Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands.
Institute for Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Front Immunol. 2019 Mar 6;10:315. doi: 10.3389/fimmu.2019.00315. eCollection 2019.
Anti-thymocyte globulin (ATG) is a lymphocyte depleting agent applied in hematopoietic stem cell transplantation (HSCT) to prevent rejection and Graft-vs.-Host Disease (GvHD). In this study, we compared two rabbit ATG products, ATG-Genzyme (ATG-GENZ), and ATG-Fresenius (ATG-FRES), with respect to dosing, clearance of the active lymphocyte binding component, post-HSCT immune reconstitution and clinical outcome. Fifty-eigth pediatric acute leukemia patients ( = 42 ATG-GENZ, = 16 ATG-FRES), who received a non-depleted bone marrow or peripheral blood stem cell graft from an unrelated donor were included. ATG-GENZ was given at a dosage of 6-10 mg/kg; ATG-FRES at 45-60 mg/kg. The active component of ATG from both products was cleared at different rates. Within the ATG-FRES dose range no differences were found in clearance of active ATG or T-cell re-appearance. However, the high dosage of ATG-GENZ (10 mg/kg), in contrast to the low dosage (6-8 mg/kg), correlated with prolonged persistence of active ATG and delayed T-cell reconstitution. Occurrence of serious acute GvHD (grade III-IV) was highest in the ATG-GENZ-low dosage group. These results imply that dosing of ATG-GENZ is more critical than dosing of ATG-FRES due to the difference in clearance of active ATG. This should be taken into account when designing clinical protocols.
抗胸腺细胞球蛋白(ATG)是一种淋巴细胞耗竭剂,应用于造血干细胞移植(HSCT)中,以预防排斥反应和移植物抗宿主病(GvHD)。在这项研究中,我们比较了两种兔抗胸腺细胞球蛋白产品,即 ATG-Genzyme(ATG-GENZ)和 ATG-Fresenius(ATG-FRES),比较了剂量、活性淋巴细胞结合成分的清除率、HSCT 后免疫重建和临床结果。58 例儿科急性白血病患者(=42 例 ATG-GENZ,=16 例 ATG-FRES),均接受非耗竭性骨髓或无关供体外周血干细胞移植。ATG-GENZ 的剂量为 6-10mg/kg;ATG-FRES 的剂量为 45-60mg/kg。两种产品的 ATG 活性成分清除率不同。在 ATG-FRES 剂量范围内,活性 ATG 的清除或 T 细胞再出现没有差异。然而,高剂量的 ATG-GENZ(10mg/kg)与低剂量(6-8mg/kg)相比,与活性 ATG 的持续存在和 T 细胞重建的延迟相关。ATG-GENZ 低剂量组(6-8mg/kg)严重急性 GvHD(III-IV 级)的发生率最高。这些结果表明,由于活性 ATG 清除率的差异,ATG-GENZ 的剂量比 ATG-FRES 的剂量更为关键。在设计临床方案时应考虑到这一点。