WHAT IS ALREADY KNOWN ON THIS TOPIC
Research trials have shown that exercise before, during and after stem cell transplantation is safe and can improve functional capacity and quality of life in people with haematological malignancies. Little is known about the implementation of exercise during stem cell transplantation into routine care and the acceptability in non-research participants.
WHAT THIS STUDY ADDS
Physiotherapist-led prehabilitation and rehabilitation as a key component of routine care during autologous stem cell transplant in myeloma at our UK centre is acceptable and shows benefit in improving functional outcomes and quality of life during preparation for and recovery from transplant.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
This embedded, pathway-based approach to implementing physiotherapist-led exercise in routine stem cell transplantation care can be adapted to the context of other centres wishing to optimise outcomes through enhanced rehabilitative support.
Introduction
Multiple myeloma is a plasma cell neoplasm that presents with a variety of clinical manifestations including bone destruction, hypercalcemia, anaemia and renal failure. While it remains incurable, new and effective therapies have resulted in many patients experiencing periods of disease control, punctuated by relapses and varying amounts of treatment-free intervals. Current standard-of-care for transplant-eligible, newly diagnosed myeloma, includes induction chemotherapy treatment, followed by peripheral blood stem cell harvest, high-dose melphalan and autologous stem cell transplantation (ASCT). 1 The recent incorporation of post-ASCT consolidation treatment, followed by maintenance therapy until disease progression has extended progression-free survival in myeloma.
While ASCT remains an important intervention in the management of myeloma in improving progression-free survival and overall survival it does not come without short-term and long-term adverse effects. A large population study (n=1969) found patients with myeloma reported the highest peak in fatigue and impaired well-being at 1-month post-ASCT, which subsequently improved over time but was still prevalent in 21%–26% of patients 1-year post-ASCT. 2 Qualitative studies exploring the experiences of patients with myeloma undergoing ASCT report it made them feel ‘dead’ 3 and they perceived their recovery as slow, negative and daunting. 4
Exercise-based rehabilitation plays an important role in reducing the negative side effects of cancer and its treatments. 5 Prehabilitation exercise interventions, aimed at optimising patients for cancer treatment, have been increasingly recognised for their positive effects in presurgical oncology populations. Benefits include improved clinical outcomes by the optimisation of physiological reserve resulting in enhanced resilience to treatment-related inactivity and deconditioning. 6 7 Meta-analyses of haematopoetic stem cell transplant populations found exercise interventions had a positive effect on functional capacity, lower limb strength, fatigue and quality of life (QoL). 8 9 In particular, the benefits were more pronounced if exercise interventions were commenced prior to transplantation. Therefore, exercise interventions commenced prior to ASCT could potentially translate into real-world healthcare savings by reducing hospital length-of-stay. 9 10 A pilot randomised controlled trial in patients with myeloma with exercise before and after ASCT found a high prevalence of functional deficits on initial referral, and reported a positive role for exercise in improving functional capacity, QoL and physical activity pre and post-ASCT. 11 Importantly, those who undertook exercise reported a positive and quicker recovery compared with control participants. 4
Translation of research findings into clinical practice remains a challenge for healthcare professionals, with implementation estimated to take approximately 17 years. 12 Such delays in innovative, evidence-based interventions may result in poorer clinical and functional outcomes, reduced QoL and higher healthcare-associated costs. At our centre, we sought to translate learning from a locally conducted pilot study undertaken within our myeloma ASCT pathway after promising results indicated improved functional capacity, QoL and experience of care. 4 11 Recognition of the benefits of this work from the research active clinical leadership team and divisional managers allowed for the development of an innovative new rehabilitation service focused on optimising patients for ASCT.
We aim to describe an overview of this prehabilitation and rehabilitation pathway designed to integrate seamlessly into, and complement, the established myeloma transplant service, and to present real-world findings related to function and QoL.
Materials and methods
Study design and setting
This service evaluation describes the implementation of a prehabilitation and rehabilitation pathway for transplant-eligible myeloma patients scheduled to undergo ASCT at a large tertiary referral cancer centre in London, United Kingdom. The pathway was implemented following a pilot study previously carried out at our centre 11 and was financed with fixed-term funding for specialist physiotherapist time (one whole time-equivalent Agenda for Change Band 8a). Elements of the pilot study intervention were adapted for translation to local care, as outlined in the patient and public involvement (PPI) section. In line with the UK Health Departments Research Ethics Service and Health Research Authority guidelines, approval from a Research Ethics Committee was not required as the study was a service evaluation 13 and local governance procedures for quality improvement were followed.
