Department of Medicine, West Michigan Cancer Center, Columbus, Ohio.
Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
Biol Blood Marrow Transplant. 2019 Oct;25(10):1993-2001. doi: 10.1016/j.bbmt.2019.06.014. Epub 2019 Jun 20.
The appropriate dose of antithymocyte globulin (ATG) to be used in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) is yet to be determined. We retrospectively analyzed the outcomes of patients who underwent unrelated or mismatch related RIC allo-HSCT for hematologic malignancies and received r-ATG (4.5 mg/kg, 141 patients) versus R-ATG (6 mg/kg, 216 patients). There was a higher incidence of cytomegalovirus (P < .001) and Epstein-Barr virus viremia (P =.03) in the R-ATG group than in the r-ATG group. The cumulative incidences of acute graft-versus-host disease (aGVHD) grades II to IV at day 180 in the r-ATG and R-ATG groups were 59% and 44% (P = .006) and grades III to IV 20% and 12% (P = .029), respectively. In multivariable models adjusting for disease diagnosis, the risk of aGVHD grades III to IV did not reach statistical significance (P = .087). The respective cumulative incidences of chronic GVHD in the r-ATG and R-ATG groups were 26% and 15% (P = .10), respectively. There were no significant differences in relapse rate (P = .24), nonrelapse mortality (P = .96), progression-free survival (P = .24), overall survival (P = .70), and GVHD-free relapse-free survival (P = .24). In this retrospective analysis, aGVHD incidence was higher in those treated with r-ATG compared with R-ATG, but this did not translate into significant differences of clinical outcome. Given the increasing use of RIC allo-HSCT for treating malignant hematologic conditions, the correct dose and schedule of ATG administration should be defined by prospective randomized controlled trials.
用于降低强度预处理(RIC)异基因造血干细胞移植(allo-HSCT)的抗胸腺细胞球蛋白(ATG)的适当剂量尚待确定。我们回顾性分析了接受无关或不匹配相关 RIC allo-HSCT 治疗血液系统恶性肿瘤的患者的结果,这些患者接受了 r-ATG(4.5mg/kg,141 例)与 R-ATG(6mg/kg,216 例)。R-ATG 组巨细胞病毒(P<0.001)和 EBV 血症(P=0.03)的发生率高于 r-ATG 组。r-ATG 和 R-ATG 组第 180 天急性移植物抗宿主病(aGVHD)Ⅱ-Ⅳ级的累积发生率分别为 59%和 44%(P=0.006),Ⅲ-Ⅳ级分别为 20%和 12%(P=0.029)。在调整疾病诊断的多变量模型中,aGVHD Ⅲ-Ⅳ级的风险无统计学意义(P=0.087)。r-ATG 和 R-ATG 组慢性移植物抗宿主病的累积发生率分别为 26%和 15%(P=0.10)。两组的复发率(P=0.24)、非复发死亡率(P=0.96)、无进展生存率(P=0.24)、总生存率(P=0.70)和无 GVHD 无复发生存率(P=0.24)无显著差异。在这项回顾性分析中,r-ATG 治疗组的 aGVHD 发生率高于 R-ATG 治疗组,但这并没有转化为临床结局的显著差异。鉴于 RIC allo-HSCT 越来越多地用于治疗恶性血液系统疾病,ATG 的正确剂量和给药方案应通过前瞻性随机对照试验来确定。