
==== Front
BMJ Open
BMJ Open
bmjopen
bmjopen
BMJ Open
2044-6055
BMJ Publishing Group BMA House, Tavistock Square, London, WC1H 9JR

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10.1136/bmjopen-2024-084372
bmjopen-2024-084372
Protocol
Oncology
1717
1506
Investigating the impact of multidisciplinary prehabilitation on deconditioning in patients eligible for haematopoietic allogenic stem cell transplantation: protocol for a feasibility trial
Naumann Karlee 1karlee.naumann@sa.gov.au

https://twitter.com/bensinghphd
http://orcid.org/0000-0002-7227-2406
Singh Ben 2ben.singh@unisa.edu.au

Bushaway Samuel 1samuel.bushaway@sa.gov.au

Crane Rhiannon 1rhiannon.crane@sa.gov.au

Deepak Swapna 1swapna.deepak@sa.gov.au

Hartland Amie 1amie.hartland@sa.gov.au

Konstantopoulos Peter 1peter.konstantopoulos@sa.gov.au

Mansell Ella 1ella.mansell@sa.gov.au

Marinelli Vanessa 1vanessa.marinelli@sa.gov.au

Pallotta Vanessa 1vanessa.pallotta@sa.gov.au

Tolfts Annabel 1annabel.tolfts@sa.gov.au

Virieux Alison 1alison.virieux@sa.gov.au

Wall Michelle 1michelle.wall@sa.gov.au

Wilksch Sarah 1sarah.wilksch@sa.gov.au

Zhuang Mabel 1mabel.zhuang@sa.gov.au

Atkinson Morgan 1morgan.atkinson@sa.gov.au

Maher Carol 2carol.maher@unisa.edu.au

1 Royal Adelaide Hospital, Adelaide, South Australia, Australia
2 University of South Australia, Adelaide, South Australia, Australia
Dr; ben.singh@unisa.edu.au
None declared.

2024
05 9 2024
14 9 e08437217 1 2024
21 8 2024
Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

ABSTRACT

Background

Assessing multidisciplinary prehabilitation strategies becomes crucial to pre-emptively counter the physical, psychological and social negative impacts experienced during an allogenic haematopoietic stem cell transplant (allo-HSCT) among acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients. Current evidence is restricted to studies during induction chemotherapy, omitting rehabilitation interventions and predominantly using exercise-only approaches without a multidisciplinary framework. The aim of this study is to investigate the feasibility, safety and preliminary efficacy of multidisciplinary prehabilitation in adults offered allo-HSCT.

Methods and analysis

This 8-week single-group pre-post feasibility study aims to pilot a multidisciplinary prehabilitation intervention for participants undergoing allo-HSCT, with a focus on feasibility and safety. Participants, aged 18 or older, diagnosed with AML or MDS, and offered allo-HSCT, will be recruited between June 2023 and July 2024. The multidisciplinary prehabilitation intervention, conducted by the cancer allied health team at the Royal Adelaide Hospital, includes exercise physiology, physiotherapy, dietetics, social work, occupational therapy and psychology interventions. Consistent with a multidisciplinary treatment approach, each component is tailored to address different aspects of patient care, and adherence calculations will assess patient engagement and compliance. In addition, participants will continue to receive usual care from cancer allied health staff. The primary outcome of the study is to assess the feasibility of a multidisciplinary prehabilitation intervention by evaluating intervention uptake, retention, adherence, acceptability and safety. Secondary outcomes are leg strength, upper-body strength, aerobic fitness, falls risk, anthropometry, nutritional status, quality of life, anxiety, depression, self-efficacy for coping with cancer and distress.

Ethics and dissemination

Ethics approval for this study has been provided by the Central Adelaide Local Health Network (HREC 2022/HRE00284). Recruitment for the study commenced in June 2023 and will continue until July 2024. The methods have been designed and are reported according to the SPIRIT and CONSORT-pilot study checklist.

Trial registration number

The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000052639.

Bone marrow transplantation
HAEMATOLOGY
PREVENTIVE MEDICINE
Medical Research Future Fund Emerging Leader Grant GNT1193862
==== Body
pmcSTRENGTHS AND LIMITATIONS OF THIS STUDY

A key strength is the comprehensive, multidisciplinary approach addressing physical and psychosocial care for allogeneic haematopoietic stem cell transplantation patients.

The primary focus of this study on assessing the feasibility of implementing the prehabilitation intervention in a real-world clinical setting, recognising the practical challenges that may arise during implementation.

