Allogeneic hematopoietic cell transplantation (allo-HCT) offers a potential cure for high-risk hematological malignancy; however, long-term survivors experience increased cardiovascular morbidity and mortality. It is unclear how allo-HCT impacts cardiovascular function in the short-term. Thus, this 3-month prospective study sought to evaluate the short-term cardiovascular impact of allo-HCT in hematological cancer patients, compared to an age-matched non-cancer control group.Before and ~3-months following allo-HCT, 17 hematological cancer patients (45 ± 18 years) underwent cardiopulmonary exercise testing to quantify peak oxygen uptake (VOpeak)-a measure of integrative cardiovascular function. Then, to determine the degree to which changes in VOpeak are mediated by cardiac vs. non-cardiac factors, participants underwent exercise cardiac MRI (cardiac reserve), resting echocardiography (left-ventricular ejection fraction [LVEF], global longitudinal strain [GLS]), dual-energy x-ray absorptiometry (lean [LM] and fat mass [FM]), blood pressure (BP) assessment, hemoglobin sampling, and arteriovenous oxygen difference (a-vOdiff) estimation the Fick equation. Twelve controls (43 ± 13 years) underwent identical testing at equivalent baseline and 3-month time intervals.2ignificant group-by-time interactions were observed for absolute VOpeak ( = 0.006), bodyweight-indexed VOpeak ( = 0.015), LM ( = 0.001) and cardiac reserve ( = 0.019), which were driven by 26, 24, 6, and 26% reductions in the allo-HCT group (all ≤ 0.001), respectively, as no significant changes were observed in the age-matched control group. No significant group-by-time interactions were observed for LVEF, GLS, FM, hemoglobin, BP or a-vOdiff, though a-vOdiff declined 12% in allo-HCT ( = 0.028).SIn summary, allo-HCT severely impairs VOpeak, reflecting central and peripheral dysfunction. These results indicate allo-HCT rapidly accelerates cardiovascular aging and reinforces the need for early preventive cardiovascular intervention in this high-risk group.2