Physical Activity in Children During Hematopoietic Stem Cells Transplantation (HSCT)
Condition: Hematopoietic Stem Cell Transplantation; Child; Adolescent
Study type: Interventional

Summary: 
      This interventional study was designed to assess the validity and the impact of a
      rehabilitation program on pediatric cancer patients undergoing hematopoietic stem cells
      transplantation (HSCT). Each participant will be randomly assigned to either an experimental
      or control (counseling rehabilitation care) group. The experimental group participate in an
      inpatient rehabilitation program for the duration of HSCT pathway. The program include
      standardized activities for 5 days a week in the child's room or in a pediatric gym at the
      hospital.
    

Detailed description: 
      BACKGROUND Hematopoietic stem cell transplantation (HSCT) is a potentially curative option
      for many diseases, such as hematologic malignancies and refractory solid tumors among
      children and adolescents. This procedure led to considerable improvement in survival rates,
      but also contributed to the development of late effects. Due to the severity of conditioning
      regimen, length of isolation and hospitalization period, weakness related to
      immunosuppression and drug toxicities, physical, cognitive and psychosocial functions are
      severely impaired. HSCT recipients may report impairments in cardiorespiratory fitness
      (fatigue), muscle bulk and strength, immunologic recovery, neuropsychological functions,
      functional abilities and autonomy with an undeniable decline of quality of life (QoL).
      Recently pediatric oncological research attentions have been directed to reduction of the
      impact of these side effects and to improvement of QoL, both during and after cancer
      treatment. The published studies about the effects of rehabilitation care, in pediatric
      population undergoing HSCT show how rehabilitation, which consists in structured and adapted
      different therapeutic activities, is safe and feasible. In particular studies conducted on
      the inpatient phase for HSCT report how the execution of a low intensity level of activity
      doesn't have any bad effect on immunological recovery, positively affects BMI, gives benefits
      on general health status, improves QoL, protects from depressive symptoms by promoting a
      healthy lifestyle during survivorship. Moderate exercise in a chronic graft-versus-host
      disease (cGVHD) murine model receiving total body irradiation (TBI) and immunosuppression can
      reduce clinical severity scores, blood interleukine-4 (IL-4) and tumor necrosis factor α
      levels while increasing survival, physical fitness, circulating B220 and cluster of
      differentiation 4 (CD4) lymphocytes. Finally, rehabilitation can improve immune function
      which has an impact on cancer control. Pediatric Oncohaematology Department of "Regina
      Margherita" Children's Hospital in Turin ["A.O.U. Città della Salute e della Scienza"] is one
      of the most important structure in Italy for pediatric HSCT. In the year 2016, 47 patients
      underwent HSCT: 25 of them were less than 11 years old and 22 were older than 11 years. In
      2017, until the month of August, 25 patients were transplanted: 12 of them were less than 11
      years old and 13 were older than 11 years. The in-patient phase lasted for a medium time of
      40 days. From a recent review of the Department, in the period between March 2010 and
      November 2015, 207 children and adolescent patients benefited of a rehabilitation treatment,
      42 of these during and after hospitalization for HSCT. However, to date rehabilitation
      programs have been implemented in a purely personalized perspective thus ignoring primary
      methodological issues (e.g., absence of a control group) which would allow an appropriate
      evaluation of outcomes generalizable to the target population. Therefore, rigorous
      interventions are mandatory in order to prevent future long-term treatment effects, to
      improve general health state of these patients and to share evidence-based guidelines for the
      optimal design for rehabilitation care in pediatric oncology.

      EXPERIMENTAL PROJECT Starting from literature data on benefits of participation to a
      rehabilitation program for subjects undergoing HSCT, the current research intends to propose
      a project in a prevention perspective aim at the promotion of healthy life style for children
      and adolescents.

      Procedures According to the difficulties reported in other studies that had both exercise
      group (EG) and control group (CG) patients recovery at the same time, and since this led to
      inevitable contamination between these two groups, investigators established that eligible
      patients who provided consent will be assigned to one of the two groups according to a
      "cluster time" selection model. The study it has been approved by the hospital's Ethical
      Committee. Written informed consent will be obtain from the participants or from their
      parents/guardians for patients under eighteen.

      Exercise Intervention The study is presented to eligible patients and to their caregivers by
      a Development Neuro and Psychomotor Therapist in an interview. The interview regards: 1)
      problems that may occur during the HSCT procedure; 2) the importance of rehabilitation during
      the recovery to limit side effects; 3) presentation of the study design and procedures; 4)
      submission of the informed consensus. After having obtained the consensus, patients are
      assigned to the EG or the CG, according to the methodology previously explained. Subjects
      receive information booklets containing practical rehabilitation instructions, expressed in
      both text and illustrations, differentiated by the three identified age ranges (0-4, 5-12,
      13-18). The content of booklets varies between EG and CG, since in the first case it contains
      both exercise and RCI, while for CG it regards only on RCI.

