The role of aerobic physical exercise for adults with haematological malignancies

Review question

We reviewed the existing evidence regarding the effect of aerobic physical exercise plus standard care compared to standard care alone in adults with haematological malignancies. We found nine randomised controlled trials.

Background

A haematological malignancy is a tumour of the myeloid or lymphatic cells. Lymphomas, leukaemias, myelomas, myelodysplastic syndromes and myeloproliferative diseases are all haematological malignancies. These diseases account for nearly 10% of new cancer diagnoses in the United States and are characterised by highly variable and divergent clinical courses and prognoses. Various treatments are available for people with haematological malignancies, from a watch-and-wait approach to single- or multi-agent (combination of drugs) chemotherapy, radiotherapy, immunotherapy and autologous (donor and recipient are one individual) or allogeneic (donor and recipient are two individuals) stem cell transplantation. Additionally, best supportive care is provided to make people more comfortable and to prevent, control or treat complications and side effects. Although people with haematological malignancies have to endure long phases of therapy and immobility which reduces their physical performance level, the advice to rest and avoid intensive exercises is still common practice. This recommendation is partly linked to the reduced number of red cells and platelets from which many patients suffer. The inability to perform activities of daily living restricts them, diminishes their quality of life and may influence medical therapy.

Study characteristics

We searched several databases of medical literature and included nine randomised controlled trials covering 818 people that compared a physical exercise intervention, intending to improve the oxygen system, plus standard care to standard care alone. The majority of people suffered from acute leukaemia, multiple myeloma or lymphoma. In five trials participants received their own stem cells or stem cell transplantation from a donor. The aerobic exercise interventions consisted of various walking programmes of different durations and intensity. The evidence is up-to-date as of January 2014.

Key results

None of the included trials looked at overall survival, although three trials reported how many participants died during the study period or during the first 100 days. There is no evidence for differences in this outcome between the exercise group and the control group.

Four trials measured quality of life (QoL). We dropped one trial from this analysis, due to differences between the groups at baseline. The remaining three trials showed QoL improvements for the exercise arm. Four trials evaluated physical functioning, depression and anxiety, and we combined them in meta-analysis. There is a benefit for the exercise group for physical functioning and depression, but no clear evidence of a difference between exercise and control for anxiety. Seven trials evaluated fatigue, with an advantage for those exercising.

Eight studies assessed the physical performance level (e.g. aerobic capacity, cardiovascular fitness) and in seven of these trials we found a tendency or a statistically significant improvement in the exercise arm.
Three trials measured serious adverse events, and one trial reported adverse events (side effects), but the results of these trials are inconclusive.

Quality of the evidence

The quality of the included evidence is moderate for deaths, physical functioning, and fatigue, low for overall quality of life, depression, anxiety, adverse events and serious adverse events, and very low for physical performance. The main limitations were that participants, physicians and outcome assessors were not blinded, and the low number of participants in the included studies, which meant that we could not exclude the possibility that the intervention had little or no effect.

Authors' conclusions: 

There is no evidence for differences in mortality between the exercise and control groups. Physical exercise added to standard care can improve quality of life, especially physical functioning, depression and fatigue. Currently, there is inconclusive evidence regarding anxiety, physical performance, serious adverse events and adverse events.

We need further trials with more participants and longer follow-up periods to evaluate the effects of exercise intervention for people suffering from haematological malignancies. Furthermore, we need trials with overall survival as the primary outcome to determine whether the suggested benefits will translate into a survival advantage. To enhance comparability of study data, development and implementation of core sets of measuring devices would be helpful.

Read the full abstract...
Background: 

Although people with haematological malignancies have to endure long phases of therapy and immobility which is known to diminish their physical performance level, the advice to rest and avoid intensive exercises is still common practice. This recommendation is partly due to the severe anaemia and thrombocytopenia from which many patients suffer. The inability to perform activities of daily living restricts them, diminishes their quality of life and can influence medical therapy.

Objectives: 

To evaluate the efficacy, safety and feasibility of aerobic physical exercise for adults suffering from haematological malignancies.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2014, Issue 1) and MEDLINE (1950 to January 2014) as well as conference proceedings for randomised controlled trials (RCTs).

Selection criteria: 

We included RCTs comparing an aerobic physical exercise intervention, intending to improve the oxygen system, in addition to standard care with standard care only for adults suffering from haematological malignancies. We also included studies that evaluated aerobic exercise in addition to strength training. We excluded studies that investigated the effect of training programmes that were composed of yoga, tai chi chuan, qigong or similar types of exercise. We also excluded studies exploring the influence of strength training without additive aerobic exercise. Additionally, we excluded studies assessing outcomes without any clinical impact.

Data collection and analysis: 

Two review authors independently screened search results, extracted data and assessed the quality of trials. We used risk ratios (RRs) for adverse events and 100-day survival, standardised mean differences for quality of life (QoL), fatigue, and physical performance, and mean differences for anthropometric measurements.

Main results: 

Our search strategies identified 1518 potentially relevant references. Of these, we included nine RCTs involving 818 participants. The potential risk of bias in these trials is unclear, due to poor reporting.

The majority of participants suffered from acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), malignant lymphoma and multiple myeloma, and six trials randomised people receiving stem cell transplantation. Mostly, the exercise intervention consisted of various walking intervention programmes with different duration and intensity levels.

Our primary endpoint of overall survival (OS) was not analysed in any of the included trials, but three trials reported deceased participants during the course of the study or during the first 100 days. There is no evidence for a difference between participants exercising and those in the control group (RR 0.93; 95% CI 0.59 to 1.47; P = 0.75; 3 trials, 269 participants, moderate quality of evidence).

Four trials analysed the influence of exercise intervention on quality of life (QoL). Excluding one trial with serious baseline imbalances, physical exercise improves QoL (SMD 0.26; 95% CI 0.03 to 0.49; P = 0.03; 3 trials, 291 participants, low quality of evidence). This positive effect of exercise was also found in the subscales physical functioning (SMD 0.33; 95% CI 0.13 to 0.52; P = 0.0009; 4 trials, 422 participants, moderate quality of evidence) and depression (SMD 0.25; 95% CI -0.00 to 0.50; P = 0.05; 3 trials, 249 participants, low quality of evidence). However, there is no evidence for a difference between additional exercise and standard treatment for the subscale anxiety (SMD -0.18; 95% CI -0.64 to 0.28; P = 0.45; 3 trials, 249 participants, low quality of evidence). Seven trials (692 participants) evaluated fatigue. There is moderate quality of evidence that exercise improves fatigue (SMD 0.24; 95% CI 0.08 to 0.40; P = 0.003).

Eight studies evaluated various aspects of physical performance (e.g. aerobic capacity, cardiovascular fitness), but none of them could be pooled in a meta-analysis. In seven trials there is a tendency or statistically significant effect favouring the exercise group (very low quality of evidence).

Three trials (266 participants) investigated serious adverse events (SAEs) (e.g. bleeding, fever, pneumonia, deep vein thrombosis, and infection), and one trial (122 participants) assessed adverse events (AEs). There is no evidence for a difference between arms in terms of SAEs (RR 1.44; 95% CI 0.96 to 2.18; P = 0.06) or AEs (RR 7.23; 95% CI 0.38 to 137.05; P = 0.19); both findings are based on low quality of evidence.

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