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

Abstract

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 (≈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 ([Formula: see text]), exercise cardiac magnetic resonance imaging for peak cardiac (CI_peak) and stroke volume (SVI_peak) 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 [Formula: see text] in the UC program (-3.4 mL‧kg^-1‧min^-1 [95% CI, -4.9 to -1.8]) that was attenuated with activity (-0.9 mL‧kg^-1‧min^-1 [95% CI, -2.5 to 0.8]; interaction P=0.029). Activity preserved exercise cardiac function, with preservation of CI_peak (0.30 L‧min^-1‧m^-2 [95% CI, -0.34 to 0.41]) and SVI_peak (0.6 mL.m^-2 [95% CI, -1.3 to 2.5]), both of which declined with UC (CI_peak, -0.68 L‧min^-1‧m^-2 [95% CI, -1.3 to -0.32]; interaction P=0.008; SVI_peak, -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.

Keywords: cardiac imaging techniques; cardio-oncology; cardiorespiratory fitness; cardiotoxicity; exercise; hematologic neoplasms; primary prevention.