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. 2023 Jul 19:16:2993-3008.
doi: 10.2147/JIR.S416708. eCollection 2023.

Impact of Early Natural Killer Cell Reconstitution on the Outcomes of T Cell-Replete Allogeneic Hematopoietic Stem Cell Transplantation

Ziwei Zhou  1 , Xuan Liu  1 , Xuejun Zhang  1 , Shupeng Wen  1 , Huan Hua  1 , Zhenzhen Wang  1 , Zheng Xu  1 , Yu Lu  1 , Fuxu Wang  1
Affiliations

Impact of Early Natural Killer Cell Reconstitution on the Outcomes of T Cell-Replete Allogeneic Hematopoietic Stem Cell Transplantation

Ziwei Zhou et al. J Inflamm Res. .

Abstract

Background: Early immune reconstitution is crucial to successful outcomes after allogeneic stem cell transplantation (allo-HSCT). However, in T cell-replete HSCT, the impact of natural killer (NK) cells on transplantation outcome and the factors influencing early NK cell reconstitution remain unclear.

Methods: In this retrospective study, we analyzed 128 patients with hematological malignancies who received the first T cell-replete allo-HSCT between May 2019 and September 2021. After application of a conditioning regimen, prophylaxis for graft versus host disease (GVHD), and engraftment, the patients received prevention and treatment procedures for cytomegalovirus (CMV) reactivation. NK cells, T lymphocytes and B lymphocytes in peripheral blood were collected and analyzed at 30, 60, 90, 135 and 180 days after transplantation to observe immune cell reconstitution. Overall survival (OS), relapse-free survival (RFS), minimal residual disease (MRD), relapse, and non-relapse mortality (NRM) were evaluated. SPSS 25.0 and R version 4.2.1 were used for statistical analysis.

Results: In patients with rapid NK recovery (NK cell count at 30 days post-HSCT [NK30] >165/μL and 60 days post-HSCT [NK60] >265/μL), we observed lower rates of NRM, CMV reactivation and acute GVHD (aGVHD). Multivariate analysis indicated that a lower NK30 (≤165/μL) was an independent factor associated with inferior OS and RFS. The NK30 and NK60 in patients with CMV reactivation and aGVHD after transplantation were significantly lower than those in patients without these complications. In addition, CD107a expression in NK cells was also significantly lower in patients who experienced aGVHD. Correlation analysis did not find an inhibitory effect of T-lymphocyte subset reconstitution on NK cells in the early stage after transplantation.

Conclusion: Rapid NK cell reconstitution early after allo-HSCT had protective effects on NRM and survival. Promoting early NK cell reconstitution represents a new approach to improving the outcomes of allo-HSCT.

Keywords: T-cell replete; allogeneic hematopoietic stem cell transplantation; immune reconstitution; natural killer cells; non-relapse mortality.

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Conflict of interest statement

We declare that we have no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of patient inclusion.
Figure 2
Figure 2
ROC curve for NK30 as a predictor of all-cause mortality.
Figure 3
Figure 3
Relapse according to NK cell reconstitution after HSCT. (A) Cumulative incidence of relapse in patients with high versus low NK30. (B) Cumulative incidence of relapse in patients with high versus low NK60.
Figure 4
Figure 4
NRM according to NK cell reconstitution after HSCT. (A) Cumulative incidence of NRM in patients with high versus low NK30. (B) Cumulative incidence of NRM in patients with high versus low NK60.
Figure 5
Figure 5
OS and RFS according to NK cell reconstitution after HSCT. (A) OS among patients with high versus low NK30. (B) OS among patients with high versus low NK60. (C) RFS among patients with high versus low NK30. (D) RFS among patients with high versus low NK60.
Figure 6
Figure 6
CMV reactivation according to NK cell reconstitution after HSCT. (A) Cumulative incidence of CMV reactivation in patients with high versus low NK30. (B) Cumulative incidence of CMV reactivation in patients with high versus low NK60, (C) NK cell counts in patients with CMV reactivation and without reactivation (mean±standard deviation). (D) CD107a expression level in NK cells in patients with CMV reactivation and without (nonreactivation) (mean±standard deviation).
Figure 7
Figure 7
aGVHD according to NK cell reconstitution after HSCT. (A) Cumulative incidence of aGVHD in patients with high versus low NK30. (B). Cumulative incidence of aGVHD in patients with high versus low NK60. (C) NK cell count in patients with and without aGVHD (mean±standard deviation). (D) CD107a expression level in NK cells in patients with and without aGVHD (mean±standard deviation).
Figure 8
Figure 8
Correlations among numbers of reconstituted NK cells and T cells after HSCT. (A–C): Linear correlation analysis of NK30 and counts for T-cell subsets at 30 days post-HSCT. (D–F): Linear correlation analysis of NK60 and counts for T-cell subsets at 60 days post-HSCT.
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