Physical exercise program as an adjuvant therapy for hematopoietic stem cell transplantation: a pilot study

A hematopoietic stem cell transplantation (HSCT) is generally perceived as a
highly strenuous and stressful treatment when viewed from both a physical and
psychological perspective. Regardless this treatment, patients already perceive
feelings of discomfort, insecurity and despair due to the simple fact that they
suffer from a life threatening disease. This existing physical and
psychological burden may be increased substantially while undergoing a HSCT.
The procedure is preceded by intensive chemotherapy and total body irradiation
after which the formation of blood cells needs to restart by use of the
transplanted cells. In the waiting period preceding the HSCT feelings of
insecurity may increase and clinical experience learns that many patients want
to contribute actively to increase their chances of a successful and speedy
recovery.
Over the last years an increasing number of papers describe the promising role
of physical exercise programs as adjuvant therapy for treatments of patients
with cancer. In the specific case of HSCT positive effects have been reported
for tiredness, therapy-related complications (oral and lung infections) and
even a faster recurrence of immune cells (Wiskemann and Huber 2008).
Nevertheless, these findings are still not beyond doubt since many of the
published RCTs suffer from methodological shortcomings and small sample sizes
(n=20). In some cases weaker study designs were used such as before-after
studies without controls (Wiskemann and Huber 2008).
In many of the previous studies (Wiskemann and Huber 2008; Liu et al 2009)
physical exercise programs were given during the clinical phase or even
thereafter whereas we think that physical exercise training might be especially
beneficial in the weeks preceding the HSCT. The disadvantage of only physical
exercising in the period after the HSCT is that the physical condition of many
patients during that period is frail which limits the possibility of delivering
an adequate training stimulus. Furthermore, exercising prior to the HSCT
corresponds well with the desire of many patients to contribute actively to
their treatment in particular during this waiting period. Our proposed exercise
program aims to bring patients in a *top level* physical shape as much as
possible until just before the HSCT in order to decrease the decline and to
speed up recovery afterwards (Wiskemann and Huber 2008).

In preparation of a larger RCT we aim to conduct a pilot study which
investigates the feasibility of the described physical exercise program and its
effects. Purpose of this study is to develop this exercise program, to test the
implementation and conduct of the program within the context of the daily care
at the Department of Hematology of RUNMC and to gain insight into the magnitude
of its effects. This information will be used to calculate the required sample
size of the planned RCT.

A (non-randomized) controlled clinical trial comparing an intervention group
(n=15) which receives the physical exercise program to a control group (n=15)
with usual care. Measurements will be taken at baseline (6 weeks prior to
transplantation), at 6 weeks (just before transplantation) and at 6 weeks and 3
months after transplantation.

The intervention group receives an individually adjusted physical exercise
program of one hour duration which will be administered two times per week
during the 6 weeks prior to the HSCT. The program will be carried out in a gym
which is located at the Department of Physiotherapy at the RUNMC. The program
consists of a warming up, cardiovascular training to improve endurance,
strengthening exercises of large muscle groups, relaxation exercises, breathing
exercises and inspiratory muscle training by use of an inspiratory threshold
loading device (ITLD) (Hulzebos et al, 2006). Both breathing exercises and
inspiratory muscle training are intended to reduce pulmonary complications.
Cardiovascular training will take 15 minutes per session and involves interval
training on stationary bicycles with a work load equivalent to 85-90% of each
participant*s maximum heart rate. Strengthening exercises of large muscle
groups will be carried out on fitness machines (i.e. leg press, chest press,
abdominal crunch, back extension and pull down machine). Three series of
exercises will be carried out of 5 to 8 repetitions at 70-90% of a one
repetition maximum test (1 RM; the maximum amount of weight one can lift in a
single repetition for a given exercise). By using a lighter test load and a
small number of repetitions the 1 RM can be calculated based on existing tables
in textbooks for exercise physiology. To ensure progression, patients will
perform a 1 RM test for each exercise every one and a half week. In addition,
relaxation exercises consist of progressive muscle relaxation. The physical
exercise program will be supervised by a physical therapist who stays in close
contact with a nurse and the treating haematologist by means of a regular
weekly meeting. In the clinical phase after the HSCT patients also receive a
physical exercise program twice a week (as far as possible) during their
hospital stay. This program is already part of current usual care. The control
group receives usual care which means that they have no additional physical
exercise intervention in the 6 weeks prior to the HSCT.

There is a chance that patients may feel uncomfortable or unwell while
exercising. This could take place during the physical exercise program but also
during the measurements (VO2max and Muscle strengths tests). Although physical
exercise programs have often been studied in patients with cancer and also in
HSCT patients we are not aware of any reports in the literature of unwanted
side effects. Further, while exercising patients stay under constant
supervision of a physical therapist and if they feel uncomfortable or unwell
the exercise will be stopped immediately. Contra-indications will be checked by
the Physical Activities Readiness Questionnaire and also after consultation of
the treating haematologist.