Favorable Outcomes with Low Dose Anti Thymocyte Globulin Based Graft Versus Host Disease Prophylaxis after Mismatched Unrelated Donor Allogenic Hematopoietic Cell Transplantation

Introduction Anti-thymocyte globulin (ATG) based Graft versus Host disease (GVHD) prophylaxis is widely used for unrelated donor allogeneic hematopoietic cell transplantation (HCT) although optimal dose remains unclear. Registry-based and single-center retrospective analyses have suggested superior outcomes with PTCy-based GVHD prophylaxis regimens when compared to ATG-based in mismatched unrelated donor (MMUD) allogeneic HCT. However, these studies used doses of ATG ≥ 5mg/kg. Outcomes following MMUD allogeneic HCT with lower dose ATG-based GVHD prophylaxis regimens have not been extensively studied. Thus, we analyzed outcomes of HLA 9/10 MMUD allogeneic HCTs using lower dose ATG-based regimens at our centre. Methods All adult patients undergoing standard of care allogeneic HCT at The Ottawa Hospital from January 2015 to December 2022 were included. Data regarding demographics, HLA mismatched allele, conditioning regimen, dose of ATG, time to engraftment, and rates of acute and chronic GVHD were collected. Primary outcomes were overall survival (OS) and secondary outcomes included GVHD-free relapse-free survival (GRFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). Survival outcomes were analyzed using Kaplan-Meier analysis. Predictors of survival were identified using the Cox-proportional hazards regression model. Results Seventy-seven (n=77) patients (Males 62.3% (n=48); Median (range) age 50 (18-70) years) underwent allogeneic HCT from MMUD. Most frequently mismatched locus was HLA A in 37.7% (n= 29) followed by HLA B in 14.3% (n=11). Myeloablative conditioning regimen was received by 76.6% (n=59) while reduced intensity regimens were used in 23.4% (n=18) patients. Rabbit ATG was used in all patients with the majority (81%; n=63) receiving 2.5mg/kg and the remaining 18.2% (n=14) receiving 4.5mg/kg of ATG. Grade II-IV acute GVHD occurred in 24.7% (n=19) while chronic GVHD occurred in 32.5% (n= 25) patients. After a median follow-up of 21 months, relapse occurred in 28.6% of patients. Two-year OS(Fig 1) and GRFS (Fig 2) were 60.6% and 45.3% respectively. Dose of ATG (2.5 mg/kg vs 4.5 mg/kg) was not a predictor of outcomes in either univariate and multivariate analyses. When compared to published single-center and registry-based studies using ATG doses ≥5 mg/kg, GVHD prophylaxis using lower dose ATG seems to provide improved outcomes in patients undergoing MMUD allogeneic HCT (Table 1). Conclusion Our findings suggest that lower dose ATG-based GVHD prophylaxis regimens may provide outcomes comparable to PTCy-based regimens in patients undergoing MMUD allogeneic HCT. Further studies are needed to directly compare lower dose ATG to PTCy-based regimens to determine ideal GVHD prophylaxis for these patients.