The study’s targeted inclusion criteria, specifically focusing on acute myeloid leukaemia or myelodysplastic syndrome patients offered haematopoietic allogenic stem cell transplant, adds precision to participant selection and enhances the study’s relevance to this specific patient population.

The single-group design lacks a control group, limiting attribution of outcomes to the prehabilitation intervention.

The 8-week intervention period with short-term follow-up may not capture long-term impacts on overall health and well-being.

Background

Acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) are haematological malignancies affecting the bone marrow. Five-year survival rates range between 15% and 25% for AML,1 while median survival for patients with lower-risk and higher-risk MDS is 3 to 10 years, and less than 3 years, respectively.2 Survival rates for AML and MDS vary depending on several factors, including the stage of the disease at diagnosis, the patient’s age and the specific treatments used. Haematopoietic allogenic stem cell transplant (allo-HSCT) is a potentially curative treatment for a variety of haematological malignancies, bone marrow failure syndromes and some autoimmune diseases.3 However, allo-HSCT is associated with significant morbidity and mortality, hospital-acquired complications and prolonged hospitalisation.4 Deconditioning is also a common complication of allo-HSCT, characterised by a decline in physical function, muscle strength and endurance.5 Moreover, the profound effects of allo-HSCT extend beyond physical decline, significantly influencing patients’ psychological well-being, social interactions and occupational functioning.6 Overall, allo-HSCT is associated with prolonged hospital stays, increased healthcare costs and decreased quality of life.7 8 Allo-HSCT can provide potentially longer life expectancy and, for some, a curative option, but the consequences of treatment, including the known late effects of allo-HSCT, can be detrimental to patients’ quality of life. Therefore, new efforts are needed to curtail the length of stay and improve patient outcomes.

Prehabilitation is a comprehensive approach designed to optimise patients’ physical function, psychological and psychosocial well-being before surgery or other medical interventions such as cancer treatment.9 Multidisciplinary prehabilitation combines exercise, nutritional, psychological and psychosocial support to enhance general health and well-being prior to the medical intervention, to help the patient withstand postoperative inactivity and associated decline.9 Multidisciplinary prehabilitation has shown to be effective in improving quality of life, functional status, physical capacity and mental health.1015 In addition, prehabilitation can speed up recovery, reduce the risk of infection or other complications, and improve the effectiveness of cancer treatment and reduce the length of hospital stay in various cancers, including breast, prostate, colorectal and abdominal cancers.1015 However, the specific benefits of this approach in allo-HSCT patients are under-researched.

A limited number of studies have investigated the effect of exercise interventions in AML and MDS patients and prior to allo-HSCT. A randomised controlled trial (RCT) for patients with AML (n=83) undergoing induction chemotherapy showed that supervised moderate-intensity exercise performed 4–5 days per week throughout induction chemotherapy had a recruitment rate of 56%, 96% retention and 54% adherence. Significant improvements in quality of life, fatigue, aerobic fitness, lower body strength and grip strength were observed in the exercise group.16 A 12-week non-randomised feasibility trial involving MDS patients (n=21) showed that a home exercise intervention had 71% retention and was associated with significant improvements in 6 min walk distance.17 Furthermore, in a feasibility RCT of exercise delivered before admission, during the inpatient stay and after discharge vs control in people with planned allo-HSCT (n=30), recruitment and retention rates were 20% and 33% (respectively) and a significant improvement in 6 min walk test distance was observed in the exercise group.18 However, the previous evidence is limited to studies conducted during induction chemotherapy and not rehabilitation intervention,16 17 and were exercise-only interventions (ie, not multidisciplinary).1618 Assessing multidisciplinary prehabilitation strategies becomes crucial to pre-emptively counter the physical decline experienced during allo-HCST among AML and MDS patients to potentially mitigate the impact of treatment on patients’ overall health and well-being. Furthermore, incorporating a comprehensive prehabilitation approach appears important for addressing the physical decline during allo-HCST among AML and MDS patients and minimising the potential negative impacts on psychological and psychosocial functioning, promoting a holistic enhancement of patients’ overall health and well-being.

This study aims to investigate the feasibility, safety and preliminary efficacy of multidisciplinary prehabilitation in adults offered allo-HSCT. Feasibility will be assessed in terms of intervention uptake, retention, adherence and acceptability to patients/families/allied health practitioners. Safety will be evaluated in terms of adverse events. The trial will also assess whether multidisciplinary prehabilitation is associated with improvements in functional capacity and psychosocial outcomes.