Participants
Patients with multiple myeloma who were referred for consideration for ASCT following induction treatment were identified in multidisciplinary team meetings and entered the pathway sequentially based on the date of their stem cell harvest consent consultation. There were no exclusion criteria. All patients referred for ASCT were included within this pathway and there was no reliance on clinician referral.
Overview of the prehabilitation and rehabilitation pathway
The pathway is illustrated in figure 1 and the intervention component is outlined in table 1 using the Template for Intervention Description and Replication 14 and Consensus on Exercise Reporting Template 15 checklists. Participants were notified via telephone prior to their assessment to introduce the programme and to set up a patient-facing hospital portal for the hospital electronic record system (EPIC MyChart). This was to facilitate completion of patient-reported outcomes measures (PROMs) prior to appointments. All physiotherapy assessments occurred face-to-face and coincided with existing myeloma clinical appointments. Pre-ASCT participants were enrolled on a one-off online education session and weekly remotely supervised group exercise sessions. Rehabilitation commenced once the patient was discharged from hospital. Patients were contacted at week 1 and week 3 following discharge to commence an unsupervised walking programme. At 4 weeks post-discharge, they would recommence a weekly remotely supervised group exercise session, which is continued up to 100 days post-ASCT.
Table 1
Prehabilitation and rehabilitation pathway summarised according to TIDieR and CERT checklists
ASCT, autologous stem cell transplant; Borg RPEBorg rating of perceived exhertion scaleCERT, Consensus on Exercise Reporting Template; HRR, heart rate reserve; TIDieR, Template for Intervention Description and Replication
| Prehabilitation and rehabilitation exercise programme during ASCT for myeloma | |
| Rationale | To support people with myeloma to prepare for and recover from ASCT |
| What: materials | Intervention materials:Intervention booklet (paper) including tasks to facilitate goal setting, identifying barriers/enablers, logsheets to record exercise and information on programme and Borg RPE scale. Booklet also included contributions from clinical psychologists regarding managing anxiety and worry related to treatment.Education session summaryExercise equipment:Resistance bands, multiple grades |
| What: procedures | Exercise programmeThe intervention included aerobic and resistance exercise and behaviour change support delivered over three phases:Prehabilitation phase: from baseline to admission for ASCT;Rehabilitation phase: from hospital discharge to 100 days post-ASCTPre-ASCT education sessionThe aim of the education session was to improve patients’ knowledge to help themselves prepare and manage their post-transplant recovery positively and included—what is an ASCT, how to prepare for ASCT, admission and discharge process, caregivers role in the ASCT process and techniques to psychologically prepare and cope with undergoing an ASCT. |
| Who: provider | Delivered by specialist physiotherapists with extensive experience working within myeloma.Education sessions were also led by the physiotherapist with input from a trainee clinical psychologist. |
| How: delivery | Group-based remotely supervised sessions and home-based individual exercise sessions |
| Prehabilitation: 1x online remotely supervised group exercise session and 2x unsupervised sessions per weekRehabilitation: 1x telephone contact in week 1 and week 3 following hospital discharge. From week 4 to D100: 1x online remotely supervised group exercise sessions and 2x unsupervised sessions per weekEducation session—1×1 hour session online | |
| Attendance of supervised sessions was recorded by the physiotherapy team. | |
| Incorporated behaviour change techniques as reported 37 | |
| Individually tailored and gradually progressed by the study physiotherapist weekly using Borg RPE scale.Circuit-based routine with aerobic and resistance exercises delivered in timed intervals with active rest. Sessions included active warm up and cool down.three sets of multi-joint functional exercises including upper body (shoulder press, wall press, seated row), lower body (squat, lunge, side lunge) and floor-based trunk stability (bridge, four-point kneeling arm and leg lifts, hundreds). | |
| Where: location | Group exercise sessions remotely supervised over video platform Zoom. |
