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

Andrej Pešić¹Nevena Bešević¹Nicolaus Kröger²Dejana Stanisavljevic³Nada Kraguljac Kurtović⁴Zoran Bukumirić³Natalija Kecman⁴Nikola Lemajić⁴Mihailo Smiljanić⁴Nada Suvajdžić Vuković^4,5Andrija Bogdanović^4,5Ana Vidović^4,5Jelena Bila^4,5Mirjana Mitrovic^4,5Danijela Lekovic^4,5Marijana Virijević^4,5Irena Đunić^4,5Darko Antic^4,5Milena Todorović Balint^4,5*

• ¹Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia
• ²Stem Cell Transplant Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany
• ³Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
• ⁴Clinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia
• ⁵Faculty of Medicine, University of Belgrade, Belgrade, Serbia

Immune 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. Therefore, we 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. High NK cell counts on day 90 (>178/µL) were associated with improved OS (P=0.039) and lower rates of NRM (1year 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. The 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.