Division of Hematology, Jichi Medical University Saitama Medical Center, 1-847, Amanuma-cho, Omiya-ku, Saitama-city, Saitama, 330-8503, Japan.
Department of Hematology/Oncology, Kyoto University Hospital, Kyoto, Japan.
Ann Hematol. 2020 May;99(5):1099-1110. doi: 10.1007/s00277-020-03995-7. Epub 2020 Mar 23.
For patients without an HLA-matched donor, an HLA-mismatched unrelated donor (MMUD) has been considered as an alternative donor in allogeneic hematopoietic cell transplantation (allo-HCT). We conducted a nationwide retrospective study to compare the transplant outcomes among 1-, 2-, and 3-locus (allele/antigen) mismatched unrelated donors (1MMUD n = 2044, 2MMUD n = 492, and 3MMUD n = 73) in allo-HCT and to assess the impact of antithymocyte globulin (ATG) in allo-HCT from 1-3MMUD. 2MMUD and 3MMUD were independent significant adverse factors for grade III-IV acute graft-versus-host disease (GVHD) (hazard ratio [HR] 1.72, p < 0.001 and HR 2.48, p < 0.001), non-relapse mortality (NRM) (HR 1.47, p < 0.001 and HR 2.00, p < 0.001), and overall survival (OS) (HR 1.21, p = 0.0066 and HR 1.60, p = 0.0015). Conversely, the use of ATG was an independent favorable factor for grade III-IV acute GVHD (HR 0.43, p < 0.001), NRM (HR 0.51, p < 0.001), and OS (HR 0.74, p = 0.0012). On the other hand, HLA compatibility and the use of ATG were not associated with a risk of relapse. An interaction test between the number of HLA mismatches and the use of ATG revealed that the effect of ATG on NRM and OS in the 2MMUD group was significantly less than that in the 1MMUD group (HR 1.53, p = 0.036 and HR 2.34, p = 0.0046). This study indicated that the number of HLA mismatches and the use of ATG were significantly associated with not only GVHD, but also NRM and OS. Whereas the use of ATG could improve transplant outcomes in allo-HCT from 1MMUD, its effectiveness with 2MMUD and 3MMUD was limited.
对于没有 HLA 匹配供体的患者，HLA 错配无关供体 (MMUD) 已被视为同种异体造血细胞移植 (allo-HCT) 中的另一种供体选择。我们进行了一项全国性回顾性研究，比较了在 allo-HCT 中，1 个、2 个和 3 个 HLA 位点（等位基因/抗原）错配无关供体（1MMUD n=2044、2MMUD n=492 和 3MMUD n=73）之间的移植结果，并评估了抗胸腺细胞球蛋白 (ATG) 在 1-3MMUD 中的 allo-HCT 中的影响。2MMUD 和 3MMUD 是 3 级-4 级急性移植物抗宿主病 (GVHD)（危险比 [HR] 1.72，p<0.001 和 HR 2.48，p<0.001）、非复发死亡率（NRM）（HR 1.47，p<0.001 和 HR 2.00，p<0.001）和总生存（OS）（HR 1.21，p=0.0066 和 HR 1.60，p=0.0015）的独立不良因素。相反，ATG 的使用是 3 级-4 级急性 GVHD（HR 0.43，p<0.001）、NRM（HR 0.51，p<0.001）和 OS（HR 0.74，p=0.0012）的独立有利因素。另一方面，HLA 相容性和 ATG 的使用与复发风险无关。HLA 错配数量和 ATG 使用之间的交互测试表明，ATG 在 2MMUD 组中的 NRM 和 OS 中的作用明显小于 1MMUD 组（HR 1.53，p=0.036 和 HR 2.34，p=0.0046）。这项研究表明，HLA 错配数量和 ATG 的使用不仅与 GVHD 相关，而且与 NRM 和 OS 相关。虽然 ATG 的使用可以改善 allo-HCT 中来自 1MMUD 的移植结果，但它在 2MMUD 和 3MMUD 中的效果有限。