| When, How much: dosage | Remotely supervised group sessionsFrequency 1 times per weekIntensity 11–16 Borg RPE scale. Duration 45 min sessions. Active intervals x45 seconds x3 rounds of each exercise set. Active rest 1 min between sets.Home exercise programmeFrequency 2 times per week independently. Aerobic activity working towards recommendation of 150 min of moderate intensity/week or 11–16 Borg RPE. |
| Tailoring: what, how | All exercise was individually tailored according to ability, presence of myeloma-related bone disease and individual symptoms and published principles. |
Assessments
Initial appointment and baseline assessment (T0) took place at consent for stem cell harvest. Follow-up assessment took place during preadmission ASCT consenting appointment (T1), typically 1 week prior to ASCT. Final follow-up assessment was approximately 100 days post-ASCT (T2). Patients completed PROMs, either electronically via electronic record system or on paper in clinic. PROMs included European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) QLQ-C30 16 and EuroQol EQ5D-5L 17 measures of QOL and Duke Activity Status Index. 18 Participants underwent a 6 min walk test (6MWT), carried out according to guidelines 19 using a 30 m track, and a 1 min timed sit-stand test (1minSTS). A reference equation was used to determine a predicted 6MWT distance for each participant based on their age and sex. 20 Each participant’s actual 6MWT distance and their predicted distance were used to calculate percentage of predicted score. Validated reference scores were used to determine if patients’ 1minSTS outcomes were in line with those expected for their age and sex. 21
Number of weeks between T0 assessment and day of ASCT (prehabilitation phase) and between hospital discharge and T2 assessment (rehabilitation phase) was calculated to ascertain time available to receive input during both phases of the pathway. Length of stay was retrieved from electronic hospital records and compared with historical data, matched for age, gender, conditioning dose and admission type (inpatient vs ambulatory care). Attendance of remotely supervised sessions was recorded and summarised, as were reasons given for non-attendance. On completion of rehabilitation, participants were asked to complete an online anonymous patient experience questionnaire (reported separately).
Analysis
Demographics, disease characteristics and baseline outcomes were presented using descriptive statistics (mean with SD, median and IQR and range, or frequencies and proportions). Paired sample t-tests were used for pre–post assessment of outcomes. Parametric student t-tests were used where assumptions of distribution and normality were met, otherwise non-parametric Wilcoxon rank test was used. Data were summarised using Microsoft Excel and Jamovi. 22 Standards for Quality Improvement Reporting Excellence (SQUIRE) guidelines were also followed. 23
Patient and public involvement
The authors conducted a PPI workshop prior to the implementation of this project. The aim of this workshop was to seek patient input into the transition of the original research-delivered intervention into a clinical service. This input led to the integration of a patient education session and enhancement of the rehabilitation phase to include remotely supervised group exercise sessions, instead of telephone-based support.
Results
Participant characteristics
Between May and October 2023 (6 months), 48 participants were assessed by physiotherapists at the preharvest baseline timepoint (T0). Of these, 46 (96%) proceeded to admission for ASCT. Two patients did not proceed (due to disease progression (n=1) and not deemed fit to proceed (n=1)), and their data were removed from the analysis.
The cohort had a mean age of 60.8 (SD 7.8) years, was 57% male with majority of patients being of white ethnicity (74%), married or in civil partnership (65%) and retired (43%). Most patients (98%) were undergoing their first ASCT, and had undergone one line of treatment (96%), with a median time from diagnosis to baseline assessment of 5 months (IQR 4–6). The majority (57%) received standard-of-care induction chemotherapy with daratumumab, velcade, thalidomide and dexamethasone, receiving an average of 4.2 (SD 0.7) cycles. 89% of patients had myeloma-related bone disease on imaging and 41% required immobilisation in a spinal orthotic/brace. Patient characteristics and disease features are presented in tables2 3 .
