Very Low-Dose Anti-Thymocyte Globulin in HLA-Matched PBSCT – Results of a Phase II Study (JSCT-ATG 15) –

Background Allogeneic peripheral blood stem cell transplantation (PBSCT) is associated with an increased risk of severe acute graft-versus-host disease (GVHD) and chronic GVHD compared to bone marrow transplantation. Although several studies have shown that anti-thymocyte globulin (ATG) reduces severe acute and chronic GVHD in PBSCT following myeloablative conditioning (MAC), an optimal of ATG remains to be determined. Methods We conducted a multicenter phase II study to investigate safety and efficacy of very low-dose ATG in patients undergoing HLA-matched PBSCT after MAC (UMIN000018645). A total of 2mg/kg ATG (Thymoglobulin; 1mg/kg, days -2, -1) was given in combination with calcineurin inhibitor and methotrexate for prophylaxis of GVHD. The primary endpoint was grade III to IV GVHD at day100. Results From November 2015 to October 2018, a total of 77 patients were enrolled and 72 patients with a median age of 46.5 years were eligible for analysis. These included acute myeloid leukemia (n = 36), acute lymphoblastic leukemia (n = 19), myelodysplastic syndrome (n = 8), lymphoma (n = 5), and others (n = 4). All patients achieved neutrophil engraftment with a median of 13 days. The primary endpoint, cumulative incidence of grades III to IV acute GVHD at day100 was 1.4% (95% CI, 0.1 to 6.7%), which was greatly less than our pre-defined statistical threshold value in this study (18%), and the incidence of chronic GVHD at 1 year was also significantly low (all-grade; 15.3%, moderate to severe; 5.6%). Non-relapse mortality, relapse, overall survival, progression-free survival, and GVHD-free, relapse-free survival rate at 1 year were 4.2%, 20.8%, 84.7%, 75.0%, and 69.4%, respectively. Conclusion Our study demonstrated that GVHD prophylaxis using very low-dose ATG in HLA-matched PBSCT is feasible and effective for significant prevention of severe acute and chronic GVHD.