This study demonstrated the overall effectiveness of an exercise program embedded in cancer care and evaluated the extent to which baseline function impacted the response to exercise following HSCT. The success of the program in improving all measures of physical function is important given the nature of the program provision. These improvements are not surprising as they are in line with much of the literature of controlled trials, confirming the benefits of exercise for 6MWD and cardiorespiratory fitness in HSCT recipients [8–11, 17]. Recent evidence suggests nearly half of HSCT recipients exhibit moderate to severe impairments in exercise capacity at one-year post-HSCT [28], thus demonstrating the important role for translation of exercise provision into care in this period. It is of note that meaningful relationships were observed between session attendance and improvements in 6MWD and maximal strength (leg press 1RM, seated row 1RM), suggesting session adherence was an important moderator of improvements in these outcomes. Balance also improved in response to the intervention, consistent with evidence from a systematic review among cancer survivors with balance impairments [37]. Furthermore, whilst the efficacy of interventions is commonly quantified using statistical measures, the use of minimal clinically important difference (MCID) values has been proposed as a key evaluator of translational research [38]. Despite differences in responsiveness to exercise according to baseline function, improvements in 6MWD and 30s-STS were both statistically and clinically significant for the two groups, with average improvements exceeding MCIDs for these measures [34–36]. Overall, the program was efficacious for the cohort in addressing the marked treatment related reductions in exercise capacity, strength and balance, which subsequently negatively affect QoL and interfere with daily function [5, 8].
Cancer-related fatigue has a complex aetiology involving inflammation, disease, treatment, demographic and psychological features [39]. Although the mechanisms by which exercise ameliorates fatigue are not well understood, the significant reduction in fatigue seen in the current study supports available literature among HSCT recipients. Whilst promising, post-intervention fatigue levels remained elevated, nearing moderate [25]. However, this is not unexpected as increased levels of fatigue commonly persist in the years following HSCT [3]. It is also noted that the recommended approach to post-treatment cancer-related fatigue is multimodal [42], and as such, the inclusion of evidence-informed complementary therapies may have contributed to the perceived improvement in fatigue.
The efficacy of the program on QoL varied between subscales, with no improvements evidenced in emotional wellbeing and non-significant improvements observed in physical wellbeing. Evidence for improvements in specific subsets of QoL among HSCT recipients is mixed [4, 13, 43], however the significant improvement in overall QoL is consistent with meta-analyses [9, 12]. With QoL negatively impacted by physiological and psychological consequences of HSCT, the significant improvement in overall QoL and across 3-subscales within the present study, albeit small, is promising.
One variable of interest in evaluating the feasibility of programs embedded in cancer care is the financial burden placed on patients. The relationship between financial support or investment and program attendance is vital in the implementation of exercise in cancer care, especially given the prolonged treatments and financial toxicity associated with haematological malignancies. Correlations between session attendance and magnitude improvement were observed for 4 measures. However few conclusions can be drawn due to the restrictions on session attendance placed upon the majority of participants included in this analysis who attended the program prior to the philanthropic donation. Programs of longer duration or without restrictions on number of permissible sessions should be studied to improve understandings of associations between session attendance and magnitude of improvement.
The impact of baseline function on exercise response was inconsistent. The inverse relationship between 6MWD at baseline and responsiveness to exercise is consistent with prior research in an HSCT setting [17]. However, whilst the ability to draw accurate comparisons with similar research is limited due to timing of exercise around HSCT and measurements use to assess outcomes, the absence of statistically significant differences between groups for remaining outcomes contrasts such research [17]. This disparity may be due to differences in extent of deconditioning at baseline. Participants in the current study were more deconditioned than expected based upon existing literature [8, 10, 11], which influenced the method used to stratify participants. Whilst low- and high-function was used to describe the groups, the overwhelming majority would be classified as low-function based on norms [29–31]. Hence, it is likely a ceiling effect was not present within this sample, thus contributing to the absence of significant differences between groups for most outcomes.
Although the absolute change in physical and functional measures was similar between groups for all outcomes except 6MWD, improvements in proportion to baseline values (percentage change) were consistently higher among the low-function group by virtue of their poorer scores at baseline. Larger effect sizes were also observed within this group for most outcomes. Therefore, despite failing to reach statistical significance for five of the six outcomes, differences in exercise response according to baseline function were present. Understanding such differences is vital in informing realistic goal setting and prescription. Future research should investigate the effect of varying exercise volume and intensity according to baseline function, with suggestions a greater exercise prescription may be necessary for those with higher baseline scores to elicit comparable benefits [17].
Furthermore, this was a multimodal exercise-based program that also included access to evidence-informed complementary medicine interventions and lifestyle education. Although not included in this analysis, future research would benefit from further examination of the impact of patient uptake of these complementary therapies due to understandings of the benefits of an integrative approach to cancer care [42].
Various limitations must be considered in interpreting these findings. Large amounts of data were unaccounted for, which reduced the sample size available for analysis. Although not unexpected given the nature of the retrospective data acquisition, future research would benefit from more defined data collection procedures. The pre-post design also presents a potential for the results to exaggerate a true effect, and without a controlled comparison, the extent to which improvements within the present study are attributable to the prescribed exercise remains open to investigation. As the ethics of conducting an RCT by means of depriving a control group of a recognised standard of care remain the subject of much debate, future research should instead focus on achieving an optimal program design by identifying characteristics of this population that interact with exercise training variables. Whilst evidence specific to HSCT is still in its infancy, greater levels of physical activity are associated with lower mortality risk across other cancer types [44]. As such, future translational research should investigate the potential impact of the program on improved self-efficacy and increased physical activity beyond supervised sessions as measured through validated assessment tools. Despite these limitations, the significant improvements were obtained from a ‘real world’ clinical setting. This suggests the improvements observed in specifically designed clinical trials can be translated into practice, thus signifying the efficacy of an existing program embedded in cancer care.