Effects of exercise in patients treated with stem cell transplantation for a hematologic malignancy: A systematic review and meta-analysis

Abstract

We performed a systematic review and meta-analysis evaluating the effectiveness of exercise interventions compared with usual care on physical fitness, fatigue and health-related quality of life in patients with hematologic malignancies treated with stem cell transplantation. Electronic databases were searched up to June 2012. We included randomized controlled trials comparing exercise with usual care, in which at least 75% of the patients had a hematologic malignancy. Standard mean differences were calculated and pooled to generate summary effect sizes (ES) and 95% confidence intervals (CI). The Cochrane Collaboration Risk of Bias Tool was used to assess the methodological quality of the studies.

Eight studies met our inclusion criteria. Exercise had a statistically significant moderately favourable effect on cardiorespiratory fitness (ES = 0.53, 95% CI = 0.13–0.94), lower extremity muscle strength (ES = 0.56, 95% CI = 0.18–0.94) and fatigue (ES = 0.53, 95% CI = 0.27–0.79). Significant small positive effects were found for upper extremity muscle strength, global quality of life, and physical, emotional and cognitive functioning. In conclusion, exercise seems to have beneficial effects in patients treated with stem cell transplantation. However, all studies had at least some risk of bias, and for cardiorespiratory fitness and lower extremity muscle strength substantial heterogeneity in effect sizes were observed. Further high quality research is needed to determine the optimal exercise intervention and clinical implications.

Introduction

Autologous stem cell transplantation (Auto-SCT) is standard of care for patients with multiple myeloma in first line, and for patients with Hodgkin lymphoma and aggressive non-Hodgkin’s lymphoma at first relapse. The transplant-related mortality is below 5%. Allogeneic stem cell transplantation (Allo-SCT) can improve outcome in patients with standard or high risk acute myeloid leukaemia or acute lymphoblastic leukaemia. However, in 15–20% of cases complications such as graft-versus-host disease and infections lead to transplant-related mortality. Currently, the five year event-free survival for the hematologic malignancies most often treated with stem cell transplantation (SCT) ranges from 5–80%.¹ With 50,000 SCTs performed annually worldwide,2, 3 the number of SCT survivors increases rapidly.

Despite advances in supportive care, SCT is still associated with serious morbidity. In addition to graft-versus-host disease and infections, short term complications include nausea, diarrhea, mucositis, pain, anxiety and depression.⁴ Although most survivors recover adequately from treatment, a substantial proportion continues to experience psychosocial and/or physical long-term and late effects that reduce health-related quality of life (HRQoL).⁵ One of the most prevalent and disturbing long term problems is fatigue.6, 7, 8, 9

It is hypothesized that persistent fatigue reflects a self-perpetuating condition: cancer, its treatment and the associated bed rest lead to poor physical fitness. As a result, greater effort is required to fulfil the activities of daily living, and performance of these activities can induce abnormally high levels of fatigue. In order to minimize fatigue, patients will limit their physical activities, which will eventually lead to an even greater decline in physical fitness. An exercise intervention might reverse this downward sequence.10, 11, 12, 13, 14 Currently, the American College of Sports Medicine states that for certain cancer survivor groups, exercise training is safe and results in improved physical functioning and HRQoL, and reduced fatigue.¹⁵ However, the effectiveness of exercise interventions in patients during or after SCT has not yet been fully established. Liu et al.¹⁶ and Wiskemann et al.¹⁷ concluded in their systematic reviews that exercise has positive effects on physical fitness, HRQoL and psychological well-being, but that this evidence is based on studies of low methodological quality. In a more recent review, Wolin et al.¹⁸ concluded that physical activity for adult SCT patients has numerous potential benefits, but they only found weak evidence (defined as ⩾3 high-quality studies, but <75% reporting a significant benefit) for a beneficial effect of exercise on physical fitness, fatigue, and HRQoL.

The field of cancer rehabilitation expands rapidly. More studies with larger sample sizes on the effectiveness of exercise during or after SCT have been published since Wolin et al.,¹⁸ which warrants a new systematic review of the present evidence. Furthermore, the increasing number of published studies allows us to apply stricter in- and exclusion criteria concerning study design and study populations in order to reduce heterogeneity. Hence, the objective of the current review is to systematically review the evidence on effectiveness of exercise interventions in comparison to usual care with respect to physical fitness, fatigue and HRQoL in patients treated with SCT for a hematologic malignancy.