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

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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 [VO2peak]) 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 VO2peak, (2) exercise cardiac magnetic resonance imaging to determine peak cardiac output and stroke volume index (COIpeak and SVIpeak), (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 VO2peak (-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 COIpeak (0.30L.min-1.m2, [95%CI -0.34, 0.41]) and SVIpeak (0.6ml.m2 [95%CI -1.3, 2.5]), both of which declined with UC (COIpeak: -0.68L.min-1.m2, [95%CI -1.3, -0.32]; interaction, p= 0.008; SVIpeak: -2.7ml.m2 [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.