European Journal of Oncology Nursing 18 (2014) 175e182
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European Journal of Oncology Nursing journal homepage: www.elsevier.com/locate/ejon
Review of attrition and adherence in exercise studies following hematopoietic stem cell transplantation Eileen Danaher Hacker*, Maral Mjukian University of Illinois at Chicago, College of Nursing (M/C 802), Department of Biobehavioral Health Science, 845 S. Damen Avenue, Chicago, IL 60612, USA
a b s t r a c t Keywords: Hematopoietic stem cell transplantation Exercise adherence Subject attrition
Purpose: Implementing exercise programs in people receiving high-dose chemotherapy followed by bone marrow (BMT) or hematopoietic stem cell transplantation (SCT) presents unique challenges. This review examines subject attrition rates and reasons for attrition as well as adherence to exercise interventions following BMT/SCT. Methods: Studies published between January 1985 and December 2012 that prospectively tested an exercise intervention following BMT or SCT were included in the review. Evaluation criteria included: (1) exercise modality; (2) the amount of supervision required to implement the intervention; (3) timing of the intervention; (4) subject attrition rates and reasons for attrition; and (5) exercise adherence rates. Results: Of the 20 studies reviewed, most tested an aerobic exercise intervention or a combination of aerobic and strength training. Supervised exercise sessions were more commonly used than unsupervised sessions. The overall attrition rate was 18% for the 998 subjects enrolled in the studies. Major reasons for attrition included death, change in health status, protocol issues, personal issues with subjects, and lost to follow-up/no reason provided. Authors of supervised exercise programs rarely published exercise adherence information. Unsupervised exercise programs relied mainly on self-report to document adherence. Conclusion: Exercise research following BMT/SCT is becoming more sophisticated as researchers build upon the expanding literature base. Questions regarding subject attrition and adherence to exercise interventions must be addressed to identify interventions that are likely to be successful when translated into clinical practice. Subject attrition from exercise studies following BMT/SCT is relatively low. Adherence information for exercise interventions needs to be regularly addressed. Ó 2013 Elsevier Ltd. All rights reserved.
Introduction The health benefits of exercise are now universally accepted although many people struggle with incorporating exercise into their daily lives (Carlson et al., 2010). In an effort to promote increased physical activity and exercise, the Department of Health and Human Services published the first-ever, Physical Activity Guidelines for Americans (“2008 Physical activity guidelines for Americans,” 2008). Simultaneously, interest in the health benefits of exercise among cancer patients has intensified with over 80 randomized clinical trials published (Speck et al., 2010). Some of the documented beneficial effects of exercise include improved functional capacity (Adamsen et al., 2009), improvement in walking ability in exercisers (Yeo et al., 2012), reduced fatigue (Brown et al., 2011; Cramp and Byron-Daniel, 2012; Mishra et al.,
* Corresponding author. Tel.: þ1 312 996 7924; fax: þ1 312 996 4979. E-mail address: [email protected] (E.D. Hacker). 1462-3889/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejon.2013.10.013
2012a; Schwartz et al., 2001), decreased psychological distress (Midtgaard et al., 2005; Mishra et al., 2012a), and improved quality of life (Courneya et al., 2009; Mishra et al., 2012b; Mishra et al., 2012a). Implementing an exercise program in people with cancer who have received high dose chemotherapy followed by bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (SCT) presents unique challenges. These challenges differ and may be dependent upon a number of factors such as the underlying cancer diagnosis, type of transplant (autologous, allogeneic, matched unrelated donor, or cord), associated medical conditions, such as graft versus host disease, and/or point in the transplant trajectory when the exercise program is implemented. In addition, factors unrelated to cancer or BMT/SCT influence exercise adoption. For example, desire to exercise, time to exercise, and belief in the ability to exercise influence participation and adherence to an exercise program (Arikawa et al., 2012; Courneya et al., 2004, 2012). Exercise requires work and active participation on the part of the individual. In a research setting, the perceived amount of work
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and burden associated with the exercise program impacts the potential subject’s decision to participate in an exercise study. Furthermore, the perceived subject burden influences the subject’s desire and/or willingness to continue participation in the study. In people with cancer, this perceived subject burden may be further complicated by cancer and/or treatment related side effects. Following high-dose chemotherapy and BMT or SCT, perceived subject burden becomes even more important given the intensive nature of the treatment. In exercise studies involving people receiving this intensive cancer therapy, minimizing subject attrition and maintaining adherence are two of the biggest challenges facing researchers who are attempting to evaluate the benefits of an exercise intervention. While the benefits of exercise interventions in people undergoing SCT have been reviewed elsewhere (Wiskemann and Huber, 2008), patient attrition rates and adherence to exercise interventions with SCT have not. This information is important to researchers attempting to design a study, as exercise intervention studies are labor-, cost-, and time-intensive. Furthermore, little information is available to assist researchers in determining subject attrition rates and reasons for the attrition following BMT or SCT. The purpose of this review of the literature is to examine subject attrition rates and reasons for attrition as well as adherence to exercise interventions in people who have received high-dose chemotherapy followed by BMT/SCT. For this review of the literature, subject attrition is defined as subjects who were enrolled in the study but failed to complete all research activities or withdrew from the study for any reason. Exercise adherence is defined as the degree to which the BMT/SCT patient is able to implement and carry out the exercise prescription. Materials and methods Publications included in this review were identified through literature searches of PubMed, Embase, and CINAHL from January 1985 through December 2012, using the index terms “bone marrow transplantation,” “hematopoietic stem cell