抗胸腺细胞球蛋白用于血液系统恶性肿瘤患者的同胞供者移植：一项多中心、开放标签、随机对照研究。
Antithymocyte Globulin for Matched Sibling Donor Transplantation in Patients With Hematologic Malignancies: A Multicenter, Open-Label, Randomized Controlled Study.
机构信息
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, and Peking-Tsinghua Center for Life Sciences, Beijing, China.
Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
出版信息
J Clin Oncol. 2020 Oct 10;38(29):3367-3376. doi: 10.1200/JCO.20.00150. Epub 2020 Jul 10.
PURPOSE
The role of antithymocyte globulin (ATG) in preventing acute graft-versus-host disease (aGVHD) after HLA-matched sibling donor transplantation (MSDT) is still controversial.
PATIENTS AND METHODS
We performed a prospective, multicenter, open-label, randomized controlled trial (RCT) across 23 transplantation centers in China. Patients ages 40-60 years with standard-risk hematologic malignancies with an HLA-matched sibling donor were randomly assigned to an ATG group (4.5 mg/kg thymoglobulin plus cyclosporine [CsA], methotrexate [MTX], and mycophenolate mofetil [MMF]) and a control group (CsA, MTX, and MMF). The primary end point of this study was grade 2-4 aGVHD on day 100.
RESULTS
From November 2013 to April 2018, 263 patients were enrolled. The cumulative incidence rate of grade 2-4 aGVHD was significantly reduced in the ATG group (13.7%; 95% CI, 13.5% to 13.9%) compared with the control group (27.0%; 95% CI, 26.7% to 27.3%; = .007). The ATG group had significantly lower incidences of 2-year overall chronic GVHD (27.9% [95% CI, 27.6% to 28.2%] 52.5% [95% CI, 52.1% to 52.9%]; < .001) and 2-year extensive chronic GVHD (8.5% [95% CI, 8.4% to 8.6%] 23.2% [95% CI, 22.9% to 23.5%]; = .029) than the control group. There were no differences between the ATG and control groups with regard to cytomegalovirus reactivation, Epstein-Barr virus reactivation, 3-year nonrelapse mortality (NRM), 3-year cumulative incidence of relapse (CIR), 3-year overall survival, or 3-year leukemia-free survival. Three-year GVHD relapse-free survival was significantly improved in the ATG group (38.7%; 95% CI, 29.9% to 47.5%) compared with the control group (24.5%; 95% CI, 16.9% to 32.1%; = .003).
CONCLUSION
Our study is the first prospective RCT in our knowledge to demonstrate that ATG can effectively decrease the incidence of aGVHD after MSDT in the CsA era without affecting the CIR or NRM.
目的
抗胸腺细胞球蛋白（ATG）在预防 HLA 匹配的同胞供体移植（MSDT）后急性移植物抗宿主病（aGVHD）中的作用仍存在争议。
患者和方法
我们在中国 23 个移植中心进行了一项前瞻性、多中心、开放标签、随机对照试验（RCT）。年龄在 40-60 岁、患有标准风险血液系统恶性肿瘤且有 HLA 匹配同胞供体的患者被随机分配到 ATG 组（4.5mg/kg 胸腺球蛋白加环孢素[CsA]、甲氨蝶呤[MTX]和霉酚酸酯[MMF]）和对照组（CsA、MTX 和 MMF）。本研究的主要终点是第 100 天 2-4 级 aGVHD。
结果
从 2013 年 11 月至 2018 年 4 月，共纳入 263 例患者。与对照组（27.0% [95%CI，26.7%至 27.3%]； =.007）相比，ATG 组（13.7% [95%CI，13.5%至 13.9%]）2-4 级 aGVHD 的累积发生率显著降低。ATG 组 2 年总慢性移植物抗宿主病（GVHD）的发生率（27.9% [95%CI，27.6%至 28.2%] 52.5% [95%CI，52.1%至 52.9%]； <.001）和 2 年广泛慢性 GVHD（8.5% [95%CI，8.4%至 8.6%] 23.2% [95%CI，22.9%至 23.5%]； =.029）明显低于对照组。ATG 组与对照组在巨细胞病毒再激活、Epstein-Barr 病毒再激活、3 年非复发死亡率（NRM）、3 年累积复发率（CIR）、3 年总生存率或 3 年无白血病生存率方面无差异。与对照组（24.5% [95%CI，16.9%至 32.1%]； =.003）相比，ATG 组 3 年 GVHD 无复发生存率（38.7% [95%CI，29.9%至 47.5%]）显著提高。
结论
本研究是我们所知的首个前瞻性 RCT，证明在 CsA 时代，ATG 可有效降低 MSDT 后 aGVHD 的发生率，而不影响 CIR 或 NRM。
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