比较使用不同抗胸腺细胞球蛋白配方的配型匹配和不匹配非亲缘异体造血干细胞移植的疗效:代表波兰成人白血病小组的回顾性双中心经验

Cancers Pub Date : 2024-05-16 DOI:10.3390/cancers16101891
Ugo Giordano, Monika Mordak-Domagała, Małgorzata Sobczyk-Kruszelnicka, Sebastian Giebel, Lidia Gil, Krzysztof D. Dudek, Jarosław Dybko
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引用次数: 0

摘要

尽管过去几十年来免疫疗法取得了显著进步,但异体造血干细胞移植(allo-HCT)仍是一种前景广阔、可能治愈的治疗方式。只有少数研究对两种常用的兔抗胸腺细胞球蛋白(r-ATG)制剂进行了直接比较,特别是胸腺球蛋白(ATG-T,原Genzyme公司)和格拉法隆(ATG-G,原费森尤斯公司)。我们进行回顾性分析的主要目的是比较接受匹配或不匹配非亲属供者(MUD/MMUD)异体肝移植的成年患者在使用ATG-T或ATG-G预防移植物抗宿主病(GvHD)后的疗效。共纳入了87名在2012年至2022年期间接受过异体肝移植的患者。我们观察到,ATG-T 和 ATG-G 在急性移植物抗宿主病 (aGvHD) 的发生率上没有明显差异,无论其严重程度如何。相反,与 ATG-G 组相比,ATG-T 组的慢性移植物抗宿主病(cGvHD)发生率较低(7.5% 对 38.3%,P = 0.001)。多变量分析证实了ATG-G对cGvHD的负面影响(HR 8.12,95% CI 2.06-32.0,p = 0.003)。接受ATG-T治疗的患者巨细胞病毒(CMV)复发率更高(70% vs. 31.9%,p < 0.001),移植与CMV之间的间隔时间更短(<61天,77.8% vs. 33.3%,p = 0.008),CMV拷贝数中位数更高(1000 vs. 0,p = 0.004)。值得注意的是,尽管ATG-T队列中CMV再激活发生率较高,但与ATG-G队列相比,大多数患者无症状(85.7% vs. 43.8%,p = 0.005)。通过多变量分析,只有 aGvHD 对 CMV 再激活有影响(HR 0.18,95% CI 0.04-0.75,p = 0.019)。最后,我们观察到 ATG-T 和 ATG-G 的 5 年总生存率(OS)和 3 年无复发生存率(RFS)没有明显差异(分别为 32.0% vs. 40.3%,p = 0.423;66.7% vs. 60.4%,p = 0.544)。
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Comparing the Outcomes of Matched and Mismatched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation with Different Anti-Thymocyte Globulin Formulations: A Retrospective, Double-Centre Experience on Behalf of the Polish Adult Leukemia Group
Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies have performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations—specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients who had undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to the ATG-G group (7.5% vs. 38.3%, p = 0.001). The negative impact of ATG-G on cGvHD was confirmed by multivariate analysis (HR 8.12, 95% CI 2.06–32.0, p = 0.003). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p < 0.001), with a shorter time between transplant and CMV (<61 days, 77.8% vs. 33.3%, p = 0.008) and a higher median CMV copy number (1000 vs. 0, p = 0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p = 0.005). By multivariate analysis, only aGvHD had an influence on CMV reactivations (HR 0.18, 95% CI 0.04–0.75, p = 0.019). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year relapse-free survival (RFS) while comparing ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544, respectively).
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