Randomized controlled trial on the effects of a supervised high intensity exercise program in patients with a hematologic malignancy treated with autologous stem cell transplantation: Results from the EXIST study

Abstract

BackgroundThis single blind, multicenter randomized controlled trial aimed to evaluate the effectiveness of a supervised high intensity exercise program on physical fitness and fatigue in patients with multiple myeloma or lymphoma recently treated with autologous stem cell transplantation.Methods109 patients were randomly assigned to the 18-week exercise intervention or the usual care control group. The primary outcomes included physical fitness (VO2peak and Wpeak determined using a cardiopulmonary exercise test; grip strength and the 30s chair stand test) and fatigue (Multidimensional Fatigue Inventory) and were assessed prior to randomization and after completion of the intervention or at similar time points for the control group. Multivariable multilevel linear regression analyses were performed to assess intervention effects.ResultsPatients in the intervention group attended 86% of the prescribed exercise sessions. Of the patients in the control group, 47% reported ≥10 physiotherapy sessions, which most likely included supervised exercise, suggesting a high rate of contamination. Median improvements in physical fitness ranged between 16 and 25% in the intervention group and between 12 and 19% in the control group. Fatigue decreased in both groups. There were no significant differences between the intervention and control group.ConclusionWe found no significant beneficial effects of the supervised high intensity exercise program on physical fitness and fatigue when compared to usual care. We hypothesized that the lack of significant intervention effects may relate to suboptimal timing of intervention delivery, contamination in the control group and/or suboptimal compliance to the prescribed exercise intervention.Trial registrationNetherlands Trial Register—NTR2341.

Lessons learnt from a process evaluation of an exercise intervention in patients treated with autologous stem cell transplantation

“…We previously hypothesised that the lack of significant effects may also be related to a suboptimal timing of the intervention delivery or to contamination in the control group (Persoon et al., 2017). Notwithstanding these hypotheses, given the lack of significant effects, it is not recommended to add the intervention in its current form to the usual care of patients recently treated with an auto‐SCT.…”

“…The study and intervention methods of EXIST have been described elsewhere (Persoon et al., 2010, 2017). Shortly, EXIST was a multicentre RCT that evaluated the effectiveness of a supervised moderate‐to‐high intensity exercise programme compared with a usual care control group on physical fitness and fatigue in patients recently treated with auto‐SCT.…”

“…The intervention programme consisted of an 18‐week supervised resistance exercise and interval training programme and five counselling sessions aiming to improve compliance with the exercise programme and to stimulate patients to pursue a physically active lifestyle (Persoon et al., 2010, 2017). Exercise sessions lasted 60 min and took place twice a week in week 1–12, and once a week in week 13–18.…”

“…In contrast to our hypothesis, in the EXercise Intervention after Stem cell Transplantation (EXIST) randomised controlled trial (RCT), we found no significant beneficial effects of an 18‐week supervised moderate‐to‐high intensity exercise programme on physical fitness and fatigue when compared to usual care (Persoon et al., 2017). Physical fitness and fatigue improved from baseline to first follow‐up in both the exercise and control group, but no significant between‐group differences in effects were found.…”

“…It is currently unclear whether this complex patient population—in terms of variability in side effects and co‐morbidities—was able to adhere to the exercise prescription. A suboptimal adherence to the prescribed exercise intervention may have contributed to the lack of significant between‐group differences in our study, in addition to suboptimal timing of intervention delivery and/or contamination in the control group (Persoon et al., 2017). …”