Exercise and Stress Management Training For Patients Undergoing Autologous Or Allogeneic Hematopoietic Cell Transplantation. Results From Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0902

Following up on single institution studies suggesting that engaging patients in exercise and/or stress reduction techniques during hematopoietic cell transplantation (HCT) improves functional status and quality of life, we conducted a randomized study through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). METHODS: Patients (n=711) at 21 US centers provided symptom and quality of life data at enrollment. They were randomized to 1 of 4 groups using a 2x2 factorial design, stratified by center and transplant type. Prior to HCT, each group received a 15 minute stress management training session or a 15 minute exercise training session, both, or neither, with trained personnel to discuss the importance of managing stress and/or keeping active during HCT. The 3 intervention groups were also given a DVD, pamphlet and diary to track participation in exercise and/or stress management. The trainer reviewed the goals of practicing the intervention, proper technique, identification of barriers and plans to overcome them. Exercise training also included calculation of target heart rate. The exercise goal was walking 3-5 times a week for at least 20-30 minutes at 50-75% of estimated heart rate reserve. The stress management goal was to use paced abdominal breathing, progressive muscle relaxation with guided imagery, and coping self-statements to decrease stress. The interventionists re-contacted patients at 30 and 60 days after HCT to review the training goals, discuss barriers and provide encouragement. The fourth group was a usual care control group. All groups received a DVD of general information about HCT. Participants provided self-reported assessments at 30, 60, 100 and 180 days after transplant. The primary endpoints were the physical (PCS) and mental (MCS) component subscales of the SF36 at day 100. The study was designed to have 85% power to detect a difference of 0.5 STD in the exercise or stress management groups on each of the two endpoints, maintaining an overall type I error rate of 0.05. Primary analysis was on an intention to treat (ITT) basis with values assigned to patients who died or otherwise did not provide information. Enrollment occurred from January 2011-June 2012.

Results

The groups were well-balanced for baseline characteristics. There were no differences in the primary endpoints of PCS and MCS at day +100 among any of the groups based on the ITT analysis (Table). Results were similar using other conditional and imputed methods. Higher PCS at day +100 was associated with higher PCS at enrollment (p<0.0001), being employed (coefficient 1.85, p=0.01), and having an autologous transplant rather than a myeloablative allogeneic HCT (coefficient 4.47, p<0.0001) or reduced intensity/non-myeloablative allogeneic HCT (coefficient 3.10, p=0.0003). There was no difference between the two types of allogeneic conditioning intensities (p=0.12). Higher MCS at day +100 was associated with higher enrollment MCS (p<0.0001) and higher income (greater than $50,000, coefficient 3.3, p<0.0001). Patients assigned to stress management training reported using these techniques more than those who did not get stress management training. Patients assigned to exercise training did not report greater exercise up to day 100 but this group did report greater activity at day +180 (p=0.04) and better PCS scores at day +180 (coefficient 1.84, p=0.02), although the effect was not significant (p=0.20) in a model including multiple imputation. There were no differences observed in overall survival, hospitalization days until day +100 or in other patient-reported outcomes, including treatment-related distress, sleep quality, pain, and nausea.

Conclusions

No improvements in functional status as measured by PCS and MCS at day +100 were evident between the groups. Functional status was highly associated with pre-transplant functioning and type of transplant but not with conditioning regimen intensity.