During the intervention phase (hospitalization for hematopoietic stem cell transplantation (HSCT) and subsequent 8-week outpatient phase following discharge), the control group will participate in a Health Counseling Program (1 time/week) on aspects related to a healthy lifestyle such as reducing sedentary lifestyle, acquiring healthy nutritional habits, the importance sleep, screen use, and how to address barriers related to clinical status. We will adapt the program to the needs and timing of the patient's treatment, providing the content in one session/week orally (e.g. using presentations) and in writing (e.g. through brochures).

During the intervention phase (hospitalization for hematopoietic stem cell transplantation (HSCT) and subsequent 8-week outpatient phase following discharge), the intervention group will participate in exactly the same Health Counseling Program as the Control group. Additionally, this group will perform an exercise program combining aerobic and muscle strength exercises

During the intervention phase (hospitalization for HSCT and subsequent 8-week outpatient phase following discharge), the control group will participate in a Health Counseling Program (1 time/week) on aspects related to a healthy lifestyle such as reducing sedentary lifestyle, acquiring healthy nutritional habits, the importance sleep, screen use, and how to address barriers related to clinical status. We will adapt the program to the needs and timing of the patient's treatment, providing the content in one session/week orally (e.g. using presentations) and in writing (e.g. through brochures).

Control Group (Active Comparator)

Same as Control Group + exercise program as described below:

Same as Control Group + exercise program as described below:

Hospital ward (during HSCT); and Hospital Gym or online (patients' home) during the outpatient phase. Frequency: 3-5 days/week. Session duration: 30 to 55-60 minutes Aerobic training (5-25 minutes): bicycling, crank-ergometry, circuit-style exercises, and games. Muscle strength training (10-20 minutes): large muscle group exercises (upper/lower limb + trunk exercises) performed as a circuit using body weight or against resistance (against gravity and with body weight, elastic bands, dumbbells, weighted vests, machines), with a wide range of joint mobility and at submaximal/maximum voluntary speed. Inspiratory muscle training will also be performed (5 min daily, using a specific device that creates resistance against inspiration).

Intervention Group

Carmen Fiuza-Luces, PhD

Thanks to medical advances, survival rates \>5 years in children/adolescents undergoing hematopoietic stem cell transplant (HSCT) exceed 70%. However, these patients are at high risk of suffering sequelae associated with the underlying disease and/or the HSCT itself, which negatively affects their physical capacity. These patients also tend to spend too much time inactive, which further accelerates functional decline in addition to producing fatigue and impairing quality of life. Therefore, new strategies are needed to minimize the morbidity associated with HSCT. In this effect, although physical exercise represents an interesting adjuvant treatment option for HSCT, scientific evidence in this area is still scarce. Implementation of physical exercise intervention in pediatric HSCT units is challenging due to the lack of research on the effectiveness, affordability and accessibility of this type of intervention. Therefore, establishing the effectiveness of physical exercise under controlled conditions is an important step. The investigators therefore aim to assess the impact of a physical exercise and health counseling program, compared to health counseling only (control group), in pediatric patients with cancer undergoing HSCT on physical-functional, behavioral, psycho-cognitive and clinical outcomes, and blood biomarkers. The investigators will also determine to what extent the benefits of this intervention are maintained over time. Additionally, the investigators will determine the feasibility of implementing the proposed intervention in a real clinical situation in 3 different pediatric HSCT units.

Hematopoietic stem cell transplantation (HSCT), which is used to treat high-risk malignancies, as well as some other conditions or even autoimmune processes, consists of several phases: mobilization and subsequent collection of hematopoietic stem cells from the patient (autologous HSCT) or from a donor (allogeneic HSCT); pre-HSCT conditioning; infusion of patient/donor cells; establishment of a new immune and hematopoietic system in the recipient; and prophylaxis/treatment of possible adverse effects. Since the first successful allogeneic transplant was performed in 1968, thanks to the advances experienced in conditioning regimens, as well as in donor-recipient histocompatibility testing, in patient care and in the management of graft versus host disease (GvHD), together with the increase in the number of donors, the expectations of children and adolescents who receive HSCT have improved, achieving long-term survival rates (\>5 years) \>70%. Yet survivors are at high risk of suffering side effects and toxicities derived from the HSCT itself and/or the underlying disease, with subsequent functional decline. In addition, they show a higher risk of rehospitalization than pediatric cancer survivors who did not receive HSCT and tend to develop chronic pathologies (especially cardiometabolic conditions and frailty) at earlier stages of adulthood than the general population.

