Reduction of Thymoglobuline from 7.5 mg/kg to 6 mg/kg in conditioning regimen extended time to the first cytomegalovirus detection after allogenic haematopoietic stem cell transplantation.

INTRODUCTION: The optimal dosage of anti-thymocyte globulin (ATG) may influence the outcome of patients after allogenic haematopoietic stem cell transplantation (HSCT). The aim of our study was to analyse human cytomegalovirus (CMV) infection data, incidence of graft-versus-host disease and other clinical endpoints comparing two patients cohorts that were administered two different Thymoglobuline Genzyme doses as part of the HSCT conditioning regimen. MATERIALS AND METHODS: Total of 65 adult patients received ATG (7.5 mg/kg or 6 mg/kg) as a part of the fludarabine/busulfan/ATG conditioning regimen. CMV DNAemia was monitored after HSCT using quantitative real-time PCR and preemptive treatment was started for viral loads above 1000 cp/ml. RESULTS: The mild ATG dose reduction extended the time to the first CMV detection after transplantation (28 days for 7.5 mg/kg dose vs. 40 days for 6 mg/kg dose, p = 0.04). But it did not reduce the incidence or influence first anti-CMV treatment onset, the initial viral load, peak viral load in whole blood or the antiviral therapy parameters (all p 0.18). No impact of ATG dose reduction on incidence of graft-versus-host-disease, relapse of underlying disease or mortality within first year after transplantation (all p 0.32) were observed. CONCLUSIONS: The reduced ATG dosages can allow lower toxicity of conditioning regimen while keeping the performance.

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).

Comparison of Different Rabbit Anti-Thymocyte Globulin Formulations in the Prophylaxis of Graft-Versus-Host Disease: A Systematic Review.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative treatment modality, frequently used for patients suffering from haematological malignancies. In the last two decades, there have been multiple randomised controlled trials (RCTs), review articles, and meta-analyses addressing the efficacy of rabbit anti-thymocyte globulin (r-ATG) as a graft-versus-host disease (GvHD) prophylaxis. Nevertheless, only a few aimed to compare the effectiveness of different r-ATG formulations. Since the last article we retrieved comparing different r-ATGs in GvHD prophylaxis dates back to 2017, we performed a systematic literature review of articles published since 2017 to this day, utilising PubMed, Scopus, Cochrane, and MEDLINE, with the main endpoints being prophylaxis of acute GvHD (aGvHD) and chronic GvHD (cGvHD). We subjected to scrutiny a total of five studies, of which four compared the differences between Thymoglobulin (ATG-T) and Grafalon (ATG-G), and one discussed the impact of ATG-T dose. Overall, cGvHD, aGvHD grades II-IV, TRM, OS, NRM, LFS, relapse, overall infections, and EBV reactivation do not seem to be affected by the type of utilised rATG. However, data on aGvHD grades III-IV, GRFS, moderate-severe cGvHD, and CMV reactivation is conflicting. Through our research, we sought to summarise the most recent findings concerning r-ATGs in allo-HCT, and provide insight into the differences between the targets and origin of various ATG formulations.