transplantation” “cancer” and “exercise”. In addition, the references of the studies obtained through computer indexing were examined to locate any additional articles. Meeting abstracts and unpublished studies were not included in the review. This review was limited to adult cancer patients and articles published in English. Initial phase The integrative review of the literature was conducted in two phases. The purpose of the initial phase was to provide an overall sense of the literature focused on exercise in people with cancer that received high-dose chemotherapy followed by BMT or SCT. In the initial phase, all retrieved abstracts were reviewed to determine the type of publication. Abstracts were classified as: (1) exercise intervention studies; (2) studies related to exercise and/or BMT or SCT that did not prospectively test an exercise intervention; (3) integrative reviews of exercise intervention studies in bone marrow or hematopoietic stem cell transplant patients; or (4) other types of reviews articles (i.e., clinical reviews, case reports, etc.). Second phase In the second phase of the literature review, full articles were retrieved and reviewed for all the abstracts classified as research testing an exercise intervention in BMT or SCT. The purpose of the second phase of the review was to provide an in-depth analysis of subject attrition and adherence to exercise interventions. Research articles meeting the following criteria were included in the second
phase of the review: (1) study employed people who had undergone a BMT or SCT; and, (2) study prospectively tested the effects of an exercise intervention on a specified outcome as determined by the investigator(s). The nature of the outcome variable(s) was not limited and included physiological, psychological, and social variables. All studies meeting these predefined criteria were evaluated to determine: 1. The type of exercise intervention: aerobic exercise, strength training, stretching, or a combination of modalities. 2. The amount of supervision required to implement the exercise intervention. 3. Timing of the exercise intervention. 4. Subject attrition rates, defined as the stated number of people who enrolled in the study compared to the final sample size, and the reasons for subject attrition. 5. Adherence rates for supervised, unsupervised or combination (supervised and unsupervised) programs. Results Initial phase: overall classification of articles in the exercise and bone marrow/stem cell transplantation literature One hundred and twenty-seven articles were retrieved from the literature search. The classification of abstracts retrieved during phase 1 is illustrated in Fig. 1. Briefly, the majority of articles were classified as research, but did not prospectively test an exercise intervention (n ¼ 75; 59%). This was followed by review articles, such as clinical reviews, exercise intervention studies, case reports, and finally, integrative reviews. Important to this paper, 20 abstracts (16%) were classified as exercise intervention studies. Second phase: exercise intervention studies in bone marrow/ hematopoietic stem cell transplantation The full articles for the 20 abstracts classified as research prospectively testing an exercise intervention following BMT or SCT were retrieved and reviewed. Studies using the same sample but reporting different findings in multiple journals were only included once. Fifteen of the 20 articles met the defined inclusion criteria of prospectively testing an exercise intervention. An additional five studies were identified by reviewing reference lists of retrieved articles, bringing the total number of studies included in the review to 20 (Table 1). Type of exercise and amount of supervision required The majority of studies tested an aerobic exercise intervention (n ¼ 7; 35%) or a combination of aerobic and strength training
Exercise Intervention Studies Exercise No Intervention
Integrated Review
Other Review Articles ( case reports, clincial revies and ect..)
Fig. 1. Results of initial review of exercise in BMT or SCT abstracts (n ¼ 127 abstracts).
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Table 1 Exercise intervention studies in bone marrow or hematopoietic stem cell transplantation recipients. Study
Exercise intervention
Amount of supervision
Sample sizea
Baumann et al., 2010
Aerobic
Supervised
N ¼ 64 Allogeneic and N ¼ 12 Allogeneic N ¼ 24 Autologous N ¼ 135 Autologous N ¼ 40 Allogeneic N ¼ 100 Allogeneic N ¼ 20 Allogeneic and N ¼ 70 Autologous N ¼ 36 Autologous N ¼ 19 Allogeneic and N ¼ 10 Allogeneic and N ¼ 12 Autologous N ¼ 26 Allogeneic N ¼ 42 Allogeneic N ¼ 42 Allogeneic N ¼ 131 Allogeneic and N ¼ 32 Allogeneic N ¼ 61 Allogeneic N ¼ 17 Allogeneic and N ¼ 105
Carlson et al., 2006
Aerobic
Supervised
Coleman et al., 2003
Unsupervised
Cunningham et al., 1986
Stretching, Aerobic & Strength Training Stretching, Aerobic & Strength Training Strength Training
Supervised
DeFor et al., 2007
Aerobic
Combination
Dimeo et al., 1996
Aerobic
Supervised
Coleman et al., 2008
Unsupervised
Dimeo et al., 1997a
Aerobic
Supervised
Dimeo et al., 1997b
Aerobic
Supervised
Hacker et al., 2011a
Strength Training
Combination
Hacker et al., 2011b Hayes et al., 2003, 2004a, 2004b Inoue et al., 2010 Jarden et al., 2009 Kim and Kim, 2006 Knols et al., 2011 Mello et al., 2003 Shelton et al., 2009 Wilson et al., 2005 Wiskemann et al., 2011 Totals
Strength Training Aerobic and Strength Training Aerobic and Strength Training Aerobic and Strength Training Strength training Aerobic and Strength Training Aerobic and Strength Training Aerobic and Strength Training Aerobic Aerobic and Strength Training
Combination Supervised Supervised Unsupervised Supervised Combination Supervised Supervised Unsupervised Combination
N ¼ 998
Number (%) completers
Design
Timing of intervention
49 (77%)
RCTb
Acute recovery
12 (100%)
QEc
Long-term recovery
13(54%)
RCT
Acute recovery
120(89%)
RCT
Acute recovery
30(75%)
RCT
Acute recovery
14(70%)
QE
Acute recovery
64(91%)
RCT
Acute recovery
32(89%)
QE
Acute recovery
17(90%)
RCT
Acute recovery
10(100%)
QE
Acute recovery
12(100%)
QE
Acute recovery
26(100%)
QE
Acute recovery
34(81%)
RCT
Acute recovery
35(83%)
RCT
Acute recovery
105(80%)
RCT
Acute recovery
18(56%)
RCT
Acute recovery
53(87%)
RCT
Acute recovery
13(77%)
QE
80(76%)
RCT
Acute and long-term recovery Acute recovery
autologous
81(81%)
autologous
autologous autologous
autologous
autologous
818(82%)
Note: Acute recovery denotes within the first year following bone marrow or hematopoietic stem cell transplantation. Long-term recovery denotes more than one year post bone marrow or hematopoietic stem cell transplantation. a Sample size indicates number enrolled. The number of subjects that complete the program may be different. b RCT: randomized controlled trial. c QE: quasi-experimental.
