The role of physical therapy across the transplant trajectory in allogeneic hematopoietic stem cell transplantation, a systematic review and clinical framework

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) increasingly involves older and medically complex patients, in whom impaired pulmonary function and high comorbidity burden adversely affect survival and long-term outcomes. Rehabilitation and exercise interventions are biologically plausible strategies to mitigate deconditioning along the transplant trajectory, but their role in allo-HSCT has not been systematically organised within a phase-specific clinical framework. Methods: A systematic review of randomised controlled trials (RCTs) was conducted according to Cochrane guidance and PRISMA 2020, with prospective registration in PROSPERO. PubMed, Embase, PEDro, Web of Science, CENTRAL and Scopus were searched from inception to early 2025, with an updated PubMed search later in 2025. RCTs evaluating any rehabilitative or exercise-based intervention in adults undergoing allo-HSCT in the pre-transplant, peri-transplant or post-transplant phase were included. Outcomes comprised physical function and exercise capacity, respiratory function, health-related quality of life, fatigue and, when reported, transplant-related endpoints. Risk of bias was assessed with RoB 2 and certainty of evidence with GRADE. Results: Ten RCTs (537 participants; 405 completers) met inclusion criteria. Interventions were categorised as respiratory physiotherapy (pre-transplant), supervised multimodal exercise and whole-body vibration (peri-transplant) and combined supervised/home-based programmes or vibration-supported regimens (post-transplant). Pre-transplant inspiratory and respiratory training improved respiratory muscle strength and six-minute walk distance in small trials, with mixed effects on spirometric indices. During hospitalisation, supervised multimodal exercise attenuated declines in aerobic capacity and muscle strength compared with standard care, whereas effects on fatigue and quality of life were heterogeneous. Post-transplant interventions confirmed the feasibility and safety of supervised and partly home-based programmes, but benefits in mobility, fatigue and quality of life were modest and heavily dependent on adherence. No trial was powered to demonstrate effects on transplant-related mortality, survival or graft-versus-host disease, and representation of patients older than 55 years was limited. Overall, 70% of trials were judged at high risk of bias and GRADE certainty ranged from low to very low particularly for whole-body vibration and patient-reported outcomes. Conclusions: Available RCTs suggest that rehabilitation across the allo-HSCT trajectory is feasible, generally safe and may attenuate functional decline, especially when respiratory-focused prehabilitation and supervised multimodal exercise are integrated into care pathways. However, these findings derive from small, mostly single-centre trials with substantial risk of bias and low to very low certainty of evidence; they should therefore be interpreted as hypothesis-generating rather than definitive. Larger, rigorously designed, risk-stratified multicentre trials with standardised functional, respiratory and patient-reported outcomes, as well as hard clinical endpoints, are needed to determine whether optimising pulmonary and physical function can meaningfully improve survival and long-term outcomes in allo-HSCT recipients.