Post-transplant anti-thymocyte globulin exposure predicts graft-versus-host disease and donor chimerism outcomes in reduced intensity conditioning allogeneic stem cell transplantation

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.