(n ¼ 7; 35%). The aerobic exercise interventions varied and included activities such as stationary bicycling, walking, or treadmill walking. Other exercise modalities tested included: (1) ¼ strength training (n ¼ 4; 20%) or, (2) combination of stretching, aerobic and strength training (n ¼ 2; 10%). The strength training interventions used elastic bands for resistance and weights. The amount of supervision required to implement the exercise intervention was examined to determine how much labor was involved in implementing the intervention. Supervised exercise sessions (55%; n ¼ 11) were most common while unsupervised sessions least common (20%; n ¼ 4). Five studies (25%) used a combination approach by supervising some sessions with study participants completing other sessions unsupervised. Subject attrition Overall, the 20 studies enrolled 998 subjects and retained 818 subjects (82%). The mean sample size at enrollment across all studies was 49.9 (SD ¼ 39.38) with an average of 40.9 (SD ¼ 33.05) completing research activities. There was a wide variation in sample sizes, however, with initial sample sizes ranging from 10 to 135 subjects and the number of subjects completing study
activities ranging from 10 to 120 subjects (Fig. 2). The patient attrition rate for the exercise intervention studies ranged from 0% to 44%. Few studies retained 100% of the enrolled subjects (n ¼ 4 studies) and these studies enrolled 26 participants each. Three of the four studies were supervised with two conducted in the acute recovery phase (less than a year post transplant) and the other in long-term survivors (more than a year post transplant). Seven (35%) of the exercise intervention studies retained less than 80% of their original sample subjects with nine studies (45%) retaining 80e92%. The reasons for subject attrition cited in the studies were examined, summarized, and rank-ordered (Table 2). A total of 180 subjects withdrew from the 20 studies. Five major categories for subject attrition were identified. These included: (1) death; (2) change in subject’s health status; (3) issues related to the research protocol; (4) personal issues with subjects; and, (5) no reason provided. The most common reason for subject attrition in the exercise intervention studies was death with 79 subjects (44% of subject attrition) expiring during the course of the study. Importantly, the causes of the death in these subjects were not attributed to the exercise intervention. Another 44 subjects (24% of subject
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Fig. 2. Subject attrition in exercise intervention studies following BMT/SCT.
attrition) were either removed from the studies or chose to leave the studies after a change in their health condition, such as disease progression or disease recurrence. Protocol issues, such as inability to collect data at specified time points or cancer chemotherapy treatment not being received, were cited as the reason for attrition in 21 subjects (12%) while another 14% (n ¼ 23 subjects) did not provide a reason. Finally, 5 subjects (3%) withdrew from the studies citing personal issues, such as being too busy. It is important to note that not all subjects who chose to discontinue participation or were removed from the studies were assigned to the exercise group. Forty eight percent of the subjects were assigned to the exercise arm (n ¼ 87) while 36% (n ¼ 64) were assigned to the control arm (Table 2). The treatment allocation for the remaining subjects who did not complete research activities was not specified (16%). Adherence to exercise interventions Methods to measure adherence to the exercise intervention as well as rates of adherence were examined broadly in the 20 studies (Table 3). In studies employing a supervised approach, adherence to the exercise interventions can be readily evaluated by determining the number of exercise sessions completed or the percentage of the exercise prescription completed. In the 11 studies that employed a supervised exercise program, more than two-thirds (n ¼ 8; 73%) did not report adherence rates. Two supervised studies reported adherence rate as mean attendance at exercise sessions (75% and 90%). One study reported an adherence measure (attendance) but did not report the adherence rate. Five studies combined a supervised approach with an unsupervised exercise component. Four of the five studies reported adherence rates while one did not. Three studies reported adherence as the ability to successfully execute the prescribed exercise (range, 50e100% exercise adherence) while one study reported that 24% of subjects followed the suggested routine (prescribed exercise intervention) 100% of the time.
