Time series clustering of T cell subsets dissects heterogeneity in immune reconstitution and clinical outcomes among MUD-HCT patients receiving ATG or PTCy.

Introduction: Anti-T-lymphocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy) prevent graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT), yet individual patients benefit differentially.

Methods: Given the sparse comparative data on the impact of cellular immune reconstitution in this setting, we studied flow cytometry and clinical outcomes in 339 recipients of 10/10 matched-unrelated donor (MUD) HCT using either ATG (n=304) or PTCy (n=35) for T cell manipulation along with a haploidentical PTCy control cohort (n=45). Longitudinal cellular immune reconstitution data were analyzed conventionally and with a data science approach using clustering with dynamic time warping to determine the similarity between time-series of T cell subsets.

Combined Analysis of Early CD4 T Cell Counts and CMV Serostatus May Improve CMV Risk Assessment after Allogeneic Hematopoietic Cell Transplantation.

The incidence and severity of viral complications after cellular therapy are highly variable. Recent publications describe relevant interactions between the human Cytomegalovirus (CMV) and host immunity in recipients of allogeneic hematopoietic cell transplantation (HCT). Although immune monitoring is routinely performed in HCT patients, validated cut-off levels correlating with transplant outcomes such as survival or CMV reactivation are mostly limited to day +100, which is later than the median time for CMV reactivation in the absence of medical prophylaxis.

Low Soluble Programmed Cell Death Protein 1 Levels After Allogeneic Stem Cell Transplantation Predict Moderate or Severe Chronic GvHD and Inferior Overall Survival.

Programmed cell death protein-1 (PD-1) is an inhibitory co-receptor required for regulating immune responsiveness and maintaining immune homeostasis. As PD-1 can be released as bioactive soluble molecule, we investigated the clinical significance of soluble PD-1 (sPD-1) after allogeneic hematopoietic stem cell transplantation (HSCT) regarding graft-versus-host disease (GvHD), relapse, and overall survival (OS) in a mono-centric cohort of 82 patients. Compared to pre-HSCT and to healthy controls, post-HSCT sPD-1 plasma levels were significantly increased during an observation time of three months.

Decreased Soluble Human Leukocyte Antigen E Levels in Patients After Allogeneic Hematopoietic Stem Cell Transplantation Are Associated With Severe Acute and Extended Chronic Graft-versus-Host Disease and Inferior Overall Survival.

HLA-E is a member of the non-classical HLA molecules and by interaction with activating or inhibitory receptors of NK and T cells, HLA-E can lead to immune activation or suppression context-dependently. Recently, the non-classical HLA molecules gain more attention in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). Most studies so far have focused on the two most frequent genotypes (HLA-E*01:01 and HLA-E*01:03) and investigated their potential association with clinical endpoints of HSCT, like graft-versus-host disease (GvHD), relapse, and overall survival (OS).