Prehabilitation to Improve Frailty, Function, and Quality of Life in Candidates for Hematopoietic Stem Cell Transplantation

Effects of a Prehabilitation Program on Frailty, Function, Quality of Life, and Post-Transplant Outcomes in Candidates for Hematopoietic Stem Cell Transplantation: A Randomized Clinical Trial

Candidates for hematopoietic stem cell transplantation (HSCT) frequently experience declines in strength, physical function, and quality of life before the procedure. Many also present fatigue, limitations in daily activities, and an increased risk of complications during and after hospitalization. Optimizing physical condition before transplantation may improve post-procedure recovery.

This study will evaluate whether a prehabilitation program improves physical function, frailty, and quality of life in adults preparing for HSCT. The intervention consists of supervised exercise, education, and activities designed to enhance endurance and functional capacity. Although prehabilitation has shown benefits in other oncologic populations, it has been minimally studied in HSCT candidates, and no structured programs have been evaluated in Chile.

A total of 68 adults will be randomly assigned to a prehabilitation group or a usual-care control group. The prehabilitation group will receive a personalized program including aerobic and resistance exercise, stretching, balance training, respiratory exercises, and education on healthy behaviors, delivered through a hybrid model of in-person and remote sessions. Occupational therapy will also be provided to support functional and cognitive abilities. The control group will continue with standard medical care.

Baseline and post-intervention assessments will include measures of strength, frailty, fatigue, balance, cognitive function, daily activities, and quality of life. Post-transplant outcomes such as hospital length of stay, complications, and readmissions within three months will also be recorded. Feasibility, adherence, satisfaction, and adverse events will be evaluated.

Findings from this trial may inform the development of structured prehabilitation programs for HSCT candidates and support the implementation of evidence-based supportive care strategies in hematologic oncology.

Hematopoietic stem cell transplantation (HSCT) is a complex treatment widely used for hematologic malignancies. Although it offers curative potential, many patients experience significant declines in physical functioning, increased frailty, fatigue, and reduced quality of life before and after transplantation. Lower functional reserve prior to HSCT has been associated with greater treatment-related complications, longer hospital stays, and slower recovery. Despite growing evidence supporting exercise-based interventions in cancer care, prehabilitation has been minimally studied in HSCT candidates, and no structured prehabilitation program has been tested in Chile.

This randomized clinical trial investigates whether a multimodal prehabilitation program delivered before HSCT can improve frailty, functional capacity, quality of life, and early post-transplant outcomes. The intervention combines supervised aerobic and resistance exercise, balance and flexibility training, respiratory exercises, education on healthy behaviors, and a structured home-based component. A hybrid delivery model (in-person and remote sessions) allows tailoring to individual needs and supports continuity of care. Occupational therapy sessions complement the program by addressing cognitive and functional abilities relevant to daily activities.

A total of 68 adults preparing for HSCT will be randomized in a 1:1 ratio to either the prehabilitation group or a usual-care control group. The study uses concealed allocation and blinded outcome assessment. Feasibility-including adherence, acceptability, and reported adverse events-will also be evaluated to determine whether the program can be safely and efficiently implemented in a real-world transplant setting.

The results of this trial will provide new evidence on whether prehabilitation can strengthen physical resilience before HSCT, reduce early post-transplant complications, and support better recovery. Findings may guide the development of standardized prehabilitation programs for patients undergoing HSCT and inform national recommendations for supportive care in hematologic oncology.

Inclusion Criteria:

• Adults aged ≥18 years
• Diagnosis of hematologic malignancy requiring HSCT (autologous or allogeneic).
• Minimum of ≥4 weeks available before the scheduled transplant.
• "Pre-frail" or "frail" according to the HCT Frailty Scale.
• ECOG ≤2 or Karnofsky ≥60.
• Internet access (videocalls, Zoom platform, or a facilitator) for remote sessions.

Exclusion Criteria:

• Cognitive impairment preventing questionnaire completion.
• Musculoskeletal comorbidities preventing participation in supervised exercise-based prehabilitation.
• Prior chemotherapy or radiotherapy not related to the hematologic malignancy.
• Medical conditions limiting participation (e.g., unstable angina, arrhythmia, hypertension or heart failure, acute systemic infection with fever, acute myocarditis, or pericarditis).