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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.

SUBMITTER: Ando T

PROVIDER: S-EPMC6988395 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Ando Taiki T Tachibana Takayoshi T Tanaka Masatsugu M Suzuki Taisei T Ishiyama Yasufumi Y Koyama Satoshi S Ogusa Eriko E Numata Ayumi A Matsumoto Kenji K Kanamori Heiwa H Nakajima Hideaki H

Blood advances 20200101 2

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 ce ...[more]

PMID: 31990335

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Project description:T-cell receptor (TCR) ?? cells are perceived as innate-like effector cells with the possibility of mediating graft-vs. -tumor (GVT) without causing graft-vs.-host disease (GVHD) in the setting of hematopoietic allogeneic stem cell transplantation (HSCT). We conducted a prospective study to assess the clinical impact of TCR ?? cell immune reconstitution on overall survival, relapse-free-survival, relapse and GVHD. The impact of CD3, CD4, and CD8 T cells together with NK cells including subtypes were analyzed in parallel. A total of 108 patients with hematological malignancies transplanted with HLA-matched, T cell replete stem cell grafts were included for analyses of absolute concentrations of CD3, CD4, and CD8 positive T cells and NK cells together with a multi-color flow cytometry panel with staining for TCR??, TCR??, V?1, V?2, CD3, CD4, CD8, HLA-DR, CD196, CD45RO, CD45RA, CD16, CD56, CD337, and CD314 at 28, 56, 91, 180, and 365 days after transplantation. Immune reconstitution data including subsets and differentiation markers of T and NK cells during the first year after transplantation was provided. Patients with TCR ?? cell concentrations above the median value of 21 (0-416) × 106 cells/L 56 days after transplantation had significantly improved overall survival (p = 0.001) and relapse-free survival (p = 0.007) compared to patients with concentrations below this value. When day 56 cell subset concentrations were included as continuous variables, TCR ?? cells were the only T cell subsets with a significant impact on OS and RFS; the impact of TCR ?? cells remained statistically significant in multivariate analyses adjusted for pre-transplant risk factors. The risk of death from relapse was significantly decreased in patients with high concentrations of TCR ?? cells 56 days after transplantation (p = 0.003). Also, the risk of acute GVHD was significantly lower in patients with day 28 TCR ?? cell concentrations above the median of 18 × 106 cells/L compared to patients with low concentrations (p = 0.01). These results suggest a protective role of TCR ?? cells in relapse and GVHD and encourage further research in developing adaptive TCR ?? cell therapy for improving outcomes after HSCT.

Dataset Information

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

Publications

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

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