What is the aim of this review?
The aim of this Cochrane Review was to find out whether aerobic physical exercise can improve health, or play a supporting role for adult patients suffering from haematological malignancies. We collected and analysed all relevant studies to answer this question and found 18 relevant studies, of whom 14 reported our pre-defined patient-relevant outcomes.
Aerobic physical exercise probably has a positive effect on fatigue and depression of patients with haematological malignancies. Evidence related to mortality, quality of life, and serious adverse events is still unclear.
What was studied in the review?
Haematological malignancies are tumours of the blood-forming system, such as lymphomas, leukaemias, myelomas, myelodysplastic syndromes and myeloproliferative diseases. These diseases represent approximately seven per cent of new cancer diagnoses worldwide. Treatment strategies include wait-and-watch approaches, chemotherapy, radiotherapy, immunotherapy and stem cell transplantation, as well as supportive care to prevent, control or treat complications and side effects.
Although these patients have to endure long phases of therapy and immobility, which has a negative effect on their physical performance level, it is still common practice to recommend rest and to avoid intensive exercise.
There are several studies and approaches that try to establish another strategy and to include physical exercise, especially aerobic physical exercise, into the treatment strategy of haematological malignancies. In detail, these exercise programmes consist of aerobic, resistance and flexibility components, partly home-based. Some prefer it to be integrated in daily living. A common method is also the use of tools such as bicycle ergometers or stretch bands as well as walking exercises. Aerobic physical exercise might improve oxygen supply to muscles and tissues of the body.
What are the main results of the review?
The review authors of this review update identified nine new trials which could be added to the nine trials of the first version of this review. Of these 18 trials, 14 trials provided sufficient data to be meta-analysed. Although six 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.
Eight trials measured quality of life, physical functioning and anxiety and did not show any evidence for a difference between additional exercise and usual care. There might be a benefit for the exercise group in terms of fatigue and depression.
The evidence for serious adverse events is based on very low certainty, therefore results are still uncertain.
In addition, we are aware of four ongoing trials. However, none of these trials stated, how many patients they will recruit and when the studies will be terminated, thus, potential influence of these trials for the current analyses remains unclear.
How up-to-date is the review?
The review authors searched for studies that had been published up to July 2018.
Eighteen, mostly small RCTs did not identify evidence for a difference in terms of mortality. Physical exercise added to standard care might improve fatigue and depression. Currently, there is inconclusive evidence regarding QoL, physical functioning, anxiety and SAEs .
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. To enhance comparability of study data, development and implementation of core sets of measuring devices would be helpful.
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.
In this update of the original review (published in 2014) our main objective was to re-evaluate the efficacy, safety and feasibility of aerobic physical exercise for adults suffering from haematological malignancies considering the current state of knowledge.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2018, Issue 7) and MEDLINE (1950 to July 2018) trials registries (ISRCTN, EU clinical trials register and clinicaltrials.gov) and conference proceedings. We did not apply any language restrictions. Two review authors independently screened search results, disagreements were solved by discussion.
We included randomised controlled trials (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 as well as studies assessing outcomes without any clinical impact.
Two review authors independently screened search results, extracted data and assessed the quality of trials. We used risk ratios (RRs) for adverse events, mortality and 100-day survival, standardised mean differences (SMD) for quality of life (QoL), fatigue, and physical performance, and mean differences (MD) for anthropometric measurements.
In this update, nine trials could be added to the nine trials of the first version of the review, thus we included eighteen RCTs involving 1892 participants. Two of these studies (65 participants) did not provide data for our key outcomes (they analysed laboratory values only) and one study (40 patients) could not be included in the meta-analyses, as results were presented as changes scores only and not as endpoint scores. One trial (17 patients) did not report standard errors and could also not be included in meta-analyses. The overall potential risk of bias in the included 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 eight 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 overall survival (OS) was only reported in one of these studies. The study authors found no evidence for a difference between both arms (RR = 0.67; P = 0.112). Six trials (one trial with four arms, analysed as two sub-studies) reported numbers of deceased participants during the course of the study or during the first 100 to 180 days. For the outcome mortality, there is no evidence for a difference between participants exercising and those in the control group (RR 1.10; 95% CI 0.79 to 1.52; P = 0.59; 1172 participants, low-certainty evidence).
For the following outcomes, higher numbers indicate better outcomes, with 1 being the best result for the standardised mean differences. Eight studies analysed the influence of exercise intervention on QoL. It remains unclear, whether physical exercise improves QoL (SMD 0.11; 95% CI -0.03 to 0.24; 1259 participants, low-certainty evidence). There is also no evidence for a difference for the subscales physical functioning (SMD 0.15; 95% CI -0.01 to 0.32; 8 trials, 1329 participants, low-certainty evidence) and anxiety (SMD 0.03; 95% CI -0.30 to 0.36; 6 trials, 445 participants, very low-certainty evidence). Depression might slightly be improved by exercising (SMD 0.19; 95% CI 0.0 to 0.38; 6 trials, 445 participants, low-certainty evidence). There is moderate-certainty evidence that exercise probably improves fatigue (SMD 0.31; 95% CI 0.13 to 0.48; 9 trials, 826 patients).
Six trials (435 participants) investigated serious adverse events. We are very uncertain, whether additional exercise leads to more serious adverse events (RR 1.39; 95% CI 0.94 to 2.06), based on very low-certainty evidence.
In addition, we are aware of four ongoing trials. However, none of these trials stated, how many patients they will recruit and when the studies will be completed, thus, potential influence of these trials for the current analyses remains unclear.