ATG in HLA-matched, peripheral blood, hematopoietic cell transplantation in acute myeloid leukemia and myelodysplastic syndrome: a secondary analysis of a CIBMTR database
Adults over 40 years drawn from the CIBMTR database, undergoing first peripheral blood stem cell transplant from matched related donor or matched unrelated donor for acute myeloid leukemia or myelodysplastic syndrome with or without ATG (n=4320)
Intervention
Received Anti-T cell globulin (ATG) prophylaxis (n=1007)
Comparison
Received no ATG prophylaxis (n=3313)
Outcome
Overall survival was not different with ATG (HR = 1.09, 95CI 1.00-1.19) compared with no ATG. Relapse rate was higher with ATG (HR = 1.29, 95CI 1.17-1.43) and non-relapse mortality was lower with ATG (HR = 0.84, 95CI 0.72-0.98). Grades II-IV acute GVHD was significantly lower with ATG (HR = 0.77, 95CI 0.69-0.87) but not grades III-IV acute GVHD (HR = 0.85, 95CI 0.69-1.04). Both chronic GVHD (HR = 0.54, 95CI 0.48-0.60) and moderate/severe chronic GVHD (HR = 0.45, 95CI 0.38-0.52) were lower with ATG. Relapse rate was higher in those who received reduced-intensity (RIC) or non-myeloablative (NMA) conditioning regimens and ATG, compared with myeloablative conditioning with or without ATG or RIC without ATG. Overall survival was also poorer with ATG and RIC or NMA conditioning regimens.
Abstract
BACKGROUND Peripheral blood stem cells (PBSC) are the preferred grafts for hematopoietic cell transplantation (HCT), according to the CIBMTR. Donor recovery is faster with PBSC harvest, but PBSC is associated with higher chronic graft-versus-host disease (GVHD) and poorer quality of life. Anti-T cell globulin (ATG) is polyclonal IgG from rabbits or horses immunized with human thymocytes or a human T-cell
line which may reduce graft-versus-host disease in HCT and improve outcomes. OBJECTIVE The objective of this study was to analyze the impact of ATG in HLA-matched Related (MRD) and matched (HLA 8/8) unrelated donor (MUD) HCT. STUDY DESIGN We used a freely available CIBMTR database published online for secondary analyses. The database included patients ≥ 40 y/o who have undergone their first PBSC MRD or MUD HCT for acute myeloid leukemia or myelodysplastic syndrome with or without ATG between 2008 and 2017. Patients who received posttransplant cyclophosphamide or alemtuzumab were excluded. RESULTS Overall survival was not different with ATG (HR = 1.09, 95CI 1.00-1.19, p = 0.06) compared with no ATG. Relapse rate was higher with ATG (HR = 1.29, 95CI 1.17-1.43, p < 0.001) and NRM was lower with ATG (HR = 0.84, 95CI 0.72-0.98, p = 0.03). Grades II-IV acute GVHD was significantly lower with ATG (HR = 0.77, 95CI 0.69-0.87, p < 0.001) but not grades III-IV acute GVHD (HR = 0.85, 95CI 0.69-1.04, p = 0.11). Both chronic GVHD (HR = 0.54, 95CI 0.48-0.60, p < 0.001) and moderate/severe chronic GVHD (HR = 0.45, 95CI 0.38-0.52, p < 0.001) were lower with ATG. There was an interaction between ATG and conditioning regimen for relapse rate and overall survival. Relapse rate was higher in those who received reduced-intensity (RIC) or non-myeloablative (NMA) conditioning regimens and ATG, compared with MAC ± ATG or RIC without ATG (interaction test, p = 0.003). Overall survival was also poorer with ATG and RIC or NMA conditioning regimens (interaction test, p = 0.03). CONCLUSION Our results show that ATG can mitigate the more severe forms of chronic GVHD without impairing overall survival in HLA-matched HCT with PBSC grafts and myeloablative conditioning regimen. ATG should be standard in this population.
PICO Summary