Methods

Patient and public involvement

Patients and the public were not involved in the development of this protocol or study design. Eligible patients will be recruited into the study as study participants (described below). Participants will be informed when the study is published through direct communication, such as emails and letters, providing them with details about where and how to access the published findings.

Ethics approval for this study has been provided by the Central Adelaide Local Health Network (HREC 2022/HRE00284). Recruitment for the study commenced in June 2023 and will continue until July 2024. The methods have been designed and are reported according to the SPIRIT and CONSORT-pilot study checklist.19 The intervention is described according to the TIDieR checklist.20

Study setting and clinical context

This study will be conducted by the Cancer Allied Health team at the Royal Adelaide Hospital (RAH). The RAH is a public hospital located in Adelaide, South Australia. The RAH cancer centre provides medical oncology, radiotherapy/brachytherapy, and malignant and non-malignant haematology. It is also the state-wide hub for complex cancers and stem cell transplant. Currently, there is no multidisciplinary prehabilitation service within the cancer centre at the RAH.

Treatment of AML and MDS typically involves a multifaceted approach. For AML, standard treatment begins with chemotherapy, divided into induction therapy to induce remission by killing leukaemia cells, and consolidation therapy to eliminate any remaining cells and prevent relapse.21 In contrast, for MDS, hypomethylating agents like azacitidine and decitabine are more commonly used, serving to manage the disease rather than cure it.22 These agents can improve blood counts and delay progression to AML but are not typically curative.23 Bone marrow transplant (BMT), particularly allogeneic transplant, offers the only potential cure for both AML and MDS. However, it is a high-risk procedure and not suitable for all patients. The percentage of patients proceeding to transplant varies; it is more common in younger patients or those with high-risk disease profiles. While BMT can be curative, it is important to note that this is not the case for all patients. Success rates vary based on factors like patient age, overall health and disease stage. For instance, in AML, the curative potential of BMT is significant, but it comes with risks such as graft-versus-host disease. The decision to proceed with BMT is based on a careful assessment of these risks against the potential benefits for each individual patient.

Study design

The study is a single-group 8-week pre-post feasibility study. The primary outcomes are feasibility (assessed based on intervention uptake, retention, adherence and acceptability) and safety. Additional outcomes include pre-intervention and post-intervention assessments of leg strength, upper-body strength, aerobic fitness, falls risk, anthropometry, nutritional status, quality of life, anxiety, depression, self-efficacy for coping with cancer, and distress. Hospital-acquired complications and length of stay will also be assessed post-discharge from transplant. Figure 1 shows a flowchart of the study design. If the intervention is feasible, this study will provide key findings to inform a future large-scale randomised controlled trial, and provide information required to underpin ongoing prehabilitation for allo-HSCT participants. Furthermore, this innovative model of multidisciplinary prehabilitation has strong potential to be adapted for other patient populations across the cancer intervention at the RAH.

Figure 1 Study flow. 2MST, 2-minute step test; Ax, assessment; BIS, bioimpedance spectroscopy assessment; CBI, Cancer Behaviour Inventory; EORTC-QLQC30, core quality of life questionnaire; F2F, face-to-face; HADS, Hospital Anxiety and Depression Scale; HACS, hospital-acquired complications; OT, occupational therapy; PG-SGA, Patient-Generated Subjective Global Assessment; STS, sit-to-stand test; TH, telehealth; TUG, timed up and go test.

Recruitment, screening and informed consent

Potential participants will be identified by the AML/MDS multidisciplinary team, transplant multidisciplinary team and the MDS/AML nurse consultant (or haematologist or other members of the treating team) and screened for eligibility. To ensure accurate measurement of uptake, the study team is involving multiple clinical teams, nurse consultants and treating haematologists to identify and refer all potential allo-HSCT candidates for screening against the eligibility criteria. Treatment pathways of eligible AML/MDS patients are tracked in a REDCap database to ensure accurate measurement of uptake. This broad, multidisciplinary approach aims to capture all eligible participants across different care pathways leading to allo-HSCT. All eligible participants will provide informed written consent prior to enrollment in the study.

Participants

Inclusion criteria

To be eligible for participation, individuals must be (i) 18 years or older, (ii) diagnosed with AML or MDS, (iii) offered allo-HSCT at the RAH, (iv) medically stable based on guidelines for exercise24 25 and (v) have clearance from their consultant haematologist.

