Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama-city, Saitama, 330-8503, Japan.
Int J Hematol. 2019 Jul;110(1):22-29. doi: 10.1007/s12185-019-02597-y. Epub 2019 Jan 24.
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.
当无法获得 HLA 匹配的相关或无关供体时，HLA 单一位点不合的无关供体（1MMUD）通常被认为是异基因造血干细胞移植（allo-HCT）中的替代供体。然而，HLA 不匹配仍然是急性和慢性移植物抗宿主病（GVHD）的主要危险因素。抗胸腺细胞球蛋白（ATG）已被用于预防急性和慢性 GVHD，多项研究表明，使用 ATG 与降低急性和慢性 GVHD 相关，从而提高生活质量。然而，高剂量的 ATG 可能导致致命感染、复发或延迟植入。用于 MMUD 的最佳 ATG 剂量仍不清楚。最佳 ATG 剂量应根据减少 GVHD 和复发、致命感染和/或延迟植入的风险之间的精细平衡来确定。有趣的是，一些最近的亚洲研究的结果表明，低剂量 ATG 可能会改善非复发死亡率和总生存率，而不会增加 HLA 不合的无关供体 allo-HCT 中的复发或致命感染。预计在日本的一项随机对照试验将证实这些结果。此外，药代动力学/药效学研究可能有助于确定个性化的最佳 ATG 剂量。
