Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Alberta Health Services, Calgary, AB, Canada.
Blood Adv. 2019 May 14;3(9):1394-1405. doi: 10.1182/bloodadvances.2018030247.
It remains unknown why rabbit antithymocyte globulin (ATG; Thymoglobulin) has not affected relapse after hematopoietic cell transplantation (HCT) in randomized studies. We hypothesized that high pre-HCT ATG area under the curve (AUC) would be associated with a low incidence of relapse, whereas high post-HCT AUC would be associated with a high incidence of relapse. We measured serum levels of ATG capable of binding to mononuclear cells (MNCs), lymphocytes, T cells, CD4 T cells, or CD33 cells. We estimated pre- and post-HCT AUCs in 152 adult recipients of myeloablative conditioning and blood stem cells. High pre-HCT AUCs of MNC- and CD33 cell-binding ATG were associated with a low incidence of relapse and high relapse-free survival (RFS). There was a trend toward an association of high post-HCT AUC of lymphocyte-binding ATG with a high incidence of relapse and low RFS. High pre-HCT AUCs were also associated with faster engraftment and had no impact on graft-versus-host disease (GVHD) or fatal infections. High post-HCT AUCs were associated with a low risk of GVHD, seemed associated with an increased risk of fatal infections, and had no impact on engraftment. In conclusion, pre-HCT AUC seems to have a positive, whereas post-HCT AUC seems to have a negative, impact on relapse.
尚不清楚为什么兔抗胸腺细胞球蛋白（ATG；Thymoglobulin）在随机研究中并未影响造血细胞移植（HCT）后的复发。我们假设高 HCT 前 ATG 曲线下面积（AUC）与复发发生率低有关，而高 HCT 后 AUC 与复发发生率高有关。我们测量了能够与单核细胞（MNC）、淋巴细胞、T 细胞、CD4 T 细胞或 CD33 细胞结合的 ATG 血清水平。我们估计了 152 名接受清髓性调理和造血干细胞的成年受者的 HCT 前和 HCT 后 AUC。MNC 和 CD33 细胞结合 ATG 的高 HCT 前 AUC 与复发发生率低和无复发生存率（RFS）高有关。淋巴细胞结合 ATG 的高 HCT 后 AUC 与复发发生率高和 RFS 低之间存在关联的趋势。高 HCT 前 AUC 还与更快的植入有关，对移植物抗宿主病（GVHD）或致命感染没有影响。高 HCT 后 AUC 与 GVHD 的低风险相关，似乎与致命感染的风险增加相关，对植入没有影响。总之，HCT 前 AUC 似乎具有积极的影响，而 HCT 后 AUC 似乎具有消极的影响。