      EXPERIMENTAL GROUP: The intervention consists in a standardized PE and RCI. PE is done 5
      days/week (2 days in autonomy by the patient with parents support and 3 days supervised).
      Each session lasts 30 minutes and this is supervised by one therapist for all patients.
      Children aged less than 5 years make activities directed to sustain and promote their
      neuro-psychomotor development and muscle strength (e.g. to sit in the infant seat, playing in
      sitting position without support, playing on the floor and to crawl). Patients belonging to
      the other two age ranges are enrolled in an exercise programme (EP) composed by three
      different types of exercises, each carried out for 10 minutes per session: muscle strength
      exercises for upper and lower extremities preceded by warming up, aerobic exercises and
      stretching. For children aged 5-12 years activities are based principally on games (e.g.
      games with the ball, with circles and bricks, etc.), while structured exercises are proposed
      to adolescents (e.g. using weights, treadmills or exercise bikes); in both groups, the active
      videogames of Nintendo Wii(™) Fit is used to promote aerobic training. The EP is done only if
      the patient had platelets > 20000 and Hb > 8.0. Patients belonging to the upper age ranges
      also benefit from RCI, which has to be followed daily, and where some practical advice are
      given on how to adopt an active lifestyle during the recovery (e.g., getting up to go to the
      bathroom, getting up to move to the window to talk with visitors, sit on chair to have school
      lessons).

      Parents record daily their child's EP and RCI activities in appropriate grids, and
      adolescents filled them in themselves.

      CONTROL GROUP: Parents of children who belonged to the 0-4 years old age range CG receive a
      booklet with some RCI on how to reduce the time spent in bed and to propose different kinds
      of activities useful to sustain their development, according to the functional level of their
      child. Children who aged more than 5 years and adolescents of the CG receive the same part of
      the pamphlets given to the EG, containing written and illustrated indications of the RCI. The
      RCI has to be followed daily. Parents are required to record in appropriate grids their
      child's daily activities and adolescents filled them in themselves. The therapist goes 3
      times/week to check that the diary has been filled in correctly.

      EXPECTED RESULTS (experimental group vs control group): - Stable level of gross motor skills,
      functional motility, resistance to the walking and muscular strength from T0 and T1; - Stable
      level in passive articular movement in tibial artery dorsiflexion from T0 and T1; - Stable
      level of muscular elasticity from T0 and T1; - High perception of QoL and less fatigue from
      T0 and T1; - Improvement in immune functions; - Positive association between food intake and
      program participation.

      FUTURE APPLICATIONS TO HEALTH The current project seeks to obtain not only important health
      and clinical benefits for patients undergoing HSCT in terms of late diseases reducing (e.g.,
      obesity), but it will also underline new important association between exercise and
      biological system useful to find new insight for antitumor mechanisms. Also the need to
      improve several rehabilitation issues will be showed. For instance, the project will allow to
      focus on the importance that all patients have access to rehabilitation options. Actually,
      there is currently a gap between what investigators know from research, and what health care
      professionals, are implementing in pediatric cancer care. In Italy, for instance, the
      possibility to benefit of rehabilitation care is still poor because of the absence of
      services and facilities in several centres of pediatric oncology. So, to pay attention to
      these unmet needs will be the first step towards the reduction of the financial burden of
      hospitalization because of late effects problems and secondary disease some of which can be
      prevented with an appropriate rehabilitation program.
    

Intervention name(s): exercise and rehabilitation counselling; rehabilitation counselling
Intervention type(s): Other; Behavioral
Intervention description(s): The intervention consists in a standardized physical exercise (PE) and rehabilitation counselling indications (RCI). PE is done 5 days/week (2 days in autonomy by the patient with parents support and 3 days supervised). Each session lasts 30 minutes and this is supervised by one therapist for all patients. Patients are enrolled in an EP composed by three different types of exercises, each carried out for 10 minutes per session: muscle strength exercises for upper and lower extremities preceded by warming up, aerobic exercises and stretching. The kind of exercise is differentiated by age range (children, 5-12 years and adolescents, 13-18 years).; RCI, which have to be followed daily, consist in some practical advice was given on how to adopt an active lifestyle during the recovery (e.g., getting up to go to the bathroom, getting up to move to the window to talk with visitors, sit on chair to have school lessons).
Other intervention name(s): rehabilitation
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Intervention model description: Eligible patients who provided consent were assigned to one of the two groups according to a "cluster time" selection model. The methodology was discussed and agreed with expert methodologists of the A.O.U. Città della Salute e della Scienza research group and based assignation to the two groups according to the time of hospitalization: EG enrollment May 2016-December 2016, March 2017-May 2017, November 2017-June 2018 and CG enrollment January 2017-February 2017, June 2017-October 2017, July 2018-August 2018.
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Physiotherapy; Rehabilitation; Exercise