Interval Exercise Training (IET) Is Feasible and May Improve Cardiorespiratory Performance Prior to Hematopoietic Cell Transplantation
Authors: Meeneghan Mathew , Snavely Anna , Smith-Ryan Abbie , Battaglini Claudio L , Reeve Bryce B , Basch Ethan , Bennett Antonia , Shatten Charlotte , Phillips Brett , Serody Jonathan , Gabriel Don A. , Jamieson Katarzyna Joanna , Coghill James , Armistead Paul M. , Shea Thomas C. , Wood William A. 
Published: November 2019

Abstract
INTRODUCTION: Peak oxygen consumption (VO2peak) and 6-minute walk distance (6MWD) measure overall fitness and functionality. Higher values have been shown to be directly related to lower mortality following allogeneic hematopoietic cell transplant (alloHCT) [Wood WA, et. al. Bone Marrow Transplant 2013;48:1342-1349. Kelsey CR, et. al. Cardiopulmonary exercise testing prior to myeloablative allo-SCT: a feasibility study. Bone Marrow Transplant (e-pub ahead of print 28 July 2014; doi:10.1038/bmt.2014.159.]. These parameters may represent targets for pre-HCT exercise interventions to ultimately improve post-HCT outcomes. Interval exercise training (IET), a type of exercise intervention that utilizes intermittent bouts of individualized high intensity exercise, has demonstrated the ability to induce rapid mitochondrial and enzymatic changes and to improve cardiorespiratory fitness in short periods of time. Thus, IET represents an attractive potential intervention for the time-limited pre-HCT setting. The purpose of this study was to evaluate the feasibility, safety and efficacy of 6 weeks of IET upon cardiorespiratory fitness (VO2peak) and 6MWD prior to HCT. We hypothesized that IET prior to HCT would be feasible and safe in the HCT population. Further, we hypothesized that IET prior to HCT would improve pre-HCT VO2peak and 6MWD. Because of the association of pre-HCT fitness with post-HCT mortality in the alloHCT patient population, this finding could support the use of IET in preparing this high-risk patient population to withstand the physiologic stress of transplantation.
METHODS: We planned to recruit 40 adult participants with planned auto (N=20) or allo (N=20) HCT for a study of a 6-week personalized, home-based IET intervention prior to HCT. IET consisted of a 2-week lead-in period followed by 4 weeks of thrice weekly sessions of five 3-minute intervals at 65-85% maximal heart rate (MHR). Each interval was followed by 2 minutes of rest. The mode of home-based exercise was decided in consultation with the participant and the exercise physiologist. A total of 18 sessions were prescribed for each participant. Intensity and compliance were assessed with heart rate monitors and accelerometers that were recorded weekly. Before and after the 6-week intervention 6MWD and exercise testing for the assessment of VO2peak conducted. Accelerometer data was used to assess total daily activity (steps per day) throughout the duration of the study.
RESULTS: Twenty-three participants (10 auto, 13 allo) are available for analysis at this time with recruitment ongoing (65% male; median age 53 years [range 27-75]; median BMI 27.6 kg/m2 [range 19.5-35.2]). For these participants, a median of 5 of the 6 prescribed weeks of exercise were completed, with a median of 10 interval exercise sessions performed during this time. Participants achieved target MHR for a median of 9 exercise sessions. Participants achieved a mean of 85% (SD±9) of MHR during exercise sessions. Subjects took an average of 5445 steps per day (SD±1738) throughout the intervention period. One patient reported dizziness, nausea, and shortness of breath during exercise, which resolved without complication; there were no other adverse events noted. For patients planning to undergo alloHCT, median VO2peak before the intervention was 18.8 ml/kg/min (IQR 17.1-26.4), and the median VO2peak improvement following the intervention was 3.7 ml/kg/min (IQR 2.6-5.0, p=0.002). For the entire population including planned autoHCT, these values were pre-intervention VO2peak 18.5 ml/kg/min (IQR 16.0-25.4) and VO2peak change 2.2 ml/kg/min (IQR 0.8-4.1, p=0.01). 6MWD also improved for those with planned alloHCT (median 37m, IQR 18-68, p=0.007) and for the overall group (median 40m, IQR 4-69, p=0.002).
CONCLUSIONS: Our findings demonstrate that patients planning to undergo auto or alloHCT are motivated and able to participate in a 6-week intensive, home-based interval exercise training intervention in the immediate pre-transplantation period. Participants were able to safely achieve high-intensity heart rates in the target range. Some participants could not complete the planned 6 weeks because of the timing of transplantation, while others completed the entire duration of the intervention. Preliminarily, the intervention appears to show efficacy in improving pre-HCT cardiorespiratory fitness as measured by VO2peak and 6MWD.

Disclosures
No relevant conflicts of interest to declare.