The 4‘I’s for a holistic musculoskeletal rehabilitation approach following hematopoietic stem cell transplantation

Introduction

The clinicians working with haematopoietic cell transplantation (HCT) patients must have first-hand knowledge of potential musculoskeletal and systemic complications post-HCT. This is important not only for a better understanding of the disease process but also for planning and implementing a holistic, focused, and appropriate physical/functional examination which reflects the complex presentation of fascia, muscle, joint, and skin involvement [1]. Patients with HCT may present with a wide variety of neuromuscular complications such as polyneuropathy, myopathy, polymyositis, and myasthenia gravis [2]. Furthermore, chronic graft-versus-host disease (cGvHD) is known to affect various organs in the body, such as liver, heart, lungs, reproductive organs, and skin. However, musculoskeletal cGvHD can also result in muscle weakness, musclular pain, muscle tenderness, arthralgia, and oedema, thus resulting in reduced function, mobility, and poor quality of life [3].

Due to the complex nature of musculoskeletal manifestations, a unique individual approach is required, with respect to the physical and functional evaluation of HCT patients, as well as when designing their rehabilitation programs. To help approaching this topic, we introduce the following 4 ‘I’s:
1. Importance of individualized global functional evaluation during HCT physical/ functional assessment,
2. Importance of individualized bespoke exercise rehab prescription for patients that is aimed at optimal gains,
3. Importance of knowledge on drug-drug interactions and pharmacodynamic and its impact on patient recovery and rehab,
4. The importance of having a deeper understanding of patients and caregivers’ perspectives when it comes to what patients mean about quality of life (QoL), and the need for a dedicated HCT case worker to help facilitate patients’ journey during and after the HCT.

Importance of individualised global functional evaluation

It is very important and vital to acknowledge that most patients post-HCT and bearers of CGvHD suffer from multi-joint/fascia/skin complications, and this needs to be addressed in the very early stages of rehabilitation assessment if we are to capture the true functional capacity of the patients.

A case study of a 14-year-old female patient [1] is a classic example which highlights the importance of a holistic and global functional evaluation approach when conducting physical and functional evaluations. As reported in this case, the patient developed severe GvHD of multiple organs post-HCT, with lower limbs affected, having been referred to physical therapy for ankle joint lesion which impacted her gait and mobility. On examination, the patient had extensive poikiloderma and scleroderma affecting over 70% of the skin surface and bilateral Achilles tendinitis. On further evaluation, when the general assessment rule was followed, the patient was found to have upper limb weakness in the grips and loss of hip joint movement affecting gait and mobility, thus prompting further investigations for hip joint pathology which revealed early avascular necrosis of the hips. Upper and lower limb weakness due to polymyositis secondary to cGvHD has been reported previously, resulting in diffuse, generalised myopathy with preserved sensitivity but elevated CPK and aldolase [4].

Skin and the associated fascia are among the main organs that can have a major influence on functional limitations. Deep sclerosis or fasciitis at the skin or overlying joints (superficial sclerosis) may occur with or without superficial sclerosis, whereas isolated fasciitis can cause reduced joint function stiffness, and the overlying skin can remain unaffected [4]. Understanding the role of fascia and its implications is important for clinicians since it may influence the way we capture both static and dynamic movements. A demonstration of functional movement captured in patients with upper-limb GvHD affecting the fascia is presented in Fig. 1 and Fig. 2. Wrist extension which was limited to 10° when the fingers were extended, showed a significant increase when captured with fingers in flexion [1], thus reflecting the role of fascia and short- and long-lever measurements.

Importance of individualized exercise rehab administration

There are growing calls on the need for individualized exercise prescription approach in this patient group and growing concerns about the concept of “One size fits for all”. As for HCT rehabilitation team, it is important to look closely and have a deeper understanding of individual patients’ disease processes, comorbidities, pre-existing and developing physical and functional limitations, psychological status, drug regimens, and their interaction/side effects in order to deve-lop a holistic rehabilitation program.

Several studies have supported the role of exercise post-HCT and in the course of GvHD, with certain benefits such as increased endurance, better psychological well-being, reduced anxiety and depression, immune cell recovery, higher blood hemoglobin levels, improved cardiovascular and respiratory functions, enhanced physical function, increased activities of daily life, and better quality of life [6-9]. However, many published studies seem to use common exercise approaches which lack individualisation in exercise prescription, and failed to follow a structured exercise progression methodology aimed at optimal benefits for patients.

As explained by Kraemer et al. [10], resistance training itself does not ensure optimal gains in muscle strength and performance. Rather, it is the magnitude of the individual effort and systematic structuring of the training stimulus that ultimately determine the outcomes associated with resistance training. Being the rehabilitation specialists, we must implement the principles and scientific approach to exercise prescription where the right dosage of the right exercise applied at the right time for the right patient, is used in the presence of the specific patient pathology, aimed at targeted management of the impairments by implementing the principles of specificity, dosing regimens, optimal loads, and taking contextual factors into account [11]. In a recently published review on exercise prescription practices in patients we have revealed that the majority of studies did not use the scientific basis of exercise prescription when designing rehabilitation programs for this group of patients [12].

