Dynamic immune profiling enables early distinction between gastrointestinal GVHD and viral diarrhea after hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for hematologic malignancies, yet diarrhea after allo-HSCT—mainly due to gastrointestinal graft-versus-host disease (GI-GVHD) or viral infection—remains a major clinical challenge. Early etiological differentiation is essential for appropriate management. This study aimed to develop an immune-based predictive model by dynamically monitoring lymphocyte subsets and cytokines after allo-HSCT. Among 232 patients who underwent allo-HSCT at Beijing Lu Daopei Hospital between 2021 and 2024, 58 developed biopsy-confirmed post-transplant (post-HSCT) diarrhea, comprising 34 cases of GI-GVHD and 24 cases of viral enteritis. Immune profiles were measured one week prior to diarrhea onset, as well as at weeks 4 and 5 post-HSCT. Predictive features were selected using LASSO and logistic regression to construct single- and multi–time–point models, which were validated using nomogram, calibration, and decision curve analyses. At the pre-diarrhea point, patients with aGVHD had higher Reg3α, CD3⁺T%, CD8⁺T%, naive CD4⁺/CD4⁺T%, and Th2/CD4⁺T%, but lower NK count and NK% (all P < 0.05). The single-time-point model achieved good discrimination (AUC = 0.799), while the multi–time-point model integrating nine dynamic parameters showed superior accuracy (AUC = 0.908). Conclusions: Dynamic immune profiling may aid in the early distinction between GI-GVHD and viral enteritis, highlighting its potential as a tool for immunological surveillance to guide intervention after allo-HSCT.