomes
title High NK cell counts at day 90 predict improved survival in event-free patients after T-cell depleted allogeneic stem cell transplantation
title_full High NK cell counts at day 90 predict improved survival in event-free patients after T-cell depleted allogeneic stem cell transplantation
title_fullStr High NK cell counts at day 90 predict improved survival in event-free patients after T-cell depleted allogeneic stem cell transplantation
title_full_unstemmed High NK cell counts at day 90 predict improved survival in event-free patients after T-cell depleted allogeneic stem cell transplantation
title_short High NK cell counts at day 90 predict improved survival in event-free patients after T-cell depleted allogeneic stem cell transplantation
title_sort high nk cell counts at day 90 predict improved survival in event free patients after t cell depleted allogeneic stem cell transplantation
topic NK cells
allogeneic stem cell transplantation
immune reconstitution
T-cell depleted graft
transplant outcomes
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1577924/full
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