Importance of knowledge on pharmacodynamics and its impact on rehab practice

Vital significance of drug-drug interactions and pharmacodynamics in HCT/GvHD patients is widely understood by clinicians, due to its potential impact on rehabilitation and possible masquerading of neuromusculoskeletal symptoms. The majority of HCT/GvHD patients are receiving a cocktail of drugs which may have a significant impact on musculoskeletal performance. For example, Fuji et al. [13] presented a case of a patient with severe fatigue and spontaneous pain localised to the lower part of the right leg. The symptoms then progressed to intolerable itching in both lower limbs spreading to genital area with associated hyperesthesia and electric shock-like pain, even at very light touch. On day 20, the symptoms changed to excruciating tingling pain in both thighs. Interestingly, no pathological changes were observed on magnetic resonance imaging (MRI) of the brain and spinal cord, and radiography, computed tomography, MRI. Bone scintigraphy of spine and lower limbs showed no abnormalities. The patient was diagnosed with chronic regional pain syndrome. However, this case highlights the importance of drug-induced complications. The patient was treated with intravenous methotrexate on days 1, 3, and 6, and tacrolimus was administered via continuous intravenous infusion starting on day 1. By reducing the dosage of cyclosporine, significant relief of these symptoms was achieved.

Similarly, Collini et al. [14] reported patients with progressive joint pain in the ankles, knees, feet, and hands. Therefore, the patient had to use crutches to walk. This condition was managed by discontinuation of tacrolimus treatment. Finally, Varma et al. [15] have also published clinical cases where the patients experienced pain in both lower extremities of 10/10 on the VAS scale, worsened movements in lower limbs with normal appearance upon examination. High doses of opioids did not alleviate the pain syndrome. However, on day +4 post allo-HCT, intravenous tacrolimus was discontinued thus allowing pain management. A review of HCT/GvHD drugs and their impact on patients’ neuromusculoskeletal symptoms has also been published elsewhere [16].

Importance of understanding the patient’s and caregivers perspectives for quality of life

Healthcare organisations are responsible for the arrangement of appropriate post-HCT care and should acknowledge that this care will differ from patient to patient and concern the potential impact on patients’ families and caregivers [17]. With respect to clinicians, patients, and their caregivers, it is evident that the majority of HCT patients needs a long-term follow-up on an outpatient basis, looking at various aspects of their recovery including activities of daily life, return to work or school/sports, and monitoring complications. Thus, the whole process is a massive journey from A to B to C [18]. Patients are often seen at regular intervals and then referred to other consulting specialties for checkups and treatment arrangement. Since chronic GvHD may develop even years after transplantation, current guidelines recommend an ambulant follow-up for HCT patients up to 18 months posttransplant when possible.

Figure 3. HSCT Hexagon

Furthermore, we recommend the Hexagon concept (Fig. 3) which proposes that each transplant centre should have a dedicated HCT case manager who collects information on the patient’s condition, coordinates individualised rehabilitation efforts, and assists with improvement of patient’s and caregiver perspectives in cases of late HCT complications as well as primary and chronic GvHD manifestations [17]. On this basis, we also advocate the development and implementation of an extended clinical role ‘Advance Clinical Practitioner in HCT Rehabilitation’ (ACP-HCT). This role would be carried out by healthcare professionals who have the most contact with this patient group.

In the UK, it could be a physiotherapist or nurse whose advanced clinical practice has already been implemented in various fields, including musculoskeletal problems [19]. This ACP-HCT will be responsible for overseeing the patient’s journey from pre-transplant to up to 3 years and will have extended training and skills to be able of acting as first-contact clinicians for post-HCT patient care, i.e., a role similar to that of first-contact practitioners in the National Health Service (NHS) [20]. The ACP-HCT can not only help in the early detection of complications but can also promote timely care to patients and facilitate their future journey. The ACP-HCT will be able to refer the patients for appropriate blood tests and radiology, to discuss the findings with the HCT consultant, and also refer the patient to appropriate special departments including orthopaedics, dermatology, neurology, gynaecology, and rheumatology.

The clinician will also be able to interact with consultants in order to discuss probable tapering of drugs if drug-induced neuromusculoskeletal complications have been identified, by contacting physiotherapists, rehabilitation teams, and occupational therapists advising them on rehabilitation plans.

We would recommend a recent consensus paper on physical therapy in HCT patients by the working parties from the American Society for Transplantation and Cellular Therapy, the Eastern Mediterranean Blood and Marrow Transplantation, and the European Society for Blood and Marrow Transplantation which offers the best practice guidelines for managing patients with HCT [21].

Conclusion

Patients with HCT and caregivers fight a difficult battle against primary disease or treatment-induced complications. Their anxiety and stress may be even worse due to suboptimal care, lack of defined pathways, poor communication, and confusion caused by conflicting advice provided by clinicians. Furthermore, there appears to be a skill difference between the rehabilitation clinicians, due to lack of knowledge for various aspects of disease, treatment modes, and complications which may be attributed to a lack of structured professional development plans, scope of practice profiles, and lack of appropriate continuous training in the field.

The current study highlights the areas of improvement in the delivery of post-HCT services which can be used by both policymakers and clinicians to help enhance services and patient experience.

In summary, this exhaustive investigation aims to supply the healthcare providers specializing in HCT rehabilitation with profound understanding and detailed insights into the difficulties of rehabilitation in this unique context. The detailed roadmap seeks for both informing and empowering the fellow practitioners with the knowledge and insights needed to make a meaningful impact on the life quality of patients undergoing allogeneic stem cell transplantation.

Conflict of interest

None declared.

References

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