Preventing Allogeneic Stem Cell Transplant–Related Cardiovascular Dysfunction: ALLO-Active Trial
Authors: Hayley T. Dillon, Nicholas J. Saner, Tegan Ilsley, David S. Kliman, Stephen J. Foulkes, Christian J. Brakenridge, Andrew Spencer, Sharon Avery, Piet Claus, David W. Dunstan, Robin M. Daly, Steve F. Fraser, Neville Owen, Brigid M. Lynch, Bronwyn A. Kingwell, Andre La Gerche, Erin J. Howden
Journal: Circulation (2024)

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 (n=30) or usual care (UC; n=32). Activity comprised multicomponent exercise training (3 days/week) and sedentary time reduction (≥30 min/day) 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 ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mstyle displaystyle="false"> <mml:mrow> <mml:mrow> <mml:mover accent="true"> <mml:mi mathvariant="normal">V</mml:mi> <mml:mo>˙</mml:mo> </mml:mover> </mml:mrow> </mml:mrow> <mml:mrow> <mml:msub> <mml:mrow> <mml:mrow> <mml:mi mathvariant="normal">o</mml:mi> </mml:mrow> </mml:mrow> <mml:mrow> <mml:mrow> <mml:mn>2</mml:mn> <mml:mi mathvariant="normal">p</mml:mi> <mml:mi mathvariant="normal">e</mml:mi> <mml:mi mathvariant="normal">a</mml:mi> <mml:mi mathvariant="normal">k</mml:mi> </mml:mrow> </mml:mrow> </mml:msub> </mml:mrow> </mml:mstyle> </mml:math> ), exercise cardiac magnetic resonance imaging for peak cardiac volume (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 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mstyle displaystyle="false"> <mml:mrow> <mml:mrow> <mml:mover accent="true"> <mml:mi mathvariant="normal">V</mml:mi> <mml:mo>˙</mml:mo> </mml:mover> </mml:mrow> </mml:mrow> <mml:mrow> <mml:msub> <mml:mrow> <mml:mrow> <mml:mi mathvariant="normal">o</mml:mi> </mml:mrow> </mml:mrow> <mml:mrow> <mml:mrow> <mml:mn>2</mml:mn> <mml:mi mathvariant="normal">p</mml:mi> <mml:mi mathvariant="normal">e</mml:mi> <mml:mi mathvariant="normal">a</mml:mi> <mml:mi mathvariant="normal">k</mml:mi> </mml:mrow> </mml:mrow> </mml:msub> </mml:mrow> </mml:mstyle> </mml:math> 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: Multicomponent activity intervention during and after allo-SCT is beneficial for preserving patient 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