Effective prevention of GVHD using in vivo T-cell depletion with anti-lymphocyte globulin in HLA-identical or -mismatched sibling peripheral blood stem cell transplantation

Abstract

To investigate the impact of anti-lymphocyte globulin (ATG-Fresenius) as part of the HLA-sibling transplantation, we evaluated 238 patients (median age 48 years) with different diagnoses (AML, ALL, CML and lymphoproliferative disorders). A total of 79 patients received ATG and 159 patients did not. In the ATG group, there were more HLA-mismatched donors (6% vs 1%, p ¼ 0.02), bad risk patients (70% vs 55%, P ¼ 0.04), reduced intensity conditioning (RIC) regimens (65% vs 34%, P ¼ o0.001) and older patients (median age 51 vs 48 years, P ¼ 0.002). The median time to leukocyte engraftment was significantly faster in the non-ATG group (13 vs 15 days, P o 0.001). EBV reactivation was more often seen in the ATG group (9% vs 2%, P ¼ 0.05). Cumulative incidence of acute and chronic GVHD was less observed in the ATG group (27% vs 40%, P ¼ 0.004, and 33% vs 54%, P ¼ 0.002). The cumulative incidence rates of non-relapse mortality and of relapse at 5 years were 20 and 34%, respectively, for ATG and 34 and 29%, respectively, for non-ATG (P ¼ 0.06 and P ¼ 0.3). ATG can prevent GVHD without an obvious risk of relapse but should be confirmed in a randomized study.

Lower dose anti-thymocyte globulin for GvHD prophylaxis results in improved survival after allogeneic stem cell transplantation

“…However, with the exception of one study with matched-related HSCT only, 21 these studies did not reach statistical significance. [7][8][9][10]13,22 The survival benefit shown here may be due to an improved selection of patients receiving ATG. Although the imbalance of known risk factors was adjusted for by statistical analysis, larger series of patients need to be analyzed for confirmation.…”

“…This effect had already been reported in previous studies. 5,7,9,10,22,23 Incidence of CMV and EBV reactivations, as well as symptomatic viral infections and bacterial BSI, but not invasive fungal infections were increased especially when using higher dose ATG. This can be attributed to the immunosuppressive effect of ATG.…”

“…Other groups had similar findings, for example, Bacigalupo et al, 10 who found more lethal infections with ATG, but others did not find any difference in infection-related mortality. 7,13,22 Previous studies had only analyzed fatal infections or patients with 41 any infectious episode without further differentiation. We analyzed infections as viral reactivation, symptomatic viral infection, bacterial and fungal infection within 6 months from transplantation.…”

Anti-thymocyte globulin as graft- versus -host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…A number of phase II studies have assessed the impact of rabbit ATG in patients given unmodified grafts after myeloablative conditioning [46][47][48][49][50][51][52] (Table 2). Collectively, these studies suggested that ATG decreased the incidence of grade III-IV acute and chronic GVHD without increasing non-relapse mortality (some studies even found lower non-relapse mortality with ATG), increased the incidence of post-transplantation lymphoproliferative disorders, and improved quality of life.…”

Autologous apoptotic cells preceding transplantation enhance survival in lethal murine graft-versus-host models

“…4,5 An alternative approach is to engineer the graft including T-cell depletion or administration of various subsets of T cells, such as regulatory T cells (Tregs). [6][7][8] Despite the knowledge of the impact of host APCs on GVHD induction, only a few preclinical studies have focused on targeting APCs to prevent GVHD induction. [9][10][11][12] Professional APCs internalize antigens, display peptides on their surface, and express costimulatory molecules that guide T-cell activation.…”