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.
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