A-CaRe study 3: Exercise intervention after stem cell transplantation.

Background:

Physical exercise interventions after stem cell transplantation can have positive effects on physical fitness, fatigue and quality of life in hematologic patients who have undergone high dose chemotherapy and autologous stem cell transplantations. However, the trials conducted so far were of poor to moderate quality. Also data on cost-effectiveness of these interventions are not available. Hence there is a need for a rigorous, appropriately controlled assessment of the (cost-)effectiveness of exercise programs in these patients.



Purpose:

The study is part of a larger research program (A-CaRe) which is sponsored by the Alpe D'HuZes foundations and coordinated by the EMGO institute in Amsterdam. The objectives of the current study are: (1) to determine the effectiveness of a state-of-the-art individualized high intensity strength and interval training program with respect to physiological and psychological status in patients with multiple myeloma and (non-)Hodgkin’s lymphoma who have recently undergone HDC followed by ASCT and (2) to evaluate the cost-effectiveness of this exercise program.



Plan of investigation:

Following a small pilot study to evaluate feasibility of the process of training and assessments according to a detailed manual, a prospective, randomized controlled trial will be performed in 120 patients with multiple myeloma or relapse (non-)Hodgkin’s lymphoma who have undergone induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation. Patients will be randomized to either the intervention group or the control group.

The intervention will start 6-12 weeks after SCT and will consist of an 18 weeks supervised high intensity exercise program (2x/wk for the first 12 weeks and 1x/wk for the last 6 weeks; aerobic and resistance exercise). 3 booster sessions at increasing (4, 10, 18 weeks after completion of the intervention program) will be held during which patients are trained and counselled and motivated to continue exercising and maintain active lifestyle in general. The control group will receive standard care. Patients will be followed until 12 months after the end of the intervention program or a comparable time after SCT in the control group.

The primary outcome variables are fatigue, cardiorespiratory fitness and muscle strength. Secondary outcome measures include adherence and compliance, health-related quality of life, physical activity, mood disturbance and return to work. A cost-effectiveness analysis will be performed.



Relevance:

If demonstrated to be effective, the availability of the intervention will be a welcome addition to the standard care of patients with of haematological cancer patients treated with high dose chemotherapy and autologous stem cell transplantation.

Stem cell transplantation survivors who received the high-intensity strength and interval training program will (1) have an improved physical fitness, (2) report lower levels of fatigue, (3) report less mood disturbances, higher levels of daily activities and an improved health-related quality of life, (4) have a higher partial and full return to work rate compared to stem cell transplantation survivors who received standard care only.

In addition, the high intensity strength and interval exercise program is more cost-effective compared to current standard care.

1. T=0: Baseline, 6-12 weeks after SCT and prior to randomisation;

2. T=1: At completion of the 18-week intervention;

3. T=2: 12 weeks months after ending the intervention.

Besides the standard care patients in the intervention arm follow an 18-weeks exercise. This program consists of high-intensity resistance and interval training. Before the start of the program, a sport physician will screen the patient and, where necessary adapt the program. Training takes place twice a week (first 12 weeks) and later once a week in physical therapy practices supervised by physical therapists. Patients will train on specialized resistance training equipment and on bicycle ergometers. Furthermore, the physical therapist will coach the patient to maintain an active lifestyle from week 10 onwards.
Resistance exercise consist of six exercises targeting the large muscle groups: (1) vertical row; (2) leg press; (3) bench press; (4) pull over; (5) abdominal crunch; (6) lunge. Indirect one repetition maximum (1-RM) measurements will be performed every 4 weeks for all six exercises. In the first 12 weeks, the resistance exercise consists of two sets of 10 repetitions at 65 to 80% of the 1-RM. From week 12 onwards it comprises of more repetitions (20 repetitions per set) at a lower resistance (35-40%).
Before and after the resistance exercise patients cycle two times eight minutes with alternating resistance. To determine right resistance a steep ramp test will be performed every 4 weeks. With this test the subject is instructed to cycle at a speed between 70 and 80 rpm, starting at a work rate f 25 Watt for 30 seconds. Hereafter the load is increased by 25 watt every 10 seconds till exhaustion. Maximal short exercise (the maximal workload, MSEC) is recorded. In the first 8 weeks, blocks of 30 seconds at 60% will be alternated with blocks of 60 seconds at 30%. From week nine onwards, the duration of the latter block is reduced to 30 seconds.
The counselling is based on the Onco-Move program ('Every Step Counts). Patients will be encouraged to achieve and maintain a physically active lifestyle including moderate to vigorous activities for a period of at least 30 minutes 4 to 6 days per week. An information folder wherein information about physical activity and desired intensity based on the Borg Scale of perceived exertion will be given to the patient. During the counselling sessions, the physical therapist will verbally explain the information. Besides for providing information, the sessions will be used for filling out the activity diary of the previous weeks, evaluate experienced difficulties with being active and formulate objectives for the coming period.



Both the patients in the intervention arm and the patients in the control arm receive standard care. However, since currently the usual care is not standardized, the care will vary according to doctors’ and patients’ preferences. Patients in the control arm are allowed to participate in sports.