Exclusion criteria

Individuals will be ineligible if they either (i) have cognitive impairment severe enough to restrict participation in the intervention or provide informed consent, (ii) have any absolute contraindications to exercise as indicated in written medical clearance (eg, unstable angina or uncontrolled heart failure) or (iii) if they have a permanent pacemaker, which will preclude participation in bioimpedance spectroscopy. If the timeline to transplant is known to be less than 8 weeks, these participants may be deemed ineligible for the study. However, if the timeline to transplant is unclear or unknown at the time of recruitment, then participants may receive less than the 8-week intervention if their transplant is scheduled sooner than anticipated. We will be documenting length of intervention provided if shorter than the planned 8 weeks and will also document if participants are screened as ineligible due to inefficient time to intervene.

Multidisciplinary Prehabilitation intervention overview

The prehabilitation intervention, beginning post-induction chemotherapy and post-remission/transplant scheduling for allo-HSCT patients, spans 8 weeks and encompasses exercise, nutritional, psychosocial and psychological assessments. Tailored to the diverse needs of AML/MDS patients undergoing various treatments, this programme systematically integrates each care component. Adherence calculations will objectively assess participant engagement, while standard care from allied health staff, including social work, physiotherapy, occupational therapy, exercise physiology and psychology services, is available throughout the project. The unique feature of the programme is its methodical introduction of these services at an earlier stage in the treatment process, providing a proactive and comprehensive support approach that has the potential to improve patient outcomes compared with conventional practices. Incorporating the COM-B model’s (capability, opportunity, motivation and behavior)26 framework, our multidisciplinary prehabilitation intervention is designed to address and enhance participants’ capability (by providing knowledge and skills through tailored exercise, nutritional guidance and psychological support), opportunity (by creating a supportive environment through supervised sessions and social support) and motivation (through personalised goal-setting and feedback). The intervention components are described in table 1.

Table 1 Overview of the interventions

Intervention	Details	
Exercise	Supervised sessions occur biweekly for 8 weeks (total of 16 sessions) led by an accredited exercise physiologist/physiotherapist. Guided by national and international recommendations for cancer patients involving 6–8 resistance exercises and 20–40 mins of aerobic exercise. Adaptable to individual capabilities. Safety protocols and vital checks integrated. Electronic recording of exercise prescription and adherence evaluation through clinician notes.	
Dietetics	Offers a 45–60 min face-to-face initial assessment for nutritional status. Provides pre-transplant education focusing on strategies to enhance or maintain nutrition, addressing food safety guidelines and a high-energy, high-protein diet to minimise weight loss. Follow-up phone/telehealth check-in for at-risk participants post-assessment. Naso-enteric feeding post-haematopoietic stem cell transplantation.	
Social work	Provides initial education on legal matters (Wills, Power of Attorney, Advanced Care Directive) and financial support. Delivers a resource pack and offers a follow-up appointment for addressing queries or document completion. References include specific legal and financial service links.	
Occupational therapy	Conducts a 60-min session (face-to-face/phone/telehealth) encompassing assessment, intervention and education. Assesses personal, environmental and occupational barriers and identifies equipment or service needs. Focuses on fatigue education and provides a cancer-related fatigue education booklet for patient take-home.	
Psychology	Provides a single 60–90 min face-to-face psychoeducation session during weeks 6–8, offering strategies to cope with the emotional impact of stem cell transplants. Topics covered include mood and anxiety management, coping strategies during hospital admission and social support. Distributes a booklet for coping skills.	

Exercise intervention

Participants will undergo two supervised face-to-face 60 min exercise sessions weekly for 8 weeks, totalling 16 sessions. These may take place in the RAH gymnasium, on the ward or via telehealth, supervised by an experienced exercise physiologist/physiotherapist. The exercise regimen, aligned with national and international cancer guidelines,25 27 includes 6–8 resistance exercises plus 20 min of aerobic exercise each session. Resistance exercises involve free weights, body weight, resistance bands and machines (2–3 sets, 8–12 reps per exercise). Aerobic exercise includes treadmill walking/jogging or cycling, targeting an intensity of 12–14 RPE on the Borg Scale. The exercise will be individualised and progressive, and individual modifications will be made based on participants’ abilities or treatment-related effects. Where appropriate, participants will be advised to maintain regular physical activity between the two supervised sessions, aiming to meet the national physical activity guidelines for their age group and health status.25 27 Individual modifications will be made based on participants’ abilities or treatment-related effects. Throughout the intervention, adverse events will be continuously monitored per the Common Terminology Criteria for Adverse Events (CTCAE V.6),28 categorising events from grade 1 (asymptomatic or mild symptoms) to grade 5 (death). Serious adverse events will encompass instances requiring hospitalisation, resulting in significant disability, posing life-threatening risks or leading to death. Electronic records will be used to document exercise prescriptions, and clinician field notes will be used to capture information relevant to feasibility, safety and adherence throughout the study.