All of the unsupervised exercise intervention studies (n ¼ 4) relied on patient self-report in the form of logs or diaries to document adherence to the exercise program. Even though the methods to measure adherence were reported, the actual adherence rates were only reported in one unsupervised study. This study reported a mean adherence rate of 75% over the six month duration of the study. Discussion The ever-expanding literature base investigating links between exercise and cancer reflects the substantial interest in the role that exercise may play in reducing the incidence of cancer, cancer recurrence, and cancer- or cancer treatment-related side effects. The first article evaluating an exercise intervention following BMT was published in 1986 (Cunningham et al., 1986). By December 2012, researchers had implemented exercise interventions in a variety of cancer populations across the cancer trajectory, including those receiving high dose chemotherapy followed by BMT or SCT. It is no longer a question of whether exercise is beneficial, as the research base supports the use of exercise for achieving a wide spectrum of health-related outcomes (Mishra et al., 2012a, 2012b). Researchers now ask more sophisticated questions, such as what is the most appropriate exercise prescription for achieving healthrelated outcomes in people with cancer; what type of exercise (aerobic, strength training, stretching, or a combination) is most appropriate to implement across a variety of settings; and what is the most efficient doseeresponse? Importantly, questions regarding subject attrition and adherence to exercise interventions must be addressed to identify those interventions that are likely to be successful when translated into clinical practice. Implementing an exercise study in people who have received high dose chemotherapy followed by BMT or SCT presents unique challenges that impact subject retention as well as adherence to the exercise intervention. Exercise studies can be very expensive to
E.D. Hacker, M. Mjukian / European Journal of Oncology Nursing 18 (2014) 175e182 Table 2 Cited reasons for subject attrition. Reason and number of subjects
Treatment allocation
Death (not related to exercise study) (n¼79)
Ex ¼ 33 C ¼ 33 NS ¼ 13
Change in subject’s health status (n¼44) Medical complications Disease progression Chemotherapy induced cardiomyopathy Comorbid other than cancer Developed Complications Progressive Disease Recurrence of active disease Avascular necrosis
EX ¼ 26 C ¼ 14 NS ¼ 4
Protocol issues (n ¼ 21) Withdrew from multiple myeloma treatment protocol Refused to continue participation Did not complete the study Dropped out prior to allogeneic SCT Refused to continue with treatment assignment Did not agree to allocation Refused before completing post test
EX ¼ 7 C ¼ 10 NS ¼ 4
Personal issues (n ¼ 13) Busy with work Lost interest Moved away Refused before completing the post test
EX ¼ 4 C¼1
Reasons not provided (n ¼ 23) Left study before 2nd data collection point (reason not reported) Left study before 3rd data collection point (reason not reported) Dropped Out Withdrew from study
EX ¼ 17 C¼6
Miscellaneous (n ¼ 8) Reason for attrition not assigned as exact number of subjects per reason not specified. Subjects dropped for personal and medical reasons.
NS ¼ 8
EX e Exercise group; C e Control group; NS e Not Specified.
implement, especially if specialized equipment (such as treadmills or metabolic carts) is needed and/or if supervision is required for testing subjects’ performance status and/or to implement the exercise intervention. Subject attrition is always a concern for researchers and should be particularly concerning to researchers interested in testing an exercise intervention. This paper provides an attempt to quantify subject attrition and to determine the reasons for subject attrition in exercise studies involving people who have received BMT or SCT. This information is important to help researchers determine whether subject attrition rates in their studies are consistent with studies using similar interventions and populations. This information also provides both researchers and clinicians with the data that they may need to estimate projected sample sizes and address feasibility and acceptability issues, particularly if the research is to be translated into clinical practice. In this review of prospective BMT/SCT exercise intervention studies, subject retention rate was surprisingly high (82%) although there was variation. The high retention rate likely reflects widespread acceptance of exercise as beneficial. For those people who do not like to exercise and/or do not feel that they can readily master the activity, they may refuse participation right from the outset, thus, limiting subject attrition. For those who agree to participate, exercise may be seen as having direct health benefits (especially if assigned to the exercise arm) promoting continued
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participation. In addition, subjects may perceive exercise as an achievable health behavior that is within their control, contributing to their willingness to continue participation (Courneya et al., 2005). High retention rates in the BMT/SCT exercise studies may also reflect the researchers’ ability to tailor the exercise interventions appropriately to this unique population. For instance, conducting the exercise program during regularly scheduled clinic appointments is an opportune time for subjects to exercise under supervision while reducing subject burden associated with additional research visits. We have found this approach to be well received among hematopoietic stem cell transplant patients (Hacker et al., 2011a). The importance of providing reasons for subject attrition in BMT/SCT exercise studies cannot be overestimated. When reasons for subject attrition are not provided, readers are essentially left to their own devices for conjuring up a reason. Was the exercise intervention too difficult for the subjects? Was the subject burden too much if subjects were required to attend a set number of supervised exercise sessions per week? Were the subjects too ill to participate in the exercise program? These questions can be simply answered just by including subject attrition information in the published report. In this review, death was the most common reason for subject attrition. The number of deaths in the exercise arm was approximately the same as the control arm. Importantly, the exercise intervention did not lead to death in any of the subjects assigned to the exercise arm. Not surprisingly, a change in the subject’s health status was the second most common reason for