Effect of antithymocyte globulin on HLA-mismatched unrelated transplantation

Abstract

HLA 1-locus-mismatched unrelated donors (1MMUD) are often considered as alternative donors in allogeneic hematopoietic stem-cell transplantation (allo-HCT) when an HLA-matched related or unrelated donor is unavailable. However, HLA mismatch remains a major risk factor for acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) has been used to prevent acute and chronic GVHD, and multiple studies have shown that use of ATG is associated with decreased acute and chronic GVHD, which is associated with improved QOL. However, at high doses, ATG may lead to an increase in fatal infection, relapse, or delayed engraftment. The optimal ATG dose for MMUD remains unclear. The optimal ATG dose should be determined based on a fine balance between the reduction of GVHD and the risk of relapse, fatal infection, and/or delayed engraftment. Interestingly, promising results from some recent Asian studies suggest that a low dose of ATG may improve non-relapse mortality and overall survival without increasing relapse or fatal infection in allo-HCT from an HLA-mismatched unrelated donor. A randomized control trial is expected to confirm these results in Japan. In addition, pharmacokinetic/pharmacodynamic studies may help to identify the personalized optimal ATG dose.

Graft-versus-host-disease prophylaxis with ATG or PTCY in patients with lymphoproliferative disorders undergoing reduced intensity conditioning regimen HCT from one antigen mismatched unrelated donor

“…Along with a comparable acute GvHD we also observed similar rates of chronic GvHD in both ATG and PTCY groups. This finding may be explained by the mechanism of action of ATG, which acts not only with an extensive in vivo T-cell depletion and with expansion of regulatory T cells, but by also targeting B cells [ 25 , 26 ]. Given that both donor T and B cells are crucial in the development of chronic GvHD, ATG prolonged inhibitory effect on these cells may help in preventing this complication in the long term [ 27 ].…”

Quantification of T Cell Binding Polyclonal Rabbit Anti-thymocyte Globulin in Human Plasma with Liquid Chromatography Tandem-Mass Spectrometry

“…GvHD is likely caused by the transplanted donor T cells recognizing major and minor histocompatibility complex proteins on the recipient antigen-presenting cells (3). Prophylaxis with polyclonal anti-thymocyte globulin (ATG) which targets different antigens expressed on, e.g., T cells, B cells, natural killer cells, and dendritic cells lead to depletion of these cells from the host blood and peripheral lymphoid tissues (4). Though ATG is used as a rescue therapy for acute rejection in solid organ transplantation, its main application is in hematology to treat and prevent acute and chronic GvHD following HCT in patients with hematologic cancers (4,5).…”

“…Prophylaxis with polyclonal anti-thymocyte globulin (ATG) which targets different antigens expressed on, e.g., T cells, B cells, natural killer cells, and dendritic cells lead to depletion of these cells from the host blood and peripheral lymphoid tissues (4). Though ATG is used as a rescue therapy for acute rejection in solid organ transplantation, its main application is in hematology to treat and prevent acute and chronic GvHD following HCT in patients with hematologic cancers (4,5). However, the overall survival remains similar between ATGtreated and ATG-untreated patients due to increased risk of relapse and infections in ATG-treated patients (6)(7)(8)(9).…”

Guest Editorial: Are “alternative” stem cell sources still alternative in the new era?

“…More recently, transplantation from HLA single locus-mismatched related and unrelated donors as an alternative stem cell source has been performed increasingly, with acceptable outcomes; however, overall survival using stem cells from such donors has been inferior to that in matched transplantation. As reviewed by Dr. Koji Kawamura [1], the use of lowdose anti-thymocyte globulin has improved outcomes of one locus-mismatched unrelated bone marrow transplantation, which are now nearly comparable to those of HLA-matched unrelated bone marrow transplantation.…”