The investigators therefore aim to assess the impact of a physical exercise and health counseling program, compared to health counseling only (control group), in pediatric patients with cancer undergoing HSCT on the following outcomes assessed at 3 time points \[start of hospitalization for HSCT (i.e., baseline), and 8 weeks and 3 months after hospital discharge, respectively\]: cardiorespiratory fitness (primary outcome) and ventilatory threshold, muscle strength, left ventricle ejection fraction, fractional shortening and global longitudinal strain, total cardiac mass, functional mobility, adiposity (waist to hip ratio), body mass index, dual-energy X-ray absorptiometry (DXA)-determined body composition (lean and fat mass, bone mineral density), accelerometry-determined physical activity levels, ankle dorsiflexion range of motion, health-related quality of life, cancer-related fatigue, and immune subpopulations. We will also determine clinical outcomes during hospitalization (survival, treatment tolerability, toxicities) as well as molecular biomarkers in blood.

The staff in charge of outcome assessment will be blinded to the group assigned to each participant.

Exercise and Health Counseling in Pediatric Hematopoietic Stem Cell Transplantation

Physical Exercise and Health Counseling in Patients With Pediatric Cancer Patients Undergoing Hematopoietic Stem Cell Transplantation: From Research to Clinical Reality.

CRF assessed as peak oxygen uptake, as determined during a ramp bicycle ergometer test until volitional exhaustion (unit = mL of oxygen/kg body mass/minute),

CRF estimated with 6-minute walking distance (maximum distance achieved) (unit = meters)

Dynamometer-determined maximal isometric strength of knee flexor muscles (unit = Newtons)

One-repetition maximum (1RM) during leg press exercise, as estimated from 5RM leg press (unit = kg)

Maximal handgrip strength, mean of 3 attempts with both arms (unit = kg)

Maximal inspiratory pressure (unit = mm H20)

Workload eliciting the ventilatory threshold, as determined during the ramp test (unit = watts)

Echocardiography-determined LV ejection fraction (unit = percent)

Echocardiography-determined LV fractional shortening (unit = percent)

Echocardiography-determined GLS of the LV (unit = percent)

Echocardiography-determined total cardiac mass (unit = grams divided by body surface area (im meters squared)

Stairs test (time to walk up and down a 12-step stair) (unit = seconds)

Sit-stand test (time to stand from a chair 5 times) (unit = seconds)

We will use the Quick Motor Function test, which takes approximately 10 to 15 minutes. An evaluator observes the performance of a patient and scores the 16 items separately on a 5-point ordinal scale (ranging from 0 to 4). If items can be performed on both left and right extremities, the right side is taken. A total score is obtained by adding the scores of all items. The total score ranges between 0 and 64 points (units = points, from 0 to 64)

BMI is measured as weight (kg) divided by height squared (m2)

DXA-determined bone mineral density (unit = grams/m2)

PA levels (moderate/vigorous PA) determined using triaxial accelerometry (unit = minutes/week)

Goniometer-determined active and passive ankle range of motion in dorsiflexion (unit = degrees)

Health-related QoL (HRQoL) (Paediatric Quality of Life Inventory \[abbreviated as PedsQL 4.0\] Cancer Module \[3.0\], designed to measure paediatric/adolescent cancer specific HRQoL) (unit = 0 to 100 scale, with higher scores indicating better HRQoL)

Cancer-related fatigue (Paediatric Quality of Life (PedsQL 3.0) Multidimensional Fatigue Scale) (0 to 100 score, higher scores meaning higher fatigue)

Flow-cytometry determined lymphocyte subpopulations (unit = %)

Flow-cytometry determined natural killer (NK) cell subsets (unit = %)

Survival (number of days from diagnosis to the end of the study or death)

Treatment interruption/delay (number of days)

Common Toxicity Criteria for Adverse Events \[CTCAE, global score, 1 (low toxicity) to 5 (highest\])

Panel of cytokines/chemokines and peptides (oncostatin-M, osteonectin, FGF21, irisin, follistatin-1, musclin, VEGF-A, fractalkine, interleukin (IL)-8, IL-6 and IL-15 in serum using Luminex® (all assessed in the same units, micrograms/dL) before and after a single exercise training session

RNA sequencing (RNAseq) profile in peripheral blood mononuclear cells under resting conditions at baseline and 8 weeks after hospital discharge

RNA sequencing (RNAseq) profile in peripheral blood mononuclear cells before and after a single exercise training session

RNA sequencing (RNAseq) profile in peripheral blood mononuclear cells before and after and exercise training session

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Exercise and Health Counseling in Pediatric Hematopoietic Stem Cell Transplantation	NCT06300515	Hematopoietic S...	Control Group (... Intervention Gr...	4 Years - 21 Years	Universidad Europea de Madrid
Exercise and Health Counseling in Pediatric Hematopoietic Stem Cell Transplantation	NCT06300515	Hematopoietic S...	Control Group (... Intervention Gr...	4 Years - 21 Years	Universidad Europea de Madrid

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