subject attrition in the BMT/SCT exercise intervention studies. This supports the notion that implementing an exercise program in people following BMT or SCT is challenging as disease progression or ability to tolerate therapy cannot always be predicted. For example, this review identified disease recurrence, disease progression, chemotherapyinduced cardiomyopathy, and avascular necrosis as a few examples of changes in health status that resulted in subject attrition. Unfortunately, researchers are unable to predict with complete accuracy those who will develop complications or expire prior to enrollment. Establishing appropriate inclusion criteria for an exercise study following BMT/SCT helps to increase the likelihood of subject retention, although not in all cases. Losing subjects to changes in health status may be more problematic in studies that involve people in the first year following BMT/HSCT compared to long-term survivors as changes in health status tend to occur frequently in the first year post transplant (Pidala et al., 2009). In this review, the majority of exercise intervention studies were conducted in the acute recovery period (during the first year post BMT or SCT). Unfortunately, implementing an exercise intervention may prove difficult during the acute recovery phase, even if the exercise intervention is only mildly intense. On the other hand, waiting until all therapy is completed prior to initiating an exercise program may lead to even more physical deconditioning following BMT/SCT, especially for those who lived a sedentary life prior to the intensive therapy. One solution to mitigate the problem with subject attrition due to changing health status is to tailor the exercise interventions to the individual’s capacity with frequent periods of reassessment. This is an area of inquiry that is ripe for research and will help determine the appropriate time to implement an exercise intervention to enhance health-related outcomes and decrease the potential for subject attrition in exercise studies. Conducting clinical research requires flexibility to adapt to dynamic situations. Implementing an exercise intervention in a dynamic clinical environment is bound to result in protocol implementation issues that also impact subject attrition. This review identifies some of the methodological issues associated with subject attrition in BMT or HSCT exercise studies, such as inability to
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Table 3 Adherence to exercise interventions. Study
Amount of supervision
Adherence to exercise intervention reported
Baumann et al., 2010 Carlson et al., 2006 Coleman et al., 2003
Supervised Supervised Unsupervised
No Yes Yes
Coleman et al., 2008
Unsupervised
Yes
Cunningham et al., 1986 DeFor et al., 2007
Supervised Combination
No Yes
Dimeo et al., 1996 Dimeo et al., 1997a Dimeo et al., 1997b Hacker et al., 2011a
Supervised Supervised Supervised Combination
No No No Yes
Hacker et al., 2011b
Combination
Yes
Hayes et al., 2003, 2004a, 2004b Inoue et al., 2010 Jarden et al., 2009 Kim and Kim, 2006 Knols et al., 2011 Mello et al., 2003 Shelton et al., 2009
Supervised
Yes
Supervised Unsupervised Supervised Combination Supervised Supervised
No Yes No No No Yes
Wilson et al., 2005 Wiskemann et al., 2011
Unsupervised Combination
Yes Yes
complete pre- and post-testing sessions or failure to agree to treatment allocations. Failure to agree to treatment allocation and/ or diffusion of treatment effect (subjects in the control arm engaging in exercise behaviors) may be particularly troublesome in BMT or SCT studies given the widespread acceptance of the benefits of exercise. Furthermore, it would be considered unethical to tell a subject assigned to the control arm not to exercise. Several solutions to this problem may be helpful such as wait listing the exercise component or comparing exercise modalities with different mechanisms of action. Regardless of the solution, it is critical to ask about exercise behaviors in subjects in the control arm. For example, in our pilot randomized controlled trial, two of the nine subjects assigned to the usual activity arm exercised although they did not begin exercising until four weeks later than the exercise arm (Hacker et al., 2011a). Very few subjects withdrew from the BMT/HSCT because of personal issues, such as too busy with work. This suggests that subjects, in general, are able to realistically determine whether or not they have adequate resources at their disposal to participate and investigators have provided subjects with realistic information regarding burden of participating in an exercise intervention study. While subject attrition rates provide readers with specifics regarding subjects who fail to complete research activities, information regarding adherence to the exercise program is also needed. For instance, researchers and clinicians need to know how much exercise is needed to sustain a specified effect. What exercise prescription yields the most benefit and results in the greatest adherence? What
Methods to enhance and/or monitor exercise adherence
Adherence rates
Completion of exercise sessions. Self-report of exercise with weekly review of exercise logs.
90% On average, the exercise group completed the six-month exercise prescription 75% of the time
Self-report in exercise logs with periodic personal interviews to enhance compliance. Self-report in exercise log or diary.
10(24%) followed the suggested routine 100% of the time
Self-report using exercise logs for unsupervised visits. Completion of exercise sessions for supervised visits
Exercising 3 times per week ranged from 50 to 100% over the six week intervention. Exercising 1e2 times per week ranged from 0 to 38% over the six week intention. Only one patient did not exercise in one week. By Week 6, 60% exercising 3 times per week, 20% exercising 1e2 times per week
Self-report using exercise logs for unsupervised visits. Completion of exercise sessions for supervised visits Attendance at exercise sessions
Self-report in exercise logs
Completion of exercise sessions. Self-report diary Self-report in exercise logs
Subjects completed an average of 9 out 12 exercise sessions 87.5% before HSCT, 83% during inpatient hospitalization, and 91.3% 6e8 weeks following hospital discharge.
