Preventing Allogeneic Stem Cell Transplant-Related Cardiovascular Dysfunction: ALLO-Active Trial

BACKGROUND:Allogeneic stem cell transplantation (allo-SCT) is an efficacious treatment for hematologic malignancies but can be complicated by cardiac dysfunction and exercise intolerance impacting quality of life and longevity. We conducted a randomized controlled trial testing whether a multicomponent activity intervention could attenuate reductions in cardiorespiratory fitness and exercise cardiac function (co-primary end points) in adults undergoing allo-SCT.METHODS:Sixty-two adults scheduled for allo-SCT were randomized to a 4-month activity program (activity; n=30) or usual care (UC; n=32). Activity comprised a multicomponent exercise training (3 days.week-1) and sedentary time reduction (>= 30 minutes.day-1) program and was delivered throughout hospitalization (approximate to 4 weeks) and for 12 weeks after discharge. Physiological assessments conducted before admission and at 12 weeks after discharge included cardiopulmonary exercise testing to quantify peak oxygen uptake (Vo2peak), exercise cardiac magnetic resonance imaging for peak cardiac (CIpeak) and stroke volume (SVIpeak) index, echocardiography-derived left ventricular ejection fraction and global longitudinal strain, and cardiac biomarkers (cTn-I [troponin-I] and BNP [B-type natriuretic peptide]).RESULTS:Fifty-two participants (84%) completed follow-up (25 activity and 27 UC); median (interquartile range [IQR]) adherence to the activity program was 74% (41%-96%). There was a marked decline in Vo2peak in the UC program (-3.4 mL center dot kg(-1)center dot min(-1) [95% CI, -4.9 to -1.8]) that was attenuated with activity (-0.9 mL center dot kg(-1)center dot min(-1) [95% CI, -2.5 to 0.8]; interaction P=0.029). Activity preserved exercise cardiac function, with preservation of CIpeak (0.30 L center dot min(-1)center dot m(-2) [95% CI, -0.34 to 0.41]) and SVIpeak (0.6 mL.m-2 [95% CI, -1.3 to 2.5]), both of which declined with UC (CIpeak, -0.68 L center dot min(-1)center dot m(-2) [95% CI, -1.3 to -0.32]; interaction P=0.008; SVIpeak, -2.7 mL.m-2 [95% CI, -4.6 to -0.9]; interaction P=0.014). There were no treatment effects of activity on cardiac biomarkers or echocardiographic indices.CONCLUSIONS:Intervening during and after allo-SCT with a multicomponent activity program during and after allo-SCT is beneficial for preserving a patient's cardiorespiratory fitness and exercise cardiac function. These results may have important implications for cardiovascular morbidity and mortality after allo-SCT.REGISTRATION:URL: https://anzctr.org.au/; Unique identifier: ACTRN12619000741189.