Table 2
Patient characteristics
| All patients (n=46) | |
| Age median (IQR) | 61.5 (57, 66.8) |
| Age mean (SD) | 60.8 (7.8) |
| Age range | 42–73 |
| Sex male n (%) | 26 (57%) |
| Body mass index (BMI) mean (SD) | 27.3 (4.5) |
| Overweight (25–29.9 kg/m 2 ) | 23 (50%) |
| Obese (>30 kg/m 2 ) | 11 (24%) |
| Healthy weight (18.6–24.9 kg/m 2 ) | 11 (24%) |
| Underweight (<18.5 kg/m 2 ) | 1 (2%) |
| Ethnicity n (%) | |
| White British/Other White background | 34 (74%) |
| Black British/Other Black background | 6 (13%) |
| Asian Indian/Other Asian background | 3 (7%) |
| Other background | 1 (2%) |
| Not recorded in records | 2 (4%) |
| Martial status n (%) | |
| Married/civil partnership | 30 (65%) |
| Single | 12 (26%) |
| Separated | 2 (4%) |
| Widowed/surviving civil partnership | 2 (4%) |
| Employment status n (%) | |
| Retired | 20 (43%) |
| Full-time employment | 8 (17%) |
| Self-employed | 5 (11%) |
| Unemployed | 5 (11%) |
| Part-time employed | 3 (7%) |
| Part-time self-employed | 1 (2%) |
| Working from home | 1 (2%) |
| Other | 2 (4%) |
| Missing | 1 (2%) |
| Outdoor mobility status n (%) | |
| Independent | 35 (76%) |
| Uses walking aid | 7 (15%) |
| Wheelchair required | 3 (6%) |
| Assistance+walking aid required | 1 (2%) |
Table 3
Disease characteristics
ASCTautologous stem cell transplantationCTLSOcervical-thoracolumbosacral orthosisDVCddaratumumab, bortezomib, cyclophosphamide and dexamethasoneDVRddaratumumab, bortezomib, lenalidomide and dexamethasoneDVTddaratumumab, bortezomib, thalidomide and dexamethasoneISSInternational Staging SystemTLSOthoracolumbosacral orthosisVCRDbortezomib, cyclophosphamide, lenalidomide and dexamethasoneVTD-PACEbortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide and etoposide
| All patients (n=46) | |
| Disease type n (%) | |
| IgG kappa | 19 (41%) |
| IgG lambda | 10 (22%) |
| Kappa light chain | 5 (11%) |
| IgA kappa | 4 (9%) |
| IgA lambda | 4 (9%) |
| Lambda light chain | 3 (7%) |
| IgA | 1 (2%) |
| ISS at diagnosis n (%) | |
| 1 | 12 (26%) |
| 2 | 12 (26%) |
| 3 | 9 (20%) |
| Not known | 13 (28%) |
| Number of lines of treatment n (%) | |
| 1 | 44 (96%) |
| 2 | 1 (2%) |
| 3 | 1 (2%) |
| Bone disease n (%) | |
| Axial disease | 20 (44%) |
| Axial and peripheral disease | 19 (42%) |
| Peripheral disease | 1 (2%) |
| No bone disease | 5 (11%) |
| Required spinal brace n (%) | |
| TLSO | 11 (24%) |
| CTLSO | 8 (17%) |
| No brace | 27 (59%) |
| Previous radiotherapy n (%) | 11 (24%) |
| Previous surgery for myeloma disease n (%) | 4 (9%) |
| Induction regime n (%) | |
| DVTd | 26 (57%) |
| VCRD (trial) | 10 (22%) |
| DVd+DVTd | 2 (4%) |
| VTD | 1 (2%) |
| DVCd+DCd | 1 (2%) |
| DVd | 1 (2%) |
| VCRD+VCRD+ Isa (trial) | 1 (2%) |
| DVRd+DVTd | 1 (2%) |
| DVCd | 1 (2%) |
| VTD-PACE | 1 (2%) |
| DVCd+DVTd | 1 (2%) |
| Number of cycles of induction chemotherapy | |
| Age mean (SD) | 4.2 (0.7) |
| Age range | 2–7 |
| First ASCT n (%) | 45 (98%) |
| Time from diagnosis to baseline assessment (months) | |
| Median (IQR) | 5 (4, 6) |
| Range | 2–173 |
Baseline function and QOL
At baseline assessment, during preharvest clinical review, the mean distance walked by participants in the 6MWT was 451.4 m (SD 106.5, range 180–750 m, n=43). The median percentage of predicted score for the cohort was 70.7% (IQR 61–80.2) and 72% of the cohort walked a distance less than 80% of their predicted distance.
The mean repetition for the 1 min STS test was 21.9 (SD 11.2, range 0–56, n=46). 72% of the cohort produced below average (<25th centile) scores for their age and sex, with 48% of patients producing a below 2.5th centile score, indicating severely impaired lower limb strength endurance.
