Giordano Ugo, Mordak-Domagała Monika, Sobczyk-Kruszelnicka Małgorzata, Giebel Sebastian, Gil Lidia, Dudek Krzysztof D, Dybko Jarosław
Department and Clinic of Endocrinology, Diabetes and Isotope Therapy, 50-367 Wroclaw, Poland.
Lower Silesian Center of Oncology, Pulmonology and Hematology, 53-439 Wroclaw, Poland.
Cancers (Basel). 2024 May 16;16(10):1891. doi: 10.3390/cancers16101891.
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%, = 0.001). The negative impact of ATG-G on cGvHD was confirmed by multivariate analysis (HR 8.12, 95% CI 2.06-32.0, = 0.003). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, < 0.001), with a shorter time between transplant and CMV (<61 days, 77.8% vs. 33.3%, = 0.008) and a higher median CMV copy number (1000 vs. 0, = 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%, = 0.005). By multivariate analysis, only aGvHD had an influence on CMV reactivations (HR 0.18, 95% CI 0.04-0.75, = 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%, = 0.423; 66.7% vs. 60.4%, = 0.544, respectively).
尽管在过去几十年中免疫疗法取得了显著进展，但异基因造血干细胞移植（allo-HCT）仍然是一种有前景的、可能治愈的治疗方式。只有少数研究对两种常见的兔抗胸腺细胞球蛋白（r-ATG）制剂进行了直接比较，即Thymoglobuline（ATG-T，原Genzyme公司生产）和Grafalon（ATG-G，原费森尤斯公司生产）。我们回顾性分析的主要目的是比较接受匹配或不匹配无关供体（MUD/MMUD）allo-HCT的成年患者的结局，这些患者采用基于ATG-T或ATG-G的移植物抗宿主病（GvHD）预防方案。纳入了2012年至2022年间接受allo-HCT的87例患者。我们观察到，无论急性移植物抗宿主病（aGvHD）的严重程度如何，ATG-T和ATG-G在aGvHD的发生方面没有显著差异。相反，与ATG-G组相比，ATG-T组慢性移植物抗宿主病（cGvHD）的发生率更低（7.5%对38.3%，P = 0.001）。多因素分析证实了ATG-G对cGvHD的负面影响（风险比8.12，95%置信区间2.06 - 32.0，P = 0.003）。接受ATG-T治疗的患者巨细胞病毒（CMV）再激活的发生率更高（70%对31.9%，P < 0.001），移植与CMV再激活之间的时间更短（<61天，77.8%对33.3%，P = 0.008），CMV拷贝数中位数更高（1000对0，P = 0.004）。值得注意的是，尽管ATG-T队列中CMV再激活的发生率更高，但与ATG-G相比，大多数患者无症状（85.7%对43.8%，P = 0.005）。通过多因素分析，只有aGvHD对CMV再激活有影响（风险比0.18，95%置信区间0.04 - 0.75，P = 0.019）。最后，在比较ATG-T和ATG-G时，我们观察到5年总生存率（OS）和3年无复发生存率（RFS）没有显著差异（分别为32.0%对40.3%，P = 0.423；66.7%对60.4%，P = 0.544）。
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