Exercise and Health Counseling in Pediatric Hematopoietic Stem Cell Transplantation

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 \[start of hospitalization for HSCT (i.e., baseline), and 8 weeks and 3 months after hospital discharge, respectively\]: muscle strength (primary outcome), and several fitness/function, clinical burden (i.e., cardiac damage, treatment toxicities, health-related quality of life, among others) and biological variables (omics, blood immune phenotype, microbiome) (secondary outcomes). We will also determine to what extent the benefits of this intervention are maintained over time. Additionally, the investigators will determine the intervention implementability in a real clinical situation in 3 different pediatric HSCT units.

• Change in unilateral knee-extension muscle strength (from baseline to follow-up) [Time frame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)]
• Change in unilateral maximal voluntary isometric contraction of the elbow flexor muscles (at 90º angle) (from baseline to end of treatment) [Time frame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 8-9 weeks post-discharge (i.e., end of treatment)]
• Change in unilateral maximal voluntary isometric contraction of the elbow flexor muscles (at 90º angle) (from baseline to follow-up) [Time frame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)]
• Change in unilateral maximal voluntary isometric contraction of the knee extensor muscles (at 90º angle) (from baseline to end of treatment) [Time frame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 8-9 weeks post-discharge (i.e., end of treatment)]
• Change in unilateral maximal voluntary isometric contraction of the knee extensor muscles (at 90º angle) (from baseline to follow-up) [Time frame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)]
• Change in handgrip strength (from baseline to end of treatment) [Time frame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 8-9 weeks post-discharge (i.e., end of treatment)]
• Change in handgrip strength (from baseline to follow-up) [Time frame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)]
• Change in maximum inspiratory muscle strength (from baseline to end of treatment) [Time frame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 8-9 weeks post-discharge (i.e., end of treatment)]
• Change in maximum inspiratory muscle strength (from baseline to follow-up) [Time frame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)]
• Change in VO2 (mL·kg-1·min-1) at peak (from baseline to end of treatment) [Time frame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 8-9 weeks post-discharge (i.e., end of treatment)]
• Change in VO2 (mL·kg-1·min-1) at peak (from baseline to follow-up) [Time frame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)]
• Change in VO2 (mL·kg-1·min-1) at the ventilatory threshold (from baseline to end of treatment) [Time frame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 8-9 weeks post-discharge (i.e., end of treatment)]