Shiratori Souichi
Department of Hematology, Hokkaido University Faculty of Medicine.
Rinsho Ketsueki. 2021;62(8):1265-1274. doi: 10.11406/rinketsu.62.1265.
Graft versus host disease (GVHD) prophylaxis using antithymocyte globulin (ATG) has been shown for chronic GVHD inhibition effect by a series of randomized control trials in unrelated hematopoietic or peripheral blood stem cell transplantation (PBSCT). Lower doses of ATG have been used in recent studies, although the optimal dose of ATG remains undefined. Consequently, a multicenter phase II study of low-dose ATG (2 mg/kg Thymoglobulin) was conducted in patients undergoing human leukocyte antigen-matched PBSCT, showing the safety and efficacy for the prevention of both acute and chronic GVHD. In a nationwide retrospective study for ATG in unrelated PBSCT, the ATG group had a significantly lower incidence of chronic GVHD and a higher probability of GVHD- and relapse-free survival compared with the non-ATG group, although the dose of ATG used was low (1.0-3.0 mg/kg of Thymoglobulin). Regarding absolute lymphocyte count (ALC) before the administration of ATG, the incidences of grades III-IV acute GVHD and moderate-to-severe chronic GVHD were significantly higher in patients with high ALC before ATG. Conversely, the relapse rate was significantly higher in patients with low ALC before ATG, suggesting a strategy to individualize ATG dosing by modulating ATG doses according to ALC before ATG.
在无关供者造血或外周血干细胞移植（PBSCT）中，一系列随机对照试验表明，使用抗胸腺细胞球蛋白（ATG）预防移植物抗宿主病（GVHD）对慢性GVHD具有抑制作用。尽管ATG的最佳剂量尚未确定，但近期研究中已使用较低剂量的ATG。因此，对接受人类白细胞抗原匹配的PBSCT患者进行了一项低剂量ATG（2mg/kg兔抗人胸腺细胞球蛋白）的多中心II期研究，结果显示其在预防急性和慢性GVHD方面具有安全性和有效性。在一项针对无关PBSCT中使用ATG的全国性回顾性研究中，尽管使用的ATG剂量较低（1.0 - 3.0mg/kg兔抗人胸腺细胞球蛋白），但与未使用ATG的组相比，ATG组慢性GVHD的发生率显著降低，且无GVHD和无复发生存的概率更高。关于ATG给药前的绝对淋巴细胞计数（ALC），ATG给药前ALC较高的患者中III - IV级急性GVHD和中度至重度慢性GVHD的发生率显著更高。相反，ATG给药前ALC较低的患者复发率显著更高，这表明一种根据ATG给药前的ALC调整ATG剂量以实现ATG给药个体化的策略。