The EQ5D-5L was dichotomised into ‘no problems’ versus ‘some level of problem’, with the majority of patients reporting some level of problem in 4 out of 5 domains at baseline. Problems with carrying out ‘usual activities’ were most commonly reported (84% n=37), with most reporting slight or moderate problems (68% n=30), followed by experiencing ‘pain’ (78% n=34) and problems with ‘mobility’ (59% n=26). Nearly half of patients (46% n=20) reported moderate or severe levels of pain. Over half the cohort (52% n=23) reported some level of ‘anxiety/depression’. ‘Self-care’ had the lowest reported problems with 33% (n=14) of patients reporting problems, mostly slight. The EQ5D visual analogue scale (VAS) measure of ‘your health today’ had a median score of 70/100 [IQR 44.0, 80.00, n=41]. Baseline scores for selected domains of the EORTC-C30 are outlined in table 4 .
Table 4
Changes in functional outcomes and PROMs
* Non-parametric Wilcoxon rank test used. EORTC QLQ-C30European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire EQ5D-5LEuroQol EQ5D-5LMETsmetabolic equivalentsPROMspatient-reported outcomes measures
| Baseline(T0) | Pre-admission(T1) | D100(T2) | Change in prehab phase (T1−T0) | Change baseline to D100 (T2−T0) | |
| 6 min walk test (6MWT) (m) | n=31 | n=26 | n=31 | n=26 | |
| Mean (SD) | 445.7 (111.5) | 505.9 (121.8) | 504.3 (105.7) | +60.2 m(95% CI 41.5 to 78.9) p<0.001 | +62.8 m(95% CI 40.7 to 84.9) p<0.001 |
| % of predicted 6MWT | |||||
| Mean (SD) | 68.3 (16.6) | 77.5 (18.5) | 78.2 (17.2) | +9.3 %(95% CI 6.5 to 12.1) p<0.001 | +9.8 %(95% CI 6.4 to 13.6) p<0.001 |
| Timed 1 min sit to stand test (repetitions) | n=35 | n=26 | n=35 | n=26 | |
| Mean (SD) | 21.3 (11.6) | 28.1 (12.3) | 30.9 (12.9) | +6.8 reps(95% CI 4.9 to 8.7) p<0.001 | +9.1 reps(95% CI 5.4 to 12.8) p<0.001 |
| Duke Activity Status Index | n=28 | n=26 | n=28 | n=26 | |
| Calculated METs (median) * | 5.7 | 7.0 | 5.6 | +1.3p<0.001 | −0.1p=0.1 |
| EORTC QLQ-C30 | n=37 | n=31 | n=37 | n=31 | |
| Global health status (QL) | 54.7 (19.1) | 60.6 (18.3) | 66.7 (17.2) | +5.9(95% CI 1.2 to 10.5), p=0.02 | +11.8(95% CI 5.7 to 17.9), p<0.001 |
| Summary score | 72.9 (14.2) | 75.7 (15.1) | 78.9 (14.1) | +2.8(95% CI −1.4 to 7.1), p=0.19 | +5.7(95% CI 1.7 to 9.8), p=0.008 |
| Physical functioning (PF) | 64.7 (23.1) | 72.6 (24.0) | 76.6 (17.9) | +7.9(95% CI 2.9 to 13.0), p=0.003 | +13.8(95% CI 7.7 to 19.8), p<0.001 |
| Role functioning (RF) | 45.1 (31.2) | 63.1 (30.0) | 65.1 (28.3) | +18.0(95% CI 8.7 to 27.3), p<0.001 | +19.9(95% CI 5.1 to 9.5), p<0.001 |
| Emotional functioning (EF) | 77.7 (21.2) | 77.7 (20.3) | 78.0 (21.3) | 0.0(95% CI −4.9 to 4.9), p=1.0 | +3.0(95% CI −1.6 to 7.5), p=0.2 |
| Social functioning (SF) | 52.7 (31.6) | 55.4 (29.9) | 58.6 (31.3) | +2.7(95% CI −7.0 to 12.4), p=0.57 | +7.0(95% CI −2.5 to 16.4), p=0.14 |
| Symptom: fatigue (FA) | 40.2 (25.4) | 33.0 (19.7) | 31.5 (22.6) | −7.2(95% CI −14.7 to 0.3), p=0.06 | −7.2(95% CI −14.8 to 0.5), p=0.07 |
| Symptom: pain (PA) | 38.3 (30.4) | 33.8 (29.5) | 29.6 (25.0) | −4.5(95% CI −13.0 to 4.0), p=0.29 | −9.7(95% CI −20.7 to 1.4), p=0.08 |
| n=31 | n=29 | n=31 | n=29 | ||
| EQ5D-5LVisual analogue scaleMean (SD) | 61.0 (21.7) | 69.7 (18.5) | 74.2 (14.9) | +8.7(95% CI 2.87 to 14.8), p=0.006 | +9.5(95% CI 2.8 to 16.2), p=0.007 |
Outcomes following prehabilitation
Of the 46 patients who were assessed at baseline and proceeded to ASCT, 39 (85%) underwent a post-prehabilitation assessment prior to admission for ASCT (T1). Reasons for not undergoing a T1 assessment included missing their preadmission clinical appointment, in which a subsequent physiotherapy assessment not undertaken (n=5, 71.4%), patient did not attend clinical assessment (n=1, 14.3%) or declined to undergo assessment (n=1, 14.3%). There were no differences between the 39 patients included in the pre–post analyses of outcomes compared with the overall cohort in terms of clinical and disease characteristics. They had a mean age of 60.4 (SD 7.9) years, were 56% male and mostly of white ethnicity (72%). The distribution of martial and employment status was the same, as was median time from diagnosis to baseline assessment.