Dietetics

Participants will complete a face-to-face dietetic assessment prior to the start of the exercise intervention. The 60-min session is an adapted version of a standard dietetic initial consult, gathering information on anthropometrics, treatment-related side effects that may impact oral intake and diet history. Dietetics will also determine participants’ nutritional status using the Patient-Generated Subjective Global Assessment (PG-SGA)29 and body composition using bioimpedance spectroscopy.30 31 All participants will receive nutritional education on high-protein and high-energy diet, and recipes for high-protein drinks. Participants identified as malnourished or at risk will be provided with individualised nutrition advice and follow-up as required. After completing the exercise intervention, participants will be re-assessed using the PG-SGA and bioimpedance spectroscopy. Electronic records will document PG-SGA score, bioimpedance spectroscopy measures, and nutrition advice and education.

Social work

The social work service offers therapeutic interventions, including face-to-face initial psychosocial assessments and solution-focused practices, supporting participants and families in their stem cell transplant journey. Two to 4 weeks into the intervention, a single 45–60 min face-to-face education session will cover important legal and financial aspects, including Wills, Enduring Power of Attorney, Advanced Care Directive, Centrelink, Superannuation, financial counselling and carer support. Information is sourced from specific documents and websites. After the session, participants receive a pack with the discussed legal documents and contact numbers. A 30-min face-to-face follow-up at weeks 6–8 addresses questions and concerns.

Occupational Therapy

Occupational therapy (OT) input, delivered in a face-to-face 60 min session via phone, comprises education, assessment and intervention components. The assessment is an adapted version of the standard Central Adelaide Local Health Network acute OT initial assessment, gathering information on social history, environmental factors, physical and cognitive functional status, and identifying barriers, risks and functional changes. The intervention includes equipment provision, task adaptation, referrals to other allied health disciplines or external agencies, and communication with the inpatient OT team for high-risk patient follow-up. The educational component focuses on cancer-related fatigue and is delivered through a discussion and tailored education using a booklet. The entire OT process aims to be completed in weeks 1–3 in a single session.

Psychology

Participants will attend a 60–90-min face-to-face psychology education session in weeks 6–8, focusing on psychoeducation and coping strategies for their planned stem cell transplant. Topics covered include the emotional impact of transplant, mood management, anxiety management strategies and practical coping skills for their admission and participants receive educational handouts related to coping skills.

Procedure

Assessments

Data, collected at baseline, post-intervention and post-transplant, will evaluate intervention feasibility (uptake, retention, adherence, acceptability) and safety (adverse events). Patient outcomes (physical, psychosocial) will be measured during a 60-min visit at RAH, with hospital-related outcomes post-transplant. Assessments conducted by trained allied health professionals. If a patient’s transplant is delayed beyond the planned 8 weeks, their participation in the prehabilitation programme would be adjusted accordingly. The 8-week assessment would still be completed, and the patient would then access usual care from physio, social work, psychology and OT prior to transplant. If the 8-week period is shortened, we complete the follow-up assessment as required (ie, prior to the 8-week mark), noting the number of sessions completed and the length of the study intervention.

Study measures

An overview of the study flow and all study measures is shown in figure 1.

Primary outcome measures

Feasibility

Intervention feasibility will be evaluated based on (1) intervention uptake, (2) retention, (3) adherence and (4) acceptability:

Intervention uptake, determined as the percentage of eligible potential participants approached vs the number of participants enrolled into the prehabilitation intervention.

Retention, determined as the percentage of enrolled participants who complete the 8-week study.

Adherence, determined as the number of sessions attended vs the number of sessions prescribed.

Acceptability of the prehabilitation intervention to participants/families/health staff will be assessed using a survey administered at the end of the 8-week prehabilitation intervention. The 5-item survey assesses perceptions of enjoyment, self-efficacy, intent for future participation, and appropriateness of session frequency and duration on a 5-point Likert scale, also including an open-ended response section for participants to provide qualitative feedback. Additionally, detailed information on the acceptability component from the medical, nursing and allied health feasibility.

