Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
Blood Adv. 2019 Jan 22;3(2):105-115. doi: 10.1182/bloodadvances.2018025643.
Antithymocyte globulin (ATG) is widely used to reduce acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD). To clarify the different impacts of ATG for conditioning across different donor types, we retrospectively analyzed patients with acute leukemia (n = 6617) who underwent hematopoietic stem cell transplantation between 2008 and 2015 with ATG (n = 279) or without ATG (n = 6338). Because thymoglobulin is the only ATG drug approved for GVHD prophylaxis in Japan since September 2008, we included thymoglobulin alone in the present analysis. The survivors' median follow-up time was 1081 days. Patients were categorized into 5 groups: cord blood (CB; n = 1915), matched related donor (n = 1772), 1-antigen mismatched related donor (1-MMRD; n = 225), matched unrelated donor (MUD; n = 1742), and 1-allele mismatched unrelated donor (1-MMUD; n = 963). In multivariate analysis, ATG decreased overall survival (hazard ratio [HR], 1.403; = .054) and GVHD-free/relapse-free survival (GRFS) (HR, 1.458; = .053) in association with increased nonrelapse mortality (NRM) (HR, 1.608; 03) with CB, whereas it improved GRFS (HR, 0.515; < .01) and decreased grades II to IV aGVHD (HR, 0.576; < .01), extensive cGVHD (HR, 0.460; = .02), and NRM (HR, 0.545; = .03) with 1-MMUD. ATG did not impact survival with 1-MMRD and MUD. The use of ATG in conditioning is beneficial due to the reduction in acute/chronic GVHD without increasing NRM or disease relapse only in 1-MMUD transplantation. On the other hand, ATG is not recommended for CB transplantation.
抗胸腺细胞球蛋白(ATG)被广泛用于减少急性移植物抗宿主病(aGVHD)和慢性移植物抗宿主病(cGVHD)。为了阐明不同供体类型的 ATG 对预处理的不同影响,我们回顾性分析了 2008 年至 2015 年间接受造血干细胞移植的急性白血病患者(n=6617),其中 ATG(n=279)或无 ATG(n=6338)。由于自 2008 年 9 月以来,胸腺球蛋白是日本唯一一种批准用于预防 GVHD 的 ATG 药物,因此我们在本分析中仅包括胸腺球蛋白。幸存者的中位随访时间为 1081 天。患者分为 5 组:脐带血(CB;n=1915)、匹配相关供体(n=1772)、1 抗原错配相关供体(1-MMRD;n=225)、匹配无关供体(MUD;n=1742)和 1 等位基因错配无关供体(1-MMUD;n=963)。多变量分析显示,ATG 降低了总体生存率(风险比[HR],1.403;=0.054)和无 GVHD/无复发生存率(GRFS)(HR,1.458;=0.053),与非复发死亡率(NRM)增加相关(HR,1.608;=0.03)与 CB 相关,而与 1-MMUD 相关时,GRFS 改善(HR,0.515;<.01)和 II 至 IV 级 aGVHD(HR,0.576;<.01)、广泛 cGVHD(HR,0.460;=0.02)和 NRM(HR,0.545;=0.03)降低。ATG 对 1-MMRD 和 MUD 无影响。由于急性/慢性 GVHD 的减少而不增加 NRM 或疾病复发,ATG 在 1-MMUD 移植中的应用是有益的。另一方面,不建议在 CB 移植中使用 ATG。