Post-transplant anti-thymocyte globulin exposure predicts graft-versus-host disease and donor chimerism outcomes in reduced intensity conditioning allogeneic stem cell transplantation
- Author(s)
- Koo, RM; Davis, J; Ludford-Menting, M; Wong, E; Koldej, R; Ritchie, D;
- Journal Title
- Frontiers in Immunology
- Publication Type
- Research article
- Abstract
- Although anti-thymocyte globulin (ATG) is commonly used as prophylaxis against graft-versus-host disease (GVHD) following allogeneic haematopoietic stem cell transplantation (alloSCT), there is considerable inter-patient variability in ATG exposure. The impact of ATG exposure in outcomes following reduced intensity conditioning (RIC)-alloSCT remains unknown. We explored the impact of post-transplant ATG exposure (PT-ATG-exp) in 68 adults with haematological malignancies undertaking first RIC-alloSCT with ATG (Thymoglobulin, total dose 4.5mg/kg, day -3 to -1 alloSCT). Post-transplant ATG exposure was determined by area under the curve (AUC) through analysis of sera collected at standardised timepoints. Post-transplant ATG exposure range was highly variable [46-420 arbitrary units (AU) per day/mL]. Day 0 ATG concentration and day 0-14 ATG AUC highly correlated with PT-ATG-exp (R = 0.93 and 0.99, respectively, P < 0.001). Using a Cox proportional hazards model, patients with PT-ATG-exp between 80-135 AU per day/mL had inferior 2-year GRFS compared to the remainder of the cohort [25% (95% CI, 11%-56%) vs 54% (95% CI, 40%-73%), P = 0.02; HR 2.01 (95% CI, 1.04-3.86, P = 0.04] due to higher incidence of grade III-IV acute GVHD [33% (95% CI, 16%-51%) vs 12% (95% CI, 4%-24%), P = 0.034; HR 2.95 (95% CI, 0.99-8.83, P = 0.05)]. Recipients with the highest PT-ATG-exp (quartile 4: 185-420 AU per ml/day) had the lowest incidence of grade III-IV acute GVHD (0% at 180-days) but also lowest median CD3(+) chimerism (85%) and highest incidence of mixed donor chimerism (CD3(+): 93% and CD3(-): 33%) at day 100. In this analysis, PT-ATG-exp influenced post-transplant outcomes including GVHD incidence and donor chimerism following in RIC-alloSCT.
- Publisher
- Frontiers
- Keywords
- Humans; *Graft vs Host Disease/prevention & control/etiology/diagnosis; *Antilymphocyte Serum/administration & dosage/therapeutic use; *Transplantation Conditioning/methods/adverse effects; Female; *Hematopoietic Stem Cell Transplantation/adverse effects/methods; Male; Adult; Middle Aged; Transplantation, Homologous; *Hematologic Neoplasms/therapy; Aged; *Transplantation Chimera; Treatment Outcome; Young Adult; allogeneic stem cell transplantation (allo-SCT); anti-thymocyte globulin (ATG); chimerism after allo-HSCT; graft-versus-host disease (GVHD); haematological malignancies; pharmacodynamics (PD); pharmacokinetics; reduced intensity conditioning (RIC)
- Department(s)
- Haematology
- Publisher's Version
- https://doi.org/10.3389/fimmu.2026.1879058
- Open Access at Publisher's Site
https://doi.org/10.3389/fimmu.2026.1879058- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-09-16 04:43:31
Last Modified: 2026-09-16 04:43:41