Effective Prevention of Acute and Chronic Graft-Versus-Host Disease with Anti-Lymphocyte Globulin (ATG) without Increase of Relapse in HLA-Identical Sibling Peripheral Blood Stem Cell Transplantation.

Abstract 3055

Acute and chronic graft versus host disease (GvHD) are severe complications after allogeneic stem cell transplantation but occurrence of GvHD is associated with reduced risk of relapse. Therefore, strategies to prevent GvHD without increasing the risk of relapse are urgently needed.

We investigate retrospectively whether anti-lymphocyte globulin (ATG Fresenius®, Fresenius Biotech, Graefelfing, Germany) as part of the conditioning regimen may reduce the risk of GvHD without increasing the risk of relapse after peripheral blood stem cell transplantation from HLA-identical siblings or HLA-compatible relatives. Out of 462 patients who received HLA-identical stem cell transplantation between 1990 and 2011 in our institution, we selected 238 consecutive patients who received allogeneic peripheral blood stem cell grafts after the year 2000. The median age of the patients was 48 years (r.,18–73y) and diagnosis were: AML (n=93), ALL (n=24), CML (n=25), MDS (n=23) or lympho-proliferative disorders (n=73). Patients were classified as good risk (n=95) or bad risk (n=143). 79 patients did receive ATG within the conditioning regimen with a median dose of 30mg/kg (r., 20–90mg/kg) and 159 patients did not receive ATG. In the ATG group there were more HLA mismatch donors (6% vs. 1%, p=0.02), more bad risk patients (70% vs. 50%, p=0.04), more reduced intensity conditioning regimens (65% vs. 34%, p< 0.001) and older patients (median age 50 vs. 46 years, p=0.03). Acute GvHD grade I to IV was less observed in the ATG group (27% vs. 40%, p= 0.04), but the difference in severe GvHD grade III and IV did not show statistical significance (10% vs. 18%, p=0.1). Chronic GvHD was less observed in the ATG group (30% vs. 52%, p=0.002), which was most obvious for extensive chronic GvHD (14% vs. 40%, p<0.001). After a median follow up of 57 months in the non-ATG and 63 months in the ATG group the cumulative incidence of non-relapse mortality at 5 years was 20% for the ATG and 34% for the non-ATG group (p=0.06) and the cumulative incidence of relapse at 5 years was 34% for the ATG group and 29% for the non –ATG group (p=0.2), resulting in a comparable 5 year progression-free (ATG: 46% and non-ATG 37%, p=0.5) and overall survival (ATG: 54% and non-ATG 46%, p=0.4).

This retrospective study shows that ATG can prevent severe chronic GvHD without obvious risk of relapse and similar PFS and OS in HLA identical sibling transplantation. A randomized trial including QoL measurement comparing ATG vs. no ATG in HLA identical sibling transplantation is ongoing (registered NCT 00678275).