Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Engineering Technology Research Center of Cell Therapy and Clinical Translation, Shanghai Science and Technology Committee (STCSM), Shanghai, China.
Cell Transplant. 2022 Jan-Dec;31:9636897221079739. doi: 10.1177/09636897221079739.
Standard anti-thymocyte globulin (ATG) weight-based dosing often resulted in highly variable ATG exposure, which had profound effects on relapse and survival, especially in recipients with relatively low absolute lymphocyte count (ALC) before conditioning. Data regarding rabbit ATG pharmacokinetics and pharmacodynamics in the setting of HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) is lacking. We conducted a retrospective study on 90 consecutive patients who underwent haplo-PBSCT with low dose rabbit ATG (5 mg/kg) plus low dose post-transplant cyclophosphamide (50 mg/kg) based regimen for graft-versus-host disease (GvHD) prophylaxis. We compared serum concentration of ATG and post-transplant results between patients with ALC<500/μl and ALC≥500/μl before conditioning. Patients with ALC<500/μl had higher ATG concentrations, delayed immune reconstitution, lower incidence of grade II-IV acute GvHD (0 . 19.42%, = 0.043), higher risk of Epstein-Barr virus infection within 100 days post-transplant (47.78% . 22.22%, = 0.020) and 1-year relapse rate (33.33% 11.59%, = 0.041), and lower 1-year overall survival (OS) (52.38% 79.71%, = 0.004), 1-year relapse free survival (RFS) (47.62% 75.36% for RFS, = 0.014), and 1-year GvHD free relapse-free survival (GRFS) (42.89% 65.22%, = 0.043). ALC<500/μl before conditioning was a significant poor risk factor for relapse, OS, RFS, and GRFS.
标准的抗胸腺细胞球蛋白（ATG）基于体重的给药方案常常导致 ATG 暴露高度变化，这对复发和生存有深远影响，特别是在预处理前绝对淋巴细胞计数（ALC）相对较低的受者中。关于 HLA 单倍体外周血造血干细胞移植（haplo-PBSCT）中兔 ATG 的药代动力学和药效动力学的数据尚缺乏。我们对 90 例接受低剂量兔 ATG（5mg/kg）联合低剂量移植后环磷酰胺（50mg/kg）方案预防移植物抗宿主病（GVHD）的 haplo-PBSCT 连续患者进行了回顾性研究。我们比较了预处理前 ALC<500/μl 和 ALC≥500/μl 的患者的 ATG 血清浓度和移植后结果。ALC<500/μl 的患者具有更高的 ATG 浓度、延迟的免疫重建、较低的 II-IV 级急性 GVHD 发生率（0.19. 42%，=0.043）、移植后 100 天内 EBV 感染的风险较高（47.78%. 22.22%，=0.020）和 1 年复发率（33.33%. 11.59%，=0.041），以及较低的 1 年总生存率（OS）（52.38%. 79.71%，=0.004）、1 年无复发生存率（RFS）（47.62%. 75.36%，=0.014）和 1 年无 GVHD 无复发生存率（GRFS）（42.89%. 65.22%，=0.043）。预处理前 ALC<500/μl 是复发、OS、RFS 和 GRFS 的显著不良危险因素。
