Coronary Artery Calcification as a Predictor of Survival in Patients Receiving Post-transplant Cyclophosphamide for GVHD Prophylaxis

Abstract

Post-transplant Cyclophosphamide (PTCy) is becoming the new standard of care for graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT). High-dose cyclophosphamide has been associated with cardiac dysfunction through multiple mechanisms. Assess if patients with evidence of coronary artery calcification (CAC) are at higher risk for non-relapse mortality (NRM) and inferior survival after receiving PTCy for GVHD prophylaxis. We retrospectively reviewed patients with hematologic diseases undergoing alloHCT using PTCy for GVHD prophylaxis in the Mayo Clinic Enterprise from 2018 to 2022. Patients with non-contrast CT imaging for review for CAC within 1 year (yr) of alloHCT were included in this study, with imaging analyzed by a blinded independent reviewer. Of 204 patients who received PTCy for GVHD prophylaxis, 144 (70.5%) had available CT imaging available for CAC review. Seventy-three (50.7%) patients were positive for CAC (+) and 71 (49.3%) were negative for CAC (-). Compared to CAC-, CAC+ patients were older (64 versus 45 years, P < .001) and more likely to have known coronary artery disease (CAD) before transplant (16.4% versus 1.4%, P = .004), but had comparable HCT-CI (P=0.17). NRM was higher among patients with CAC+ compared to CAC- at 1 and 2-yr (26.5% versus 8.9%, P = .008), (28.0% versus 8.9%, P = .005), respectively. Univariate competing risk analysis showed that CAC was significantly associated with 2-yr NRM (HR 3.41, 95% CI 1.36-8.54, P = .009) and inferior post-alloHCT survival (2-yr OS rate 51.6% versus 72.3%, P = .01). Multivariate analysis (MVA) confirmed that CAC+ was associated with 2-yr NRM (HR 4.37, 95% CI 1.71-11.18, P = .002). While CAC+ did not impact OS in the whole cohort, among elderly patients age ≥60 and without a history of CAD, MVA confirmed that CAC+ was associated with an inferior 2-yr OS (HR 3.67, 95% CI 1.007-13.38, P = .049) and higher NRM (35.5% versus 0%, P = .006). Coronary artery calcification is readily assessable in imaging studies during pretransplant evaluation. Among patients receiving PTCy, CAC was associated with a higher NRM. CAC+ was associated with inferior OS, particularly in elderly patients without a history of coronary artery disease.

Keywords: Allogeneic transplant; Coronary artery calcium; NRM; Post-transplant cyclophosphamide.