Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

中文翻译：

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前瞻性、随机、双盲、抗 T 淋巴细胞球蛋白 III 期临床试验评估对接受 HLA 匹配的非相关清髓性造血细胞移植患者的慢性移植物抗宿主病无生存期的影响

目的 几项开放标签随机研究表明，用抗 T 淋巴细胞球蛋白（ATLG；以前的抗胸腺细胞球蛋白 - 费森尤斯）清除体内 T 细胞可减少慢性移植物抗宿主病 (cGVHD)，而不会影响生存。我们报告了一项前瞻性、双盲 III 期试验，以研究 ATLG（Neovii Biotech，列克星敦，马萨诸塞州）对无 cGVHD 生存率的影响。患者和方法 254 名 18 至 65 岁的急性白血病或骨髓增生异常综合征患者接受了清髓性 HLA 匹配无关造血细胞移植 (HCT)，以一对一的方式随机分配到安慰剂组（n = 128 安慰剂）或 ATLG (n = 126) 在 27 个部位进行治疗。除了他克莫司和甲氨蝶呤作为 GVHD 预防之外，患者在第 -3、-2、-1 天每天接受 ATLG 或安慰剂 20 mg/kg。主要研究终点是中重度无 cGVHD 生存。结果 尽管 ATLG 接受者的 2 至 4 级急性 GVHD（23% 对 40%；P = .004）和中重度 cGVHD（12% 对 33%；P < .001）减少，但中重度 cGVHD 没有差异发现 ATLG 和安慰剂之间的无 cGVHD 生存率（2 年估计：分别为 48% 和 44%；P = .47）。ATLG 的无进展生存期 (PFS) 和总生存期 (OS) 均较低（2 年估计值：分别为 47% 对 65% [ P = .04] 和 59% 对 74% [ P = .034]） . 多变量分析证实，ATLG 与较差的 PFS（风险比，1.55；95% CI，1.05 至 2.28；P = .026）和 OS（风险比，1.74；95% CI，1.12 至 2.71；P = .01）相关. 结论 在这项 ATLG 用于非相关清髓性 HCT 的前瞻性、随机、双盲试验中，加入 ATLG 并没有改善中重度无 cGVHD 的存活率。ATLG 的中重度 cGVHD 显着降低，但 PFS 和 OS 也较低。需要额外的分析来了解 ATLG 在 HCT 中的适当作用。