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 ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mstyle displaystyle="false"> <mml:mrow> <mml:mover accent="true"> <mml:mi mathvariant="normal">V</mml:mi> <mml:mo>˙</mml:mo> </mml:mover> </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 (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:mover accent="true"> <mml:mi mathvariant="normal">V</mml:mi> <mml:mo>˙</mml:mo> </mml:mover> </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: 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.