GVHD Prophylaxis With ATG and PTCy Versus PTCy-Based Regimens in Haploidentical Stem Cell Transplantation: A CTTC
Alejandro Garcia-Horton1, Brittany Salter1, Kristjan Paulson2
1Department of Oncology, Juravinski Hospital and Cancer Centre, McMaster University, Hamilton, ON, Canada.
Background:
Graft-versus-host disease (GVHD) remains a barrier to long-term success of haploidentical donor (HID) allogeneic hematopoietic cell transplantation (HCT). Post-transplant cyclophosphamide (PTCy) is considered standard prophylaxis, while the addition of anti-thymocyte globulin (ATG) has been utilized by some centres to further reduce GVHD.
Methods:
We conducted a retrospective, multicenter analysis using the Cell Therapy Transplant Canada (CTTC) registry to compare outcomes of ATG-PTCy versus PTCy-only GVHD prophylaxis among adults undergoing HID HCT for hematologic malignancies between 2016 and 2023. Endpoints included overall survival (OS), acute GVHD (aGVHD), chronic GVHD (cGVHD), GVHD-free/relapse-free survival (GRFS), relapse, and non-relapse mortality (NRM). Multivariable Cox regression and propensity score matched analyses accounted for patient-, disease-, and transplant-related factors.
Results:
Of 385 patients (148 ATG-PTCy, 237 PTCy) were included. Two-year OS and cumulative incidence of relapse (CIR) were similar between groups: 61% vs. 64% (p = .29) and 19.6% vs. 19.4% (p = 1.0). ATG-PTCy significantly reduced moderate-severe cGVHD: 11% vs. 30% (HR: 2.28, p = .001), but two-year NRM was higher with ATG-PTCy: 27% vs. 18% (p = .04), likely related to increased infection risk. Propensity-score matched analysis revealed no difference in OS (p = .46), but lower moderate-severe cGVHD rates (p = .002), higher relapse (p=0.009) and similar NRM (p = .62) with ATG-PTCy. In AML patients (n = 196), relapse remained similar, but OS favored PTCy (OS at 2-year 71% vs. 50%, p < .001) due to excess NRM with ATG-PTCy. Multivariable analyses confirmed age and comorbidity burden as predictors of worse OS, while prophylaxis regimen independently influenced cGVHD risk.
Conclusion:
In this registry analysis, ATG-PTCy significantly reduced the incidence of moderate-to-severe cGVHD compared with PTCy alone; however, this benefit was offset by higher risks of relapse and NRM, ultimately yielding similar survival between the two regimens. These findings highlight the need for individualized prophylaxis strategies balancing GVHD prevention with infection-related risks.
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