Safety

Safety will be assessed based on the number, grade and causality of adverse events (this will be graded via the CTCAE [24] and monitored and recorded throughout the prehabilitation intervention). The CTCAE is a standard classification system for reporting adverse events in cancer trials, enabling unified grading and comparisons across studies. Adverse event severity and causality will be assessed using the following severity grades: grade 1 (mild symptoms), grade 2 (moderate symptoms), grade 3 (severe symptoms, not immediately life-threatening), grade 4 (life-threatening symptoms) and grade 5 (death). The causality of these events with the exercise component of the intervention will be categorised as certain, probable, possible or unlikely.

Secondary outcome measures

Physical and psychosocial outcomes will be assessed at baseline and immediately following the 8-week intervention:

Leg strength: leg strength will be assessed using the 30 s chair stand. The test involves recording the number of times a person can stand up from a chair and sit back down again in 30 s and has been found to be a valid and reliable tool for assessing lower extremity strength in cancer patients.32 33

Upper-body strength: upper-body strength will be assessed with grip strength using a Jamar hand dynamometer (Jamar Corp., Duluth, MN, USA), with participants holding their arm with their elbow bent at a 90 degree angle and squeezing the dynamometer as hard as possible. The Jamar hand dynamometer is a widely used instrument with established test-retest, inter-rater and intra-rater reliability among cancer survivors.34

Aerobic fitness: aerobic fitness will be assessed using the 2-min step test. The test requires the individual to march in place as fast as possible for 2 min while lifting their knees to a height midway between their patella and iliac crest when standing.35 The test is valid and has shown to have excellent test-retest and inter-rater reliability, and strong correlations with other functional capacity measures in various clinical and non-clinical populations.36 37

Falls risk: the timed up and go test assesses mobility by timing how quickly an individual can stand up, walk 3 m, turn, return and sit down, with shorter times indicate better functional mobility. The test is considered a valid and reliable test for assessing physical function and identifying falls risk in community-dwelling older adults.38 39

Body composition and anthropometrics: body composition (fat-free mass and fat mass) will be analysed using multifrequency bioimpedance spectroscopy (ImpediMed Ltd., Australia), which uses multiple frequencies of electrical currents to assess body composition.30 31 This involves attaching four electrodes (two to the left hand and two to the left foot) with the participant in a supine position. This method has been shown to be valid and reliable for assessing body composition in clinical populations.30 31

Nutritional assessment: nutritional assessment will be assessed by a dietitian experienced at using the PG-SGA tool.29 A global rating of nutritional status (well nourished, suspected or moderately malnourished or severely malnourished) and an overall PG-SGA numerical score will be calculated.

Quality of life: the European Organisation for Research and Treatment of Cancer Care Quality of Life Questionnaire (EORTC QLQ C30): the EORTC QLQ-C30 is a 30-item scale that measures quality of life in cancer patients who receive scores for functional scale (15 items), symptom scale (13 items) and global health status (2 items). Each item is rated on a scale from 0 (not at all) to 4 (very much). High scores for functional and global health scales indicate a good quality of life, while high scores in symptom scale represent a high level of problems.40

Anxiety and depression: the Hospital Anxiety and Depression Scale (HADS): the Hospital Anxiety and Depression Scale (HADS) is a reliable and valid questionnaire41 for hospitalised populations, consisting of 14 total questions (rated 0, 1, 2 and 3) related to anxiety and depression.

Self-efficacy: the Cancer Behaviour Inventory-Brief Version is a valid measure of self-efficacy for coping with cancer consisting of 12 items.42

Hospital-related outcomes: hospital-acquired complications and length of stay will be assessed post-discharge from transplantation. Data on hospital-related outcomes will be collected through case note review and hospital database to determine length of stay and hospital-acquired complications for each patient. Medical records will be assessed to verify cancer type, date of diagnosis and treatment details. Length of stay and complications arising from transplantation will be accessed retrospectively, post-hospitalisation.

Analysis

Sample size

We plan to recruit 20 participants into this study. Assuming 50% of participants will be deemed elligible/medically cleared for participation in the study, and based on annual case numbers managed at the RAH. As the primary endpoint of this study is to assess the feasibility, an a priori power calculation was not performed.43 The target sample size of 20 will be sufficient to address the research aims regarding feasibility and will provide preliminary evidence on the safety and efficacy of the prehabilitation intervention. Data obtained from this feasibility study will be used to inform clinical practice for the implementation of a multidisciplinary prehabilitation programme at the RAH, as well as power calculations and sample size for a subsequent, adequately powered RCT. To mitigate potential high dropout rates, the study will employ several strategies to maximise participant engagement and retention, such as flexible scheduling of intervention sessions, telehealth options, involving caregivers/family for support, frequent check-ins, and tailoring components to individuals’ specific needs and circumstances.