is considered to be an acceptable adherence rate? Should the same standard for adherence rates exist for supervised versus unsupervised programs? High-intensity compared to mild-intensity? This review suggests that researchers frequently neglect to publish adherence rates to supervised exercise interventions, as more than two-thirds of the supervised exercise intervention studies did not report this information. The reasons for this are unclear. Perhaps there is an assumption that unpublished adherence data reflect 100% completion of all exercise activities. Given the ease to collect adherence to exercise interventions, particularly in supervised exercise intervention studies, it is essential to address this issue in publication so that clinicians and researchers can determine the likelihood of successful implementation of the exercise intervention in their BMT or SCT populations. Researchers that employ an unsupervised or a combination approach to an exercise study may find it more difficult to collect adherence data, particularly if relying only on self-report information. Problems associated with self-report diaries have been documented elsewhere, and there is little reason to believe that these problems would be different for an exercise intervention study involving BMT or SCT patients (Stone et al., 2002). For instance, forgetting to document an exercise session and/or documenting all the sessions in one sitting are just two of the many potential problems when using self-reporting mechanisms. In this review of the literature, all unsupervised exercise intervention studies relied on self-report to examine adherence to the exercise intervention. Supplementing subjective data (self-report) with
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objective data (such as pedometers or accelerometers) may provide additional information related to the fidelity of the intervention, however, most objective devices, such as accelerometers, are not able to specifically pinpoint the type of exercise being conducted, only the increase in physical activity. Even so, adherence data are particularly important, as they provide doseeresponse exercise information. In this review, adherence to the exercise prescription ranged from 50% to 100%, illustrating the wide variation for adhering to exercise interventions and the importance for noting this information to evaluate dose-responsiveness. Conclusions Exercise research following BMT or SCT is becoming more sophisticated as researchers build upon the expanding literature base. In general, subject attrition from exercise studies involving BMT or SCT patients is relatively low, although there is wide variation. The reasons for subject attrition include death, changes in health status, issues related to the research protocol, personal issues with subjects, and loss to follow-up or no reason provided. Even though death was the single largest cited reason for subject attrition in this review, none of the deaths were the result or related to the exercise intervention. Little information regarding adherence to supervised exercise interventions following BMT or SCT is provided in the literature, even though this information is relatively easy to collect especially for supervised exercise interventions. Collecting adherence data in unsupervised exercise studies may be more difficult, given the potential problems with self-report data. Future studies may consider adding an objective measure of physical activity, such as pedometers or accelerometers to supplement this self-reported adherence data. Conflict of interest statement None declared. References Adamsen, L., Quist, M., Andersen, C., Moller, T., Herrstedt, J., Kronborg, D., et al., 2009. Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial. British Medical Journal 339, b3410. Arikawa, A.Y., O’Dougherty, M., Kaufman, B.C., Schmitz, K.H., Kurzer, M.S., 2012. Attrition and adherence of young women to aerobic exercise: lessons from the WISER study. Contemporary Clinical Trials 33 (2), 298e301. http://dx.doi.org/ 10.1016/j.cct.2011.11.017. Baumann, F.T., Kraut, L., Schule, K., Bloch, W., Fauser, A.A., 2010. A controlled randomized study examining the effects of exercise therapy on patients undergoing haematopoietic stem cell transplantation. Bone Marrow Transplantation 45 (2), 355e362. http://dx.doi.org/10.1038/bmt.2009.163. Brown, J.C., Huedo-Medina, T.B., Pescatello, L.S., Pescatello, S.M., Ferrer, R.A., Johnson, B.T., 2011. Efficacy of exercise interventions in modulating cancerrelated fatigue among adult cancer survivors: a meta-analysis. Cancer Epidemiology, Biomarkers & Prevention 20 (1), 123e133. http://dx.doi.org/10.1158/ 1055-9965.EPI-10-0988. Carlson, L.E., Smith, D., Russell, J., Fibich, C., Whittaker, T., 2006. Individualized exercise program for the treatment of severe fatigue in patients after allogeneic hematopoietic stem-cell transplant: a pilot study. Bone Marrow Transplantation 37 (10), 945e954. Carlson, S.A., Fulton, J.E., Schoenborn, C.A., Loustalot, F., 2010. Trend and prevalence estimates based on the 2008 Physical Activity Guidelines for Americans. American Journal of Preventative Medicine 39 (4), 305e313. http://dx.doi.org/ 10.1016/j.amepre.2010.06.006. Coleman, E.A., Coon, S., Hall-Barrow, J., Richards, K., Gaylor, D., Stewart, B., 2003. Feasibility of exercise during treatment for multiple myeloma. Cancer Nursing 26 (5), 410e419. Coleman, E.A., Coon, S.K., Kennedy, R.L., Lockhart, K.D., Stewart, C.B., Anaissie, E.J., et al., 2008. Effects of exercise in combination with epoetin alfa during highdose chemotherapy and autologous peripheral blood stem cell transplantation for multiple myeloma. Oncology Nursing Forum 35 (3), E53eE61. Courneya, K.S., Friedenreich, C.M., Quinney, H.A., Fields, A.L., Jones, L.W., Fairey, A.S., 2004. Predictors of adherence and contamination in a randomized trial of exercise in colorectal cancer survivors. Psychooncology 13 (12), 857e866.
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Courneya, K.S., Friedenreich, C.M., Quinney, H.A., Fields, A.L., Jones, L.W., Vallance, J.K., et al., 2005. A longitudinal study of exercise barriers in colorectal cancer survivors participating in a randomized controlled trial. Annals of Behavioral Medicine 29 (2), 147e153. Courneya, K.S., Karvinen, K.H., McNeely, M.L., Campbell, K.L., Brar, S., Woolcott, C.G., et al., 2012. Predictors of adherence to supervised and unsupervised exercise in the Alberta Physical Activity and Breast Cancer Prevention Trial. Journal of Physical Acivity & Health 9 (6), 857e866. Courneya, K.S., Sellar, C.M., Stevinson, C., McNeely, M.L., Peddle, C.J., Friedenreich, C.M., et al., 2009. Randomized controlled trial of the effects of aerobic exercise on physical functioning and quality of life in lymphoma patients. Journal of Clinical Oncology 27 (27), 4605e4612. http://dx.doi.org/ 10.1200/JCO.2008.20.0634. Cramp, F., Byron-Daniel, J., 2012. Exercise for the management of cancer-related fatigue in adults. Cochrane Database of Systematic Reviews 