PTCy Versus ATG for GVHD Prophylaxis in Unrelated-donor Allo-HCT for AML in First Complete Remission With Cardiovascular Comorbidity: EBMT ALWP Matched-pair Analysis
Researchers from the European Society for Blood and Marrow Transplantation (EBMT) have found that using posttransplant cyclophosphamide (ptCy) for graft-versus-host disease (GVHD) prophylaxis in patients with cardiovascular comorbidities yields long-term outcomes comparable to those achieved with the more traditional antithymocyte globulin (ATG) approach. The study, published in Bone Marrow Transplantation in 2025, focused on patients with acute myeloid leukemia in first complete remission undergoing unrelated donor transplantation who had pre-existing conditions such as cardiac disease, arrhythmia, diabetes, obesity, or cerebrovascular disease. Because cyclophosphamide is known to carry a risk of cardiac toxicity, there has been concern that ptCy might be less safe in this vulnerable population. The main message of the study is that, despite these concerns, ptCy does not compromise survival or increase long-term mortality compared with ATG in this high-risk group.
Patients with cardiovascular comorbidities represent a particularly challenging group for allogeneic transplantation, as both the conditioning regimens and GVHD prophylaxis strategies can exacerbate cardiac risk. High-dose cyclophosphamide is associated with dose-dependent cardiotoxicity, and although ptCy has become a standard GVHD prophylaxis strategy because of its effectiveness, its safety in patients with pre-existing cardiovascular disease has remained uncertain. To address this, the investigators performed a large retrospective registry study using EBMT data from 2010 to 2022 and applied a rigorous propensity score matched-pair design to minimize bias. From an initial cohort of 1256 patients, they generated a balanced matched cohort of 432 patients, including 313 who received ATG and 119 who received ptCy, matched for age, performance status, donor type, conditioning intensity, cytogenetics, and other key variables.
At two years, outcomes were remarkably similar between the two groups. Overall survival was 67.5% (95% CI 61.0–73.2) with ATG and 68.6% (95% CI 56.7–77.8) with ptCy (HR 0.87, p=0.498). Leukemia-free survival was 60.4% versus 62.6% (p=0.424), relapse incidence was 22.1% versus 23.2% (p=0.976), and non-relapse mortality was 17.5% versus 14.1% (p=0.253) for ATG and ptCy, respectively. Rates of acute and chronic GVHD were also not significantly different. These data show that ptCy does not worsen survival or transplant-related mortality in patients with cardiovascular comorbidities and support its continued use in this growing patient population, while highlighting the need for prospective studies focused specifically on cardiac risk and early cardiac events.
Reference:
Vydra J, Ferhat AT, Kröger N, et al. Posttransplant cyclophosphamide versus antithymocyte globulin in patients with cardiovascular comorbidity undergoing allogeneic hematopoietic cell transplantation for acute myeloid leukaemia in first complete remission from unrelated donors: a retrospective matched-pair analysis from the ALWP of the EBMT. Bone Marrow Transplant. Published online December 3, 2025.