Data analysis

Participant baseline characteristics will be reported using means and SD for continuous outcomes or counts and percentages for categorical outcomes. The feasibility of the intervention will be evaluated based on uptake, retention and adherence rates, all expressed as percentages, as well as acceptability. The prehabilitation intervention will be deemed as feasible if uptake, retention and adherence rates achieve a pre-defined rate of 50% or higher.44 45 The analysis of acceptability data will involve quantitative assessment of Likert scale responses from a 5-item survey, exploring enjoyment, self-efficacy, future participation intent and session appropriateness. Intervention acceptability will be determined based on thematic analysis of qualitative feedback, and descriptive analysis of overall ratings. Qualitative feedback obtained from the participant and allied health feasibility questonnaires will undergo thematic analysis to identify recurring themes and patterns related to enjoyment, self-efficacy, future participation intent and session appropriateness. This qualitative analysis, in conjunction with quantitative assessment of Likert scale responses, will offer a comprehensive understanding of intervention acceptability. Safety will be assessed based on the number, grade and causality of adverse events (this will be graded via the CTCAE and will be monitored and recorded throughout the prehabilitation intervention). The intervention will be considered safe if there are no grade 4 or grade 5 adverse events occurring as a direct result of participation in the prehabilitation programme. Data will be analysed descriptively to summarise the frequency of complications and the range and mean of length of stay.

Due to the study’s underpowered nature, the analysis of preliminary efficacy outcomes will be reported in terms of the estimated effect sizes and their 95% CIs. All analyses will be undertaken using Stata/MP (v16, Stata Corp, College Station, TX, USA).

Discussion

This study addresses a critical gap in the care of patients undergoing allo-HSCT. Allo-HSCT is a complex and intensive treatment with substantial physical, psychosocial and psychological impacts on patients.4 The current absence of a multidisciplinary prehabilitation service specifically tailored for allo-HSCT patients at the RAH underscores the potential importance of this study. The clinical significance of implementing an intensive prehabilitation intervention in this context lies in its potential to enhance the overall well-being and functional capacity of patients preparing for allo-HSCT. The unique challenges posed by the treatment, such as prolonged hospitalisation, potential complications and the intricate interplay of physical and psychological stressors, necessitate a comprehensive and tailored approach to patient care. By introducing a multidisciplinary prehabilitation programme, this study aims to address these challenges and ultimately improve patient outcomes.

The existing literature highlights the limited number of studies investigating the effect of exercise interventions in AML and MDS patients prior to allo-HSCT.1618 In studies focusing on exercise interventions, Kuehl et al46 evaluated the feasibility and efficacy of high-intensity interval training and resistance exercise before allo-HSCT, noting a low recruitment rate that limits immediate applicability. Potiaumpai et al47 investigated a resistance training programme before HSCT, reporting 83% acceptability, 92% adherence and no exercise-related adverse events, with significant performance improvements in the exercise group. Wood et al48 examined a 5-week to 12-week home-based aerobic exercise intervention in allo-HSCT candidates, finding no significant differences in VO2peak or 6MWD between groups due to small sample size, suggesting improvements for future study design. Together, these studies highlight the potential benefits of structured exercise interventions pre-HSCT, while emphasising feasibility considerations. Our research project aims to extend these findings by assessing the impact of multidisciplinary prehabilitation strategies on AML and MDS patients prior to allo-HSCT. This study will address the need to pre-emptively counter the physical decline experienced during allo-HSCT, potentially mitigating the impact of treatment on patients’ overall health and well-being. By focusing on prehabilitation interventions, our research seeks to provide valuable insights into optimising patient care and outcomes in this specific context, contributing to the development of evidence-based clinical guidelines and best practices. The anticipated clinical implications of this study are far-reaching, offering prospects for significant advancements in the care of patients undergoing allo-HSCT. Successful implementation of the multidisciplinary prehabilitation intervention has the potential to substantially improve patient outcomes in several key areas. First, by focusing on feasibility, safety and adherence, the study lays the groundwork for establishing the efficacy of the intervention in subsequent large-scale randomised controlled trials. Enhanced feasibility and safety may translate into tangible benefits for patients, potentially reducing complications, shortening hospital stays and, ultimately, enhancing overall quality of life.