11, CD006145. http://dx.doi.org/10.1002/14651858.CD006145.pub3. Cunningham, B.A., Morris, G., Cheney, C.L., Buergel, N., Aker, S.N., Lenssen, P., 1986. Effects of resistive exercise on skeletal muscle in marrow transplant recipients receiving total parenteral nutrition. Journal of Parenteral and Enteral Nutrition 10 (6), 558e563. DeFor, T.E., Burns, L.J., Gold, E.M., Weisdorf, D.J., 2007. A randomized trial of the effect of a walking regimen on the functional status of 100 adult allogeneic donor hematopoietic cell transplant patients. Biology of Blood and Marrow Transplantation 13 (8), 948e955. Dimeo, F., Bertz, H., Finke, J., Fetscher, S., Mertelsmann, R., Keul, J., 1996. An aerobic exercise program for patients with haematological malignancies after bone marrow transplantation. Bone Marrow Transplantation 18 (6), 1157e1160. Dimeo, F., Fetscher, S., Lange, W., Mertelsmann, R., Keul, J., 1997a. Effects of aerobic exercise on the physical performance and incidence of treatment-related complications after high-dose chemotherapy. Blood 90 (9), 3390e3394. Dimeo, F., Tilmann, M.H.N., Bertz, H., Kanz, L., Mertelsmann, R., Keul, J., 1997b. Aerobic exercise in the rehabilitation of cancer patients after high dose chemotherapy and autologous peripheral stem cell transplantation. Cancer 79, 1717e1722. Hacker, E.D., Larson, J., Kujath, A., Peace, D., Rondelli, D., Gaston, L., 2011a. Strength training following hematopoietic stem cell transplantation. Cancer Nursing 34 (3), 238e249. Hacker, E.D., Larson, J.L., Peace, D., 2011b. Exercise in patients receiving hematopoietic stem cell transplantation: lessons learned and results from a feasibility study. Oncology Nursing Forum 38 (2), 216e223. Hayes, S., Davies, P.S., Parker, T., Bashford, J., 2003. Total energy expenditure and body composition changes following peripheral blood stem cell transplantation and participation in an exercise programme. Bone Marrow Transplantation 31 (5), 331e338. Hayes, S.C., Davies, P.S., Parker, T.W., Bashford, J., Green, A., 2004a. Role of a mixed type, moderate intensity exercise programme after peripheral blood stem cell transplantation. British Journal of Sports Medicine 38 (3), 304e309 discussion 309. Hayes, S., Davies, P.S., Parker, T., Bashford, J., Newman, B., 2004b. Quality of life changes following peripheral blood stem cell transplantation and participation in a mixed-type, moderate-intensity, exercise program. Bone Marrow Transplantation 33 (5), 553e558. Inoue, J., Ono, R., Okamura, A., Matsui, T., Takekoshi, H., Miwa, M., et al., 2010. The impact of early rehabilitation on the duration of hospitalization in patients after allogeneic hematopoietic stem cell transplantation. Transplantation Proceedings 42 (7), 2740e2744. http://dx.doi.org/10.1016/ j.transproceed.2010.05.153. Jarden, M., Baadsgaard, M.T., Hovgaard, D.J., Boesen, E., Adamsen, L., 2009. A randomized trial on the effect of a multimodal intervention on physical capacity, functional performance and quality of life in adult patients undergoing allogeneic SCT. Bone Marrow Transplantation 43 (9), 725e737. Kim, S.D., Kim, H.S., 2006. A series of bed exercises to improve lymphocyte count in allogeneic bone marrow transplantation patients. European Journal of Cancer Care (Engl) 15 (5), 453e457. Knols, R.H., de Bruin, E.D., Uebelhart, D., Aufdemkampe, G., Schanz, U., StennerLiewen, F., et al., 2011. Effects of an outpatient physical exercise program on hematopoietic stem-cell transplantation recipients: a randomized clinical trial. Bone Marrow Transplantation 46 (9), 1245e1255. Mello, M., Tanaka, C., Dulley, F.L., 2003. Effects of an exercise program on muscle performance in patients undergoing allogeneic bone marrow transplantation. Bone Marrow Transplantation 32 (7), 723e728. Midtgaard, J., Rorth, M., Stelter, R., Tveteras, A., Andersen, C., Quist, M., et al., 2005. The impact of a multidimensional exercise program on self-reported anxiety and depression in cancer patients undergoing chemotherapy: a phase II study. Palliative & Supportive Care 3 (3), 197e208. Mishra, S.I., Scherer, R.W., Geigle, P.M., Berlanstein, D.R., Topaloglu, O., Gotay, C.C., et al., 2012a. Exercise interventions on health-related quality of life for cancer survivors. Cochrane Database of Systematic Reviews 8, CD007566. http:// dx.doi.org/10.1002/14651858.CD007566.pub2. Mishra, S.I., Scherer, R.W., Snyder, C., Geigle, P.M., Berlanstein, D.R., Topaloglu, O., 2012b. Exercise interventions on health-related quality of life for people with cancer during active treatment. Cochrane Database of Systematic Reviews 8, CD008465. http://dx.doi.org/10.1002/14651858.CD008465.pub2.
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Pidala, J., Anasetti, C., Jim, H., 2009. Quality of life after allogeneic hematopoietic cell transplantation. Blood 114 (1), 7e19. Schwartz, A.L., Mori, M., Gao, R., Nail, L.M., King, M.E., 2001. Exercise reduces daily fatigue in women with breast cancer receiving chemotherapy. Medicine & Science in Sports & Exercise 33 (5), 718e723. Shelton, M.L., Lee, J.Q., Morris, G.S., Massey, P.R., Kendall, D.G., Munsell, M.F., et al., 2009. A randomized control trial of a supervised versus a self-directed exercise program for allogeneic stem cell transplant patients. Psychooncology 18 (4), 353e359. Speck, R.M., Courneya, K.S., Masse, L.C., Duval, S., Schmitz, K.H., 2010. An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. Journal of Cancer Survivorship 4 (2), 87e100. http://dx.doi.org/ 10.1007/s11764-009-0110-5. Stone, A.A., Shiffman, S., Schwartz, J.E., Broderick, J.E., Hufford, M.R., 2002. Patient non-compliance with paper diaries. British Medical Journal 324 (7347), 1193e 1194.
Wilson, R.W., Jacobsen, P.B., Fields, K.K., 2005. Pilot study of a home-based aerobic exercise program for sedentary cancer survivors treated with hematopoietic stem cell transplantation. Bone Marrow Transplantation 35 (7), 721e727. Wiskemann, J., Dreger, P., Schwerdtfeger, R., Bondong, A., Huber, G., Kleindienst, N., et al., 2011. Effects of a partly self-administered exercise program before, during, and after allogeneic stem cell transplantation. Blood 117 (9), 2604e2613. Wiskemann, J., Huber, G., 2008. Physical exercise as adjuvant therapy for patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplantation 41 (4), 321e329. Yeo, T.P., Burrell, S.A., Sauter, P.K., Kennedy, E.P., Lavu, H., Leiby, B.E., et al., 2012. A progressive postresection walking program significantly improves fatigue and health-related quality of life in pancreas and periampullary cancer patients. The Journal of the American College of Surgeons 214 (4), 463e475. http:// dx.doi.org/10.1016/j.jamcollsurg.2011.12.017 discussion 475-467.
