Longitudinal TCR Repertoire Profiling Reveals Early Immune Perturbations Preceding Post-Transplant Complications

Early complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including graft-versus-host disease (GVHD) and viral reactivation, remain major causes of post-transplant morbidity, but whether immune perturbations precede these events remains unclear. We performed longitudinal TCR{beta} repertoire profiling in 108 allo-HSCT recipients and their corresponding donors at baseline and three early post-transplant time points to characterize immune reconstitution dynamics. Reduced baseline TCR diversity was most strongly associated with subsequent Epstein-Barr virus (EBV) reactivation, whereas cytomegalovirus (CMV) reactivation was more closely linked to post-transplant repertoire remodeling characterized by clonal expansion and reduced donor-recipient repertoire similarity. Sequence-based predictive modeling demonstrated meaningful discrimination, with fusion models achieving area under the curve (AUC) values of 0.745 for CMV, 0.819 for EBV, and 0.834 for GVHD. Temporal analyses further revealed complication-specific predictive windows. These findings indicate that major post-transplant complications are preceded by detectable immune perturbations and support the potential utility of TCR repertoire monitoring for early risk stratification after transplantation.