Targeting exercise and sedentary behavior for the prevention of allogeneic stem cell transplant-related cardiovascular dysfunction: The ALLO-Active trial.
Authors: Hayley T. Dillon, Erin Howden, Nicholas J. Saner, Tegan Ilsley, David S. Kliman, Stephen J. Foulkes, Christian J. Brakenridge, Andrew Spencer, Sharon J. Avery, Piet Claus, David W. Dunstan, Robin M. Daly, Steve F. Fraser, Neville Owen, Brigid M. Lynch, Bronwyn A. Kingwell, Andre La Gerche
Journal: Journal of Clinical Oncology (2024)

12018 Targeting Exercise and Sedentary Behavior to Prevent Allogeneic Stem Cell Transplant-Related Cardiovascular Dysfunction: The ALLO-Active Trial Background: Allogeneic stem cell transplantation (allo-SCT) is a potentially life-saving therapy for hematological malignancy, however, quality of life and longevity post allo-SCT are hampered by exercise intolerance, cardiac dysfunction, and cardiovascular mortality. This randomized controlled trial evaluated the efficacy of a novel multi-component activity program on cardiorespiratory fitness (peak oxygen uptake [VO 2peak ]) and cardiac function in adults undergoing allo-SCT. Methods: Sixty-two hematological malignancy patients scheduled for allo-SCT were randomized to a 4-month multi-component Activity program (n = 30) designed to increase aerobic and resistance exercise (3-day.week -1 ) and reduce sedentary time (≥30-min.day -1 ), or to usual care ( UC, n = 32). The Activity program was delivered over two distinct phases: ‘Inpatient’, which commenced upon admission for allo-SCT and continued until discharge (~4 weeks), and ‘Outpatient’,which commenced at discharge and continued for 12-weeks. Physiological assessments were conducted pre-admission, and 12-weeks post-discharge (4-months from baseline) and included: (1) cardiopulmonary exercise testing to quantify VO 2peak , (2) exercise cardiac magnetic resonance imaging to determine peak cardiac output and stroke volume index (COI peak and SVI peak ), (3) standard of care resting echocardiography-derived left ventricular ejection fraction and global longitudinal strain, and (4) cardiac biochemistry (troponin, B-type natriuretic peptide). Results: Fifty-two patients (84%) completed follow-up (25 Activity; 27 UC), and median (IQR) intervention adherence was 73% (50-81). Activity preserved VO 2peak (-0.9ml.kg -1 .min -1 [95%CI -2.5, 0.8]) which showed a marked decline with UC (-3.4ml.kg -1 .min -1 [95%CI -4.9, -1.8]; interaction, p= 0.029). Activity also showed significant benefits on exercise cardiac function, as shown by a preservation of COI peak (0.30L.min -1 .m 2 , [95%CI -0.34, 0.41]) and SVI peak (0.6ml.m 2 [95%CI -1.3, 2.5]), both of which declined with UC (COI peak : -0.68L.min -1 .m 2 , [95%CI -1.3, -0.32]; interaction, p= 0.008; SVI peak : -2.7ml.m 2 [95%CI -4.6, -0.9], interaction, p =0.014). There were no treatment effects of Activity on cardiac injury biomarkers or global longitudinal strain and no changes in left ventricular ejection fraction in either group. Conclusions: Intervening early in the allo-SCT process with an exercise and sedentary behavior intervention can have significant benefits for the preservation of patient’s cardiovascular reserve capacity. Our results may have important long-term implications for cardiovascular disease incidence and mortality in allo-SCT recipients. Clinical trial information: ANZCTR12619000741189.