Descriptive summaries of each outcome for participants included in the pre–post analyses are summarised in table 4 . There was a statistically significant improvement in 6MWT distance (+60 m, 95% CI 41.5 to 78.9, p<0.001) and 1min-STS (+6.8 repetitions 95% CI 4.9 to 8.7, p<0.001) after prehabilitation. Domains of the EORTC which improved significantly included global QoL (+5.9, 95% CI 1.2 to 10.5, p=0.02), physical functioning (+7.9, 95% CI 2.9 to 13.0, p=0.003) and role functioning (+18.0, 95% CI 8.7 to 27.3, p<0.001). The EQ5D VAS score improved significantly (+8.7, 95% CI 2.87 to 14.8, p=0.006).
Outcomes following rehabilitation
To evaluate the combined effect of prehabilitation before and rehabilitation after ASCT, a pre–post analysis was undertaken comparing baseline outcomes (T0) with day 100 (D100) post-ASCT outcomes (T2). Of the 39 patients included in the pre–post prehabilitation analysis, 33 (85%) also completed outcomes at D100 post-ASCT (T2). Reasons for not undergoing D100 assessment included attending appointment but not completing assessments (n=2, 33%), not reaching the D100 timepoint within the timeframe of the project (n=2, 33%), did not attend clinical assessment (n=1, 17%) or D100 clinical appointment was missed and a physiotherapist assessment was not arranged (n=1, 17%).
Between baseline and 100 days post-ASCT, there were improvements in 6MWT distance (+62.8 m, 95% CI 40.7 to 84.9, p<0.001) and 1min-STS (+9.1 reps, 95% CI 5.4 to 12.8, p<0.001). EORTC domains of global QoL (+11.8, 95% CI 5.7, 17.9, p<0.001) and physical functioning (+13.8, 95% CI 7.7, 19.8, p<0.001) improved significantly. There were improvements in role functioning (+19.9, 95% CI 5.1 to 9.5, p<0.001) and overall summary score (+5.7, 95% CI 1.7 to 9.8, p=0.008). The EQ5D VAS score improved (+9.5, 95% CI 2.8 to 16.2, p=0.007).
Attendance of prehabilitation and rehabilitation sessions
Potential time available for prehabilitation input was estimated from the mean number of weeks between baseline assessment (T0) and day of ASCT, which was 6.8 weeks (SD 3.3, 95% CI 5.9 to 7.8, n=46). Of the 46 patients assessed preharvest, 31 (67%) participants attended at least one remotely supervised group prehabilitation exercise session. Of these participants, the median number of sessions attended within the prehabilitation phase was four sessions (IQR 3–5). 3 (6%) declined to take part in group sessions, 6 (13%) were booked to attend sessions but did not attend any, 6 (13%) exercised independently. The most common reason for not attending or cancelling a booked prehabilitation session was having another medical appointment.
