TY  - JOUR
AU  - Leserer, Saskia
AU  - Graf, Theresa
AU  - Franke, Martina
AU  - Bogdanov, Rashit
AU  - Arrieta-Bolaños, Esteban
AU  - Buttkereit, Ulrike
AU  - Leimkühler, Nils
AU  - Fleischhauer, Katharina
AU  - Reinhardt, Hans Christian
AU  - Beelen, Dietrich W
AU  - Turki, Amin T
TI  - Time series clustering of T cell subsets dissects heterogeneity in immune reconstitution and clinical outcomes among MUD-HCT patients receiving ATG or PTCy.
JO  - Frontiers in immunology
VL  - 14
SN  - 1664-3224
CY  - Lausanne
PB  - Frontiers Media
M1  - DKFZ-2023-00714
SP  - 1082727
PY  - 2023
AB  - 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.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 in vivo 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.Consistent with published studies, no significant differences in clinical outcomes were observed at the cohort level between MUD-ATG and MUD-PTCy. However, cellular reconstitution revealed preferences for distinct T cell subpopulations associating with GVHD protection in each setting. Starting early after HCT, MUD-PTCy patients had higher regulatory T cell levels after HCT (p <0.0001), while MUD-ATG patients presented with higher levels of γδ T- or NKT cells (both p <0.0001). Time-series clustering further dissected the patient population's heterogeneity revealing distinct immune reconstitution clusters. Importantly, it identified phenotypes that reproducibly associated with impaired clinical outcomes within the same in vivo T cell manipulation platform. Exemplarily, patients with lower activated- and αβ T cell counts had significantly higher NRM (p=0.032) and relapse rates (p =0.01).The improved understanding of the heterogeneity of cellular reconstitution in MUD patients with T cell manipulation both at the cohort and individual level may support clinicians in managing HCT complications.
KW  - Humans
KW  - Time Factors
KW  - Immune Reconstitution
KW  - Antilymphocyte Serum
KW  - Hematopoietic Stem Cell Transplantation: adverse effects
KW  - Cyclophosphamide
KW  - Graft vs Host Disease
KW  - T-Lymphocyte Subsets
KW  - GVHD prophylaxis (Other)
KW  - anti-T-lymphocyte globulin (Other)
KW  - anti-thymocyte globulin (ATG) (Other)
KW  - dynamic time warping (DTW) (Other)
KW  - matched unrelated donor allogeneic hematopoietic stem cell transplantation (Other)
KW  - post-transplant cyclophosphamide (Other)
KW  - time-series (TS) model (Other)
KW  - unsupervised learning (Other)
KW  - Antilymphocyte Serum (NLM Chemicals)
KW  - Cyclophosphamide (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:37020562
C2  - pmc:PMC10067907
DO  - DOI:10.3389/fimmu.2023.1082727
UR  - https://inrepo02.dkfz.de/record/275345
ER  -