Coronary Artery Calcium As a Predictor of Non-Relapse Mortality and Overall Survival in Patients Undergoing Post-Transplant Cyclophosphamide As Gvhd Prophylaxis

Introduction Post-transplant Cyclophosphamide (PTCy) is now the standard of care for graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplant (alloHCT). High dose cyclophosphamide, as used in PTCy, is associated with cardiac dysfunction through direct toxicity to myocytes and cardiac endothelium. We hypothesize that patients with cardiac risk factors pre-alloHCT, such as presence of coronary artery calcium (CAC), are at higher risk for non-relapse mortality (NRM) and inferior survival after receiving PTCy for GVHD prophylaxis. Methods We retrospectively reviewed patients with hematologic diseases who underwent alloHCT and received PTCy for GVHD prophylaxis in the Mayo Clinic Enterprise from 2018 to 2022. Patients who had non-contrast CT imaging for CAC within 1 year of alloHCT were included in this study. Due to the association of age with CAC, age>60 was included in the multivariate analysis (MVA) for both NRM and overall survival (OS). MVA included CAC+, and other factors known to be associated with NRM such as age > 60 years at alloHCT, high HCT-CI and myeloablative conditioning. MVA for 2-year OS included age at alloHCT, haploidentical transplant, high/very high DRI and CAC+. Results A total of 204 patients received PT-Cy for GVHD prophylaxis, with 145 patients having available CAC imaging. Seventy-four (51%) patients were positive for CAC (+) and 71 (49%) were negative for CAC (-). As expected, compared to CAC- group, CAC+ patients were significantly older in age (median 64 vs. 45 years, P <0.001), and were more likely to have CAD before transplant (16.2% vs. 1.4%, P=0.008). However, both groups had comparable HCT-CI (P=0.54). Median follow-up after alloHCT was 2 years (95% CI 1.75-2.32 years). NRM at 2-years after alloHCT was significantly higher in CAC+ patients (26.7% vs. 10.4%, P=0.017, Figure 1). OS at 2 years post-alloHCT was lower in CAC+ patients (OS rate 49.1% vs. 75.7%, P=0.002, Figure 2). Univariate competing risk analysis showed CAC to be significantly associated with 2-year NRM (HR 2.74, 95% CI 1.15-6.54, P = 0.02). MVA confirmed CAC+ to be significantly associated with 2-year NRM (HR 2.53, 95% CI 1.04-6.14, P = 0.04). MVA confirmed CAC+ was associated with inferior survival (HR 2.4, 95% CI 1.14-5.06, P = 0.02).Twenty-six (17.9%) patients had NRM by 2 years after transplant with acute respiratory distress syndrome (ARDS)/multiorgan failure (MOF) [10 of 26 patients, 61.5%] as the most common cause of NRM (Table 1). Only 20% CAC+ patients had a positive cardiac HCT-CI, with two having NRM compared to 17 with negative cardiac HCT-CI. Conclusion Coronary artery calcium is readily assessable in imaging studies during pretransplant evaluation, is a surrogate of atherosclerotic burden, and may suggest chronic endothelial injury. Presence of CAC may predict higher risk of NRM and inferior OS in patients receiving PTCy.