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

Abstract

Allogeneic hematopoietic stem cell transplantation is increasingly used as treatment for patients with life-threatening blood diseases. Its curative potential is largely based on immune-mediated graft-versus-leukemia effects caused by donor T cells contained in the graft. Unfortunately, donor T cells are also the cause of graft-versus-host disease. The vast majority of human leukocyte antigen-matched allogeneic hematopoietic stem cell transplants are nowadays carried out with peripheral blood stem cells as the stem cell source. In comparison with bone marrows, peripheral blood stem cells contain more hematopoietic stem/progenitor cells but also one log more T cells. Consequently, the use of peripheral blood stem cells instead of bone marrow has been associated with faster hematologic recovery and a lower risk of relapse in patients with advanced disease, but also with a higher incidence of chronic graft-versus-host disease. These observations have been the basis for several studies aimed at assessing the impact of immunoregulation with anti-thymocyte globulin on transplantation outcomes in patients given human leukocyte antigen-matched peripheral blood stem cells from related or unrelated donors. After a brief introduction on anti-thymocyte globulin, this article reviews recent studies assessing the impact of anti-thymocyte globulin on transplantation outcomes in patients given peripheral blood stem cells from human leukocyte antigen-matched related or unrelated donors as well as in recipients of grafts from human leukocyte antigen haploidentical donors.

Copyright© Ferrata Storti Foundation.

Figures

Figure 1.

Quantification of ATG antibodies targeting specific human antigens. (adapted from Table 1 from Popow et al.) Black bars represent ATG-F data and white bars ATG-T data.

Figure 2.

Impact of ATG on transplantation outcomes in patients given grafts after reduced-intensity conditioning. (A) Forest plots showing the results of multivariate analyses from two large registry studies assessing the impact of ATG on transplantation outcomes either in patients with various hematologic malignancies [study from the Center for International Blood and Marrow Transplant Research (CIBMTR)] or in patients with acute myeloid leukemia in first complete remission [study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)]. (B) Relapse incidence and (C) progression-free survival in the subroup of patients from the EBMT study given peripheral blood stem cells (PBSC) after busulfan-based RIC (n=674, including 389 patients given ATG).