With regards to time available to potentially benefit from rehabilitation input, the mean number of weeks between hospital discharge following ASCT and day of D100 clinical assessment was 11.8 weeks (SD 1.7 95% CI 11.3 to 12.4, n=44). 39 (85%) out of 46 patients received early rehabilitation telephone support postdischarge in line with the protocol (median 2 calls (IQR 1.8–2)). Of the 31 patients who attended the prehabilitation classes, 27 (87%) attended at least one remotely supervised group exercise session, with median number of sessions was 6 (IQR 4–6.5) attended in the rehabilitation phase. Four patients (13%) who were expected to attend the rehabilitation exercise classes were unable to attend any due to hospital readmissions and as a result required more telephone calls (median 5.5 calls (IQR 4.3–6.3)). 3 patients (8%) did not answer the calls. The most common reasons for not attending or cancelling a booked rehabilitation session were related to logistical challenges with sessions falling on public holidays or lack of cover for physiotherapist annual leave.
Length of stay
The median length of stay in those who proceeded to ASCT was 17 days (IQR 15–23, n=43). There was no difference in total length of stay between the service evaluation participants and matched historical data.
Discussion
This service development project focused on translating local research data into the delivery of a prehabilitation and rehabilitation pathway integrated into standard-of-care practice for patients with myeloma undergoing ASCT at our centre. Delivered in a hybrid format, participants were assessed face-to-face during routine clinic appointments and engaged in remotely supervised exercise intervention. This structure allowed for the objective assessment of functional outcomes in clinic and increased the ability to engage in supervised exercise sessions remotely. This approach has been highlighted as preferable to patients with myeloma due to the wide geographical reach of specialist haematopoietic transplant centres in the UK and reported reluctance to engage in frequent travel to attend face-to-face sessions. 4 24 25
This study found deficits in functional capacity and QoL, which may be higher than anticipated. Patients with transplant-eligible myeloma are considered to be physically ‘fitter’ than their non-transplant eligible counterparts, in order to tolerate high-dose treatment with melphalan. 26 At baseline, patients assessed in this evaluation had lower than expected QoL scores. EORTC domains of physical functioning, role functioning, social functioning and global health were all low compared with published reference values for patients with myeloma. 27 EORTC group scores for physical functioning were lower than published cut-off scores for clinical importance among patients with cancer. 28 In contrast, the cohort had lower median scores for fatigue and pain than myeloma population reference values, 27 indicating lower symptomology. However, when considering thresholds for clinical importance in mixed cancer populations, the cohort score for pain did indicate clinically important levels of pain, 28 which may reflect the high representation of patients with myeloma-related bone disease and history of spinal bracing.
There was a high proportion of patients with walking distance and sit-to-stand test results that were lower than published reference values. Literature indicates that a 6MWT score of <80% predicted is indicative of impaired functional capacity, 29 and 1min-STS scores of <2.5th centile reference scores is indicative of severely impaired lower body muscular strength and endurance. 21 72% of participants produced 6MWT distances<80% predicted and 48% were in the lowest 2.5th centile for 1min-STS, indicating high levels of impaired functional capacity and fitness among these patients prior to stem cell harvest. These proportions are greater than reported in our previous pilot study, where 53% (n=19) of participants were found to have impaired functional capacity. 11 The measurement of such outcomes in a real-world population reinforces published data that the prevalence of functional deficits is greater than those from reference study populations. Furthermore, it builds on the existing literature, which emphasised the need for objective measures of function to be included as part of routine pre-transplant clinical assessments. 30
Clinically significant improvements in patient function and QoL prior to admission for ASCT were observed in this service evaluation and maintained by D100 post-ASCT. Walking distance and lower limb strength improvements from prehabilitation were two times that of the published minimal importance differences for these measures respectively 31 33 and further gains in lower limb strength were evident with rehabilitation input following ASCT. Mean 6MWT distance for this cohort at preadmission and D100 post-ASCT were in line with those found in patients with myeloma more than 1-year post-ASCT, 34 which could suggest earlier return of functional capacity with timely rehabilitation intervention around ASCT. Greater than MID changes in EORTC QoL domain of physical functioning corroborates the objectively measured changes in walking distance and strength. EORTC domains of global QoL and physical functioning improved within or beyond the MID suggested for patients with myeloma, respectively. 35 The significant improvement in EQ5D VAS score after prehabilitation was also in line with MID for patients with cancer. 17 These combined effects, along with positive improvements in other domains and overall QoL, highlight the importance of patient engagement in physical interventions on QoL and support the need for rehabilitative approaches in cancer treatment pathways. 5
The value of utilising the time prior to ASCT admission cannot be underestimated. The effects of diagnosis and early induction treatment on QoL and physical activity have been documented in myeloma. 2 Furthermore, the desire from patients to engage in exercise to ‘build up’ prior to ASCT 3 4 is contrasted with experiences of lack of specialised support needed to overcome the barriers to exercising independently in the context of bone disease and pain. 4 25 This service evaluation indicates promise in embedding pathway-based prehabilitation, with hybrid delivery using remotely supervised exercise and education, as an effective tool for optimising patients in the time frame pre-ASCT.