The incorporation of exercise, nutritional support, psychological and psychosocial interventions during the pre-transplant phase is expected to contribute to a more robust and resilient patient. This, in turn, could lead to a smoother recovery trajectory post-transplant, addressing the protracted recovery period that allo-HSCT patients often experience. The tailored approach to interventions, specifically directed towards AML or MDS patients, underscores a nuanced understanding of the diverse characteristics within the broader allo-HSCT population. This targeted strategy allows for interventions to be precisely aligned with the unique needs of this subgroup, potentially maximising the impact on their care. Furthermore, the innovative aspect of this study lies in its multidisciplinary approach to prehabilitation. By integrating exercise, nutrition, psychology, social work and occupational therapy, the study acknowledges the multifaceted nature of allo-HSCT care. The success of this approach may serve as an innovative model for integrating allied health disciplines into a cohesive and patient-centred prehabilitation service, benefiting allo-HSCT patients and potentially applicable to other patient populations within the cancer centre at RAH. Future research should also explore innovative delivery models that optimise the cost-effectiveness and scalability of multidisciplinary prehabilitation interventions, ensuring broader accessibility across diverse healthcare settings. In essence, the potential clinical implications of this study extend beyond its immediate focus, offering a framework for the broader enhancement of patient care strategies in cancer interventions.

Strength and limitations

One notable strength of this study is its comprehensive and multidisciplinary approach, encompassing physical and psychosocial care aspects for allo-HSCT patients. By addressing factors such as leg and upper-body strength, anxiety, depression and self-efficacy, the study acknowledges the holistic needs of these individuals, contributing to societal benefits by fostering financial stability through improved physical abilities, enhancing familial relationships through increased emotional well-being and supporting legal well-being by promoting overall mental health and self-confidence. Another significant strength lies in the primary focus on feasibility, recognising the practical challenges of implementing the prehabilitation intervention in a real-world setting. This emphasis enhances the study’s ability to inform future clinical practice and assess its potential scalability. Additionally, involving patient partners in the research team or establishing a patient advisory committee would be beneficial for interpreting results and guiding subsequent actions. The targeted inclusion criteria, specifically focusing on AML or MDS patients offered allo-HSCT, add precision to participant selection and enhance the study’s relevance to this patient population. Moreover, the potential for generalisation of the multidisciplinary prehabilitation model beyond allo-HSCT patients, if successful, adds to the overall strength and applicability of the study. Limitations include the study’s reliance on a single-group design, which means that study outcomes cannot be directly attributed to the prehabilitation intervention. Furthermore, the relatively small sample size, while adequate for assessing feasibility, may limit the generalisability of findings and hinder the detection of smaller yet potentially significant effects. The short duration of follow-up, focusing on immediate post-transplant outcomes and an 8-week intervention period, might not fully capture the long-term impacts of prehabilitation. Furthermore, it remains important for future research to assess outcomes post-transplant. To assess the sustainability of observed benefits, a longer follow-up period would be necessary. It is also important to consider that acceptability assessment relies solely on the 5-item survey, which may not capture detailed responses necessary for thorough thematic analysis. Future research should consider incorporating in-depth qualitative interviews to provide richer insights into acceptability, aiding in the optimisation of intervention strategies and study methods. These limitations should be acknowledged in interpreting the study’s findings and in considering its broader implications.

Conclusion

This study addresses a critical need for individualised, multidisciplinary prehabilitation services for allo-HSCT patients at RAH. The potential clinical implications of a successful intervention are substantial, offering improved patient outcomes and informing multidisciplinary care models. The study’s strengths lie in its comprehensive multidisciplinary approach, feasibility focus, targeted patient population and potential for generalisation. However, limitations, including the single-group design, small sample size and short duration of follow-up, should be acknowledged. The findings of this study have the potential to contribute significantly to the evolving field of prehabilitation and shape the future care for allo-HSCT patients and potentially other cancer patient populations at RAH.

Data availability statement

No data are available.

Review Process File
05 09 2024

Funding: CM is supported by a Medical Research Future Fund Emerging Leader Grant (GNT1193862).

Prepublication history for this paper is available online. To view these files, please visit the journal online (https://doi.org/10.1136/bmjopen-2024-084372).

Data availability free text: This is a protocol and no data has been collected yet.

Patient consent for publication: Not applicable.

Provenance and peer review: Not commissioned; externally peer reviewed.

Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
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