Contents lists available at ScienceDirect
European Journal of Oncology Nursing journal homepage: www.elsevier.com/locate/ejon
Review of attrition and adherence in exercise studies following hematopoietic stem cell transplantation Eileen Danaher Hacker*, Maral Mjukian University of Illinois at Chicago, College of Nursing (M/C 802), Department of Biobehavioral Health Science, 845 S. Damen Avenue, Chicago, IL 60612, USA
a b s t r a c t Keywords: Hematopoietic stem cell transplantation Exercise adherence Subject attrition
Purpose: Implementing exercise programs in people receiving high-dose chemotherapy followed by bone marrow (BMT) or hematopoietic stem cell transplantation (SCT) presents unique challenges. This review examines subject attrition rates and reasons for attrition as well as adherence to exercise interventions following BMT/SCT. Methods: Studies published between January 1985 and December 2012 that prospectively tested an exercise intervention following BMT or SCT were included in the review. Evaluation criteria included: (1) exercise modality; (2) the amount of supervision required to implement the intervention; (3) timing of the intervention; (4) subject attrition rates and reasons for attrition; and (5) exercise adherence rates. Results: Of the 20 studies reviewed, most tested an aerobic exercise intervention or a combination of aerobic and strength training. Supervised exercise sessions were more commonly used than unsupervised sessions. The overall attrition rate was 18% for the 998 subjects enrolled in the studies. Major reasons for attrition included death, change in health status, protocol issues, personal issues with subjects, and lost to follow-up/no reason provided. Authors of supervised exercise programs rarely published exercise adherence information. Unsupervised exercise programs relied mainly on self-report to document adherence. Conclusion: Exercise research following BMT/SCT is becoming more sophisticated as researchers build upon the expanding literature base. Questions regarding subject attrition and adherence to exercise interventions must be addressed to identify interventions that are likely to be successful when translated into clinical practice. Subject attrition from exercise studies following BMT/SCT is relatively low. Adherence information for exercise interventions needs to be regularly addressed. Ó 2013 Elsevier Ltd. All rights reserved.
Introduction The health benefits of exercise are now universally accepted although many people struggle with incorporating exercise into their daily lives (Carlson et al., 2010). In an effort to promote increased physical activity and exercise, the Department of Health and Human Services published the first-ever, Physical Activity Guidelines for Americans (“2008 Physical activity guidelines for Americans,” 2008). Simultaneously, interest in the health benefits of exercise among cancer patients has intensified with over 80 randomized clinical trials published (Speck et al., 2010). Some of the documented beneficial effects of exercise include improved functional capacity (Adamsen et al., 2009), improvement in walking ability in exercisers (Yeo et al., 2012), reduced fatigue (Brown et al., 2011; Cramp and Byron-Daniel, 2012; Mishra et al.,
* Corresponding author. Tel.: þ1 312 996 7924; fax: þ1 312 996 4979. E-mail address: [email protected] (E.D. Hacker). 1462-3889/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejon.2013.10.013
2012a; Schwartz et al., 2001), decreased psychological distress (Midtgaard et al., 2005; Mishra et al., 2012a), and improved quality of life (Courneya et al., 2009; Mishra et al., 2012b; Mishra et al., 2012a). Implementing an exercise program in people with cancer who have received high dose chemotherapy followed by bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (SCT) presents unique challenges. These challenges differ and may be dependent upon a number of factors such as the underlying cancer diagnosis, type of transplant (autologous, allogeneic, matched unrelated donor, or cord), associated medical conditions, such as graft versus host disease, and/or point in the transplant trajectory when the exercise program is implemented. In addition, factors unrelated to cancer or BMT/SCT influence exercise adoption. For example, desire to exercise, time to exercise, and belief in the ability to exercise influence participation and adherence to an exercise program (Arikawa et al., 2012; Courneya et al., 2004, 2012). Exercise requires work and active participation on the part of the individual. In a research setting, the perceived amount of work
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and burden associated with the exercise program impacts the potential subject’s decision to participate in an exercise study. Furthermore, the perceived subject burden influences the subject’s desire and/or willingness to continue participation in the study. In people with cancer, this perceived subject burden may be further complicated by cancer and/or treatment related side effects. Following high-dose chemotherapy and BMT or SCT, perceived subject burden becomes even more important given the intensive nature of the treatment. In exercise studies involving people receiving this intensive cancer therapy, minimizing subject attrition and maintaining adherence are two of the biggest challenges facing researchers who are attempting to evaluate the benefits of an exercise intervention. While the benefits of exercise interventions in people undergoing SCT have been reviewed elsewhere (Wiskemann and Huber, 2008), patient attrition rates and adherence to exercise interventions with SCT have not. This information is important to researchers attempting to design a study, as exercise intervention studies are labor-, cost-, and time-intensive. Furthermore, little information is available to assist researchers in determining subject attrition rates and reasons for the attrition following BMT or SCT. The purpose of this review of the literature is to examine subject attrition rates and reasons for attrition as well as adherence to exercise interventions in people who have received high-dose chemotherapy followed by BMT/SCT. For this review of the literature, subject attrition is defined as subjects who were enrolled in the study but failed to complete all research activities or withdrew from the study for any reason. Exercise adherence is defined as the degree to which the BMT/SCT patient is able to implement and carry out the exercise prescription. Materials and methods Publications included in this review were identified through literature searches of PubMed, Embase, and CINAHL from January 1985 through December 2012, using the index terms “bone marrow transplantation,” “hematopoietic stem cell transplantation” “cancer” and “exercise”. In addition, the references of the studies obtained through computer indexing were examined to locate any additional articles. Meeting abstracts and unpublished studies were not included in the review. This review was limited to adult cancer patients and articles published in English. Initial phase The integrative review of the literature was conducted in two phases. The purpose of the initial phase was to provide an overall sense of the literature focused on exercise in people with cancer that received high-dose chemotherapy followed by BMT or SCT. In the initial phase, all retrieved abstracts were reviewed to determine the type of publication. Abstracts were classified as: (1) exercise intