Impact of graft sources on immune reconstitution and survival outcomes following allogeneic stem cell transplantation

Abstract

We evaluated the kinetics of immune reconstitution (IR) after allogeneic hematopoietic cell transplantation (HSCT) and analyzed the clinical effect of IR on posttransplant outcomes. Absolute lymphocyte and its subset counts were measured using flow cytometry on days 28, 100, 180, 365, and 730 after transplantation in 358 adult patients who underwent HSCT between 2009 and 2017. On day 100 after HSCT, 310 surviving patients were analyzed. Bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), and cord blood transplantation (CBT) were performed in 119, 55, and 136 patients, respectively. Mature B-cell and differentiated natural killer (NK) cell subset counts significantly increased after CBT. The 2-year overall survival (OS), nonrelapse mortality (NRM), cumulative incidence of relapse, and chronic GVHD in BMT, PBSCT, and CBT were 62%, 67%, and 76% (P = .021); 17%, 17%, and 13% (P = .82); 33%, 40%, and 27% (P = .063); and 43%, 45%, and 28% (P = .025), respectively. Multivariate analysis showed that higher CD16+CD57− NK cell counts correlated with lower disease relapse, whereas higher CD20+ B-cell counts correlated with lower NRM. OS-favoring factors were higher CD16+CD57− NK cell count (hazard ratio, 0.36; 95% confidence interval, 0.22-0.60; P < .001) and CD20+ B-cell count (hazard ratio, 0.53; 95% confidence interval, 0.30-0.93; P < .001) and lower Disease Risk/HCT-Specific Comorbidity index score. Collective contribution of graft source-specific and event-related immune reconstitution might yield better posttransplant outcomes in CBT.

Associations between the Gut Microbiota, Immune Reconstitution, and Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation

“…Enhanced neutrophil recovery provides innate immune defense against bacterial and fungal infections and can shorten hospital stay, yet has been associated with a risk of potentiating GvHD [12]. Likewise, increased natural killer (NK) cell recovery at days 28 and 56 decreases the risk of relapse, but may come at the expense of increased risk of GVHD [13,14]. Although early monocyte recovery is associated with decreased risk of relapse and improved overall survival, [15][16][17] early recovery of immune regulatory myeloid derived-suppressor cells at day 14 increases the risk of both relapse and paradoxically severe acute GVHD [18].…”

“…2021;3(1):e210004. https://doi.org/10.20900/immunometab20210004 Immunometabolism 3 of 20 relapse mortality [14,29]. Thus, the kinetics of reconstitution of numerous distinct immune subsets contribute to the outcomes of allo-HSCT.…”

“…Protects against opportunistic infection [30] Early recovery associated with increased risk of GVHD [30] Monocyte Early recovery associated with less relapse in certain subsets [31] Timing of recovery not clearly associated with aGVHD [15] Dendritic cell Low plasmacytoid dendritic cell recovery associated with relapse and infection [32] High plasmacytoid and myeloid dendritic cell recovery associated with less incidence of severe aGVHD [32,33] NK cell Early recovery associated with less relapse [13,14] Early recovery associated with increased risk of aGVHD [13,14] Immunometabolism. 2021;3(1):e210004.…”

“…Early recovery associated with less infection [14,29] Early recovery associated with decreased risk of aGVHD [29] Abbreviations: aGVHD, acute graft versus host disease; NK, natural killer; Th, T helper cell; Treg, T regulatory cell.…”

Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

“…4 After the engraftment, the donor-derived immune system undergoes a reconstitution phase consisting of a progressive acquisition of competences that relies on the recovery of innate immunity cells during the first weeks, and of adaptive immune cells in the subsequent months. 3,[5][6][7] Neutrophils are therefore among the first cells to reconstitute, accounting for almost all peripheral blood cells in the first weeks after alloHSCT. 3 The other cells present during this period are monocytes, natural killer (NK) cells, dendritic cells (DCs), and residual T cells infused with the graft product and undergoing peripheral expansion 3,7 .…”