Effect Analysis of 33 Patients with Corticosteroids Resistant Grade III/IV Acute Liver Graft-Versus-Host Disease Treated with Sequential Low-Dose Cyclophosphamide and Anti-Thymocyte Globulin Following Plasma Exchange

Background Acute graft-versus-host disease (aGVHD) represents a significant complication and leading cause of mortality in allo-HSCT. The response rate to corticosteroids is approximately 50%, with poor long-term survival observed in individuals with steroid-resistant (SR) aGVHD. Plasma exchange stands as the primary treatment for patients experiencing acute liver failure. Cyclophosphamide and anti-thymocyte globulin (ATG) function to inhibit lymphocyte activity in vivo. Currently, there are no clinical studies validating the efficacy of plasma exchange followed by low-dose cyclophosphamide and ATG for the treatment of liver Grade III/IV SR aGVHD. Methods A retrospective analysis was performed on 33 hematological patients who developed liver grade III/IV aGVHD after allo-HSCT in Henan Cancer Hospital from October 2020 to March 2024 and were treated with sequential low-dose cyclophosphamide and anti-thymocyte globulin after plasma exchange. Cyclophosphamide dose: 400 mg/ time for adults and children weighing ≥35 kg, 200mg/ time for children weighing < 35 kg, immediately after the end of plasma exchange. Anti-thymocyte globulin dose: adults and children weighing ≥35 kg 50mg/ time, children weighing < 35 kg 25mg/ time, immediately after the end of cyclophosphamide. Efficacy was evaluated 28 days after the first plasmapheresis. Results Among the 33 patients, 19 were males (57.6%) and 14 were females (42.4%). The median age was 29 (5-57) years.There were 9 cases (27.3%) of typical aGVHD and 24 cases (72.7%) of delayed aGVHD. There were 27 patients (81.8%) with grade III liver aGVHD and 6 patients (18.2%) with grade IV liver aGVHD. 15 patients (45.5%) achieved complete response (CR), 9 patients (27.3%) achieved partial response (PR), and 9 patients (27.3%) achieved no response (NR). The overall response rate (ORR) was 72.7% (24/33). After a median follow-up of 100 (6-1344) days, the overall survival (OS) rate of the 33 patients at 6 months after treatment was 42.8% (95%CI 25.4%-60.2%), and the OS rate at 1 year after treatment was 35.9% (95%CI 18.8%-53.0%). The OS rates of CR group, PR group and NR group at 6 months after treatment were 69.2% (95% CI 36.1%-86.3%) ,44.4% and 0, respectively. One year after treatment, the OS rates were 52.7% (95%CI 25.1%-80.3%), 44.4% (95%CI 11.9%-76.9%), 0, respectively, and the difference was statistically significant among the three groups (χ2 = 4.474, P < 0.001). Conclusions Sequential low-dose cyclophosphamide and anti-thymocyte globulin after plasma exchange may be an effective treatment for patients with corticosteroids resistant liver grade III/IV aGVHD.