Both anti-T-lymphocyte globulin (ATLG-grafalon) and anti-thymocyte globulin (ATG-thymoglobulin) can prevent acute and chronic graft-versus-host-disease (GVHD) after allogeneic haematopoietic stem cell transplantation (HSCT). Because of distinct production characteristics, ATG and ATLG dysplay distinct affinities to T and other immune cells in vitro. Whether these differences could impact post-transplant outcomes has never been explored.MethodsIn this monocentric retrospective study, we compared post-transplant outcomes of 114 patients transplanted between January 2017 and September 2020 for an hematological malignancy with peripheral blood stem cells from a matched HLA 10/10 related (MRD, n= 25) or unrelated donor (MUD, n=89) and receiving either ATG (5 mg/kg; n=50) or ATLG (15 mg/kg for MRD and 30 mg/kg for MUD, n=64) for GVHD prophylaxis. We also compared naive and memory T cell subset, regulatory T and invariant NKT cell reconstitution after transplantation between the two groups. ResultsThe comparison of patients’ characteristics at transplantation showed that the two groups were comparable in terms of disease type (64% of AML and MDS in both groups), disease risk index (intermediate in 68% vs 71% in the ATG and ATG groups, respectively, p=0.6), CMV status and of donor (78% of MUD in both groups). Patients were older in the ATLG group (mean age 56 vs 51 years, p=0.04) and received more frequently a reduced intensity/toxicity conditioning regimen (72% vs 46%, p=0.01). Since ATLG was used more recently in our center, the median follow-up was longer in the ATG group (21 months vs 8.5 months, p< 0.001). At day 180, the cumulative incidence (CI) of grade II-IV acute GVHD was 49% (95% CI 34-64%) in the ATG vs 25% (95% CI 12-33%) in ATLG group, (p=0.005) (Figure 1). CI of CMV (p=0.98) and EBV (p=0.43) reactivations were comparable between the 2 groups. Incidence of chronic GVHD was similar in both groups (62% vs 72%, in the ATG vs ATLG groups at 2 years) with low incidences of moderate and severe cGVHD (29% vs 19 %, in the ATG vs ATLG groups at 2 years). At one year post-HSCT, non relapse mortality was comparable between the 2 groups (9% in both), while relapse incidence was higher in the ATG group (40% vs 16%, in the ATG vs ATLG groups, p= 0.016). At 2 years, extrapolated overall and GVHD-free, relapse free survival (GRFS) were not significantly different between the 2 groups (61% vs 71% and 54% vs 67% in the ATG vs ATLG groups, respectively). In terms of immune reconstitution, we observed was a more profound depletion of naive CD4 and CD8 T cells and reduced PD1 expressing on CD8 T cells in patients receiving ATLG in comparison to those receiving ATG between day 14 and day 90 post-HSCT while levels of regulatory cells were similar.ConclusionOur results suggest that ATLG may better prevent the occurrence of severe acute GVHD by differential effect on T cell reconstitution and activation, without increasing the incidence of relapse and of viral reactivation. These results should be confirmed in a prospective randomized trial.