Impact of Anti-T-lymphocyte globulin dosing on GVHD and Immune reconstitution in matched unrelated myeloablative peripheral blood stem cell transplantation

Abstract

Data on the influence of different Anti-lymphocyte globulin (ATLG) doses on graft versus host disease (GVHD) incidence and immune reconstitution in matched unrelated (MUD) allogeneic Stem cell transplantation (allo-SCT) is limited. This retrospective study conducted at the University Medical-Center Hamburg compares GVHD and Immune reconstitution after myeloablative MUD (HLA 10/10) PBSC allogeneic stem cell transplant between 30 mg/Kg (n = 73) and 60 mg/Kg (n = 216) ATLG. Detailed phenotypes of T, B natural killer (NK), natural killer T (NKT) cells were analyzed by multicolor flow at day 30, 100, and 180 posttransplant. Neutrophil and platelet engraftments were significantly delayed in the 60 mg/kg group with a higher Cumulative incidence of Infections (67% vs 75% p = 0.049) and EBV (21% vs 41% p = 0.049) reactivation at day 100 in this group. In the 30 mg/kg group, we observed a faster reconstitution of naïve-B cells (p < 0.0001) and γδ T cells (p = 0.045) at day+30 and a faster naïve helper T-cell (p = 0.046), NK-cells (p = 0.035), and naïve B-cell reconstitution (p = 0.009) at day+180. There were no significant differences in aGVHD, cGVHD, NRM, RI, PFS, and OS between the groups. The choice of ATLG dose has significant impact on IR but not on GVHD after MUD-allo-SCT. Higher doses are associated with delayed engraftment and increased infections.

Fig. 1. Comparison of two different ATLG dose for GvHD Prevention after unrelated allogeneic stem cell transplantation.

a Comparison of neutrophil engraftment between 30 mg/kg and 60 mg/kg ATLG. b Incidence of infections after 30 mg/kg and 60 mg/kg ATLG.

Fig. 2. Comparison of two different ATLG dose for GvHD Prevention after unrelated allogeneic stem cell transplantation.

a comparison of overall survival (OS) between 30 mg/kg and 60mg/kg ATLG. b comparison of disese-free survival (DFS between 30 mg/kg and 60 mg/kg ATLG and c comparison of cumulative incidence of non-relapse mortality (NRM) between 30 mg/kg and 60 mg/kg ATLG.

Fig. 3. Comparison of two different ATLG dose for GvHD Prevention after unrelated allogeneic stem cell transplantation.

Comparison of imnune reconstitution between 30 mg/kg and 60 mg/kg ATLG after transplantation regarding (a) gamma-delta T cells (b) naive T cells c Natural Killer (NK) cells and d naive B-cells.

Fig. 4. Comparison of Immune reconstitution.

a of gamma-delta T cells post allo-SCT between 30 mg/Kg ATLG vs 60 mg/Kg ATLG. b of naïve T cells post allo-SCT between 30 mg/Kg ATLG vs 60 mg/Kg ATLG. c of NK-Cells post allo-SCT between 30 mg/Kg ATLG vs 60 mg/Kg ATLG. d of naïve B-cells post allo-SCT between 30 mg/Kg ATLG vs 60 mg/Kg ATLG.