Feasibility and Safety of Physical Rehabilitation Interventions in Oncohematologic Patients Following Allogeneic...

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) induces profound physiological disruption across immune, metabolic, and musculoskeletal systems. Despite advances in conditioning regimens and supportive care, no intervention has yet consistently demonstrated the ability to actively restore systemic homeostasis after transplant. Physical rehabilitation has emerged as a biologically plausible intervention with potential multisystem relevance, but its safety and feasibility in the allo-HSCT setting remain uncertain. Establishing these parameters is an essential prerequisite-equivalent to a phase I evaluation-before exploring clinical efficacy. To determine the safety and feasibility of structured physical rehabilitation in adults undergoing allo-HSCT, through a systematic review and meta-analysis of randomized controlled trials (RCTs). This review was conducted according to PRISMA 2020 and prospectively registered in PROSPERO (CRD420251139246). RCTs assessing supervised rehabilitation programs during or after allo-HSCT were included. Risk of bias was evaluated using RoB 2, and certainty of evidence with GRADE methodology. Pooled relative risks were computed using Mantel-Haenszel and DerSimonian-Laird estimators. Thirteen RCTs (≈657 allo-HSCT recipients) were analyzed. Meta-analysis showed no significant differences between rehabilitation and usual care in mortality (RR .98; 95% CI .72 to 1.33) or relapse (RR .94; 95% CI .66 to 1.35), with no signal of increased risk. The pooled rate of adverse events was low and comparable to controls, with most classified as mild (CTCAE grade 1 to 2). Feasibility outcomes showed high adherence (76%) and recruitment (68%) across trials, with no statistical heterogeneity (I² < 25%). Overall evidence quality was low-to-moderate by GRADE. Structured physical rehabilitation after allo-HSCT appears to be safe, feasible, and well tolerated within the contexts studied, particularly at the low- to moderate-intensity ranges represented in randomized trials. This systematic review and meta-analysis consolidates available evidence on safety and feasibility across heterogeneous rehabilitation programs and clinical settings. By providing a robust methodological framework for standardized safety and feasibility reporting, these findings support the responsible design of future multicenter studies aimed at evaluating clinical efficacy and underlying physiological mechanisms.