The acceptability of prehabilitation and rehabilitation around ASCT is further evidenced by this service evaluation. Real-world delivery of clinical rehabilitation interventions may give a more realistic insight into uptake and adherence to interventions previously tested in research settings. 36 By offering this service sequentially to patients referred for ASCT, and by conducting physiotherapy assessments aligned with myeloma clinical appointments, we were able to collect objective measures and comprehensive real-world follow-up data. This supports the feasibility of integrating functional and PROM assessments along standard-of-care without significant service disruption. Attendance to at least one remotely delivered exercise session was high in both prehabilitation and rehabilitation phases, with average attendance of four and six sessions in the 7 and 12 weeks available in each phase, respectively. Patients requiring additional telephone support due to slower recovery and/or hospital readmissions post-transplant influenced the lower attendance rate in the rehabilitation phase. The use of stratification of rehabilitation input depending on baseline outcomes or response to hospital admission was not undertaken but is planned for future evaluations. Lower physical functioning was noted to be a significant factor in influencing attendance, with those who had poorer physical function at baseline, and less social support, being impacted the most. Stratification of patients according to functional deficits and self-efficacy to engage in independent exercise programmes could help facilitate tailoring of rehabilitation support, including strategies to help overcome barriers to access, and allow for greater efficiency in resource allocation and intervention strategies. In the context of limited workforce resources and increasing healthcare demand, such an approach could help identify patients who may require additional input, and therefore facilitate equitable access to healthcare interventions.
This work has a number of limitations. As a service development evaluation in a single UK centre, these results may lack applicability to other transplant centres with patients with myeloma undergoing ASCT. Lack of control group or historical data related to function and QoL limits the interpretation of results. In addition, adherence to exercise programmes, particularly in terms of duration and intensity, and whether carried out with and without supervision, was not captured. Although our previous research showed promise in increasing physical activity, the local EHR lacked a reliable measurement for physical activity as part of standard of care, which would have been useful in assessing activity outside of specific physiotherapy interventions.
Conclusions
The time between induction chemotherapy and admission for ASCT provides an opportunity to support patients with myeloma to regain physical function and QoL lost during induction treatment and to optimise their performance status prior to proceeding to transplant. This service evaluation of a physiotherapist-led exercise prehabilitation and rehabilitation pathway, built on previous locally delivered research, reinforces the potential benefits of integrating a pathway-based prehabilitation intervention alongside standard medical and nursing care in patients with myeloma planned for ASCT. Hybrid delivery of exercise interventions using face-to-face assessments and remotely supervised group exercise and education is a feasible and promising approach to optimising patients pre-ASCT. This study supports the use of objective measures of function and QoL as important tools for the comprehensive assessment of fitness prior to undergoing ASCT.
The higher-than-expected levels of impaired functional capacity evident in our patients prior to ASCT highlight the impact of haematological malignancies and disease-related morbidity on overall fitness, even for those deemed suitable to proceed to transplant with high-dose melphalan. Despite this, the introduction of physiotherapy interventions resulted in clinically significant improvements in functional outcomes that were seen prior to admission for ASCT and were maintained at 100 days post-ASCT. The role of prehabilitation and rehabilitation in enhancing outcomes for patients with myeloma is promising and warrants further investigation using both research and real-world studies.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Patient consent for publication: Not applicable.
Ethics approval: In line with the UK Health Departments Research Ethics Service and Health Research Authority (HRA) guidelines, approval from a Research Ethics Committee (REC) was not required as the study was a service evaluation and local governance procedures for quality improvement were followed. Participants gave informed consent to participate in the study before taking part.
Provenance and peer review: Not commissioned; externally peer-reviewed.
Patient and public involvement: Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
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Data availability statement
Data are available upon reasonable request.