外周血单倍体造血干细胞移植中抗胸腺细胞球蛋白联合移植后环磷酰胺预防移植物抗宿主病的应用经验。
Experience Using Anti-Thymocyte Globulin With Post-Transplantation Cyclophosphamide for Graft-Versus-Host Disease Prophylaxis in Peripheral Blood Haploidentical Stem Cell Transplantation.
机构信息
Section of Medical Oncology and Hematology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Bone Marrow Transplantation Unit, Department of Hematology, Hospital Clínic of Barcelona, IDIBAPS, Barcelona, Spain.
Department of Biostatistics, Princes Margaret Cancer Centre, University Health Network. Toronto, Ontario, Canada.
出版信息
Transplant Cell Ther. 2021 May;27(5):428.e1-428.e9. doi: 10.1016/j.jtct.2021.02.007. Epub 2021 Feb 13.
Haploidentical hematopoietic cell transplantation (HaploHCT) is an alternative treatment option for patients without a suitable 10/10 HLA matched donor. We share an updated experience at our center of using in vivo dual T-cell depletion with anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) in peripheral blood haploHCT and report the impact of reducing the dose of ATG from 4.5 mg/kg to 2 mg/kg on post-transplantation complications and outcomes. Ninety-five consecutive adults underwent haploHCT at our center between August 2016 and February 2020, all of whom were included in the study. Nine (9.5%) patients received myeloablative conditioning, and 86 (90.5%) patients underwent reduced-intensity haploHCT. All patients received thymoglobulin, PTCy and cyclosporine (CsA) for graft-versus-host disease (GVHD) prophylaxis: Sixty (63.2%) patients received 4.5 mg/kg, and 35 (36.8%) patients received 2 mg/kg of ATG. Clinical information was collected retrospectively and updated in June 2020. The median age was 57 (18-73), and acute myeloid leukemia was the most prevalent diagnosis (58.9%). The day 100 cumulative incidence of grade II-IV and grade III-IV aGVHD, and 1-year moderate/severe cGVHD were 22.3%, 11.1%, and 20.2%, respectively. Those patients who received 2 mg/kg of ATG had higher incidence of grade III-IV aGVHD (23.9% vs 3.5%, P = .006) and comparable moderate/severe cGVHD (1-year 20.6% vs 19.8%, P = .824) than those patients who received 4.5 mg/kg. Overall, the 18-month overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM) were 43.8%, 38.4%, and 40.2%, respectively. The reduction of the ATG dose did not have a significant impact in OS (hazard ratio [HR] 1.06, P = .847), RFS (HR 0.984, P = .955), and in NRM (HR 1.38; P = .348). The reduction of the ATG resulted in a negative impact on aGVHD without conferring any benefit in OS, RFS, and NRM. Consequently, the ATG dose used at our institution in combination with PTCy and CsA for haploHCT continues to be 4.5 mg/kg.
单倍体造血细胞移植（haploHCT）是一种替代治疗方案，适用于没有合适的 10/10 HLA 匹配供体的患者。我们在中心分享了使用抗胸腺细胞球蛋白（ATG）和移植后环磷酰胺（PTCy）进行外周血单倍体 HaploHCT 的最新经验，并报告了将 ATG 剂量从 4.5mg/kg 降低至 2mg/kg 对移植后并发症和结果的影响。95 例连续成年患者于 2016 年 8 月至 2020 年 2 月在我们中心接受单倍体 HaploHCT，所有患者均纳入研究。9（9.5%）例患者接受了清髓性预处理，86（90.5%）例患者接受了强度降低的单倍体 HaploHCT。所有患者均接受了他莫昔芬、PTCy 和环孢素（CsA）预防移植物抗宿主病（GVHD）：60（63.2%）例患者接受了 4.5mg/kg，35（36.8%）例患者接受了 2mg/kg 的 ATG。临床信息回顾性收集并于 2020 年 6 月更新。中位年龄为 57（18-73）岁，急性髓细胞白血病是最常见的诊断（58.9%）。第 100 天的 II-IV 级和 III-IV 级急性移植物抗宿主病（aGVHD）累积发生率，以及 1 年中/重度慢性移植物抗宿主病（cGVHD）发生率分别为 22.3%、11.1%和 20.2%。接受 2mg/kg ATG 的患者 III-IV 级 aGVHD 发生率更高（23.9% vs 3.5%，P=0.006），但 1 年中/重度 cGVHD 发生率相似（1 年 20.6% vs 19.8%，P=0.824）。总体而言，18 个月的总生存率（OS）、无复发生存率（RFS）和非复发死亡率（NRM）分别为 43.8%、38.4%和 40.2%。ATG 剂量的降低对 OS（风险比 [HR] 1.06，P=0.847）、RFS（HR 0.984，P=0.955）和 NRM（HR 1.38；P=0.348）均无显著影响。ATG 剂量的降低对 aGVHD 有负面影响，但在 OS、RFS 和 NRM 方面没有任何益处。因此，我们机构在单倍体 HaploHCT 中继续使用 4.5mg/kg 的 ATG 联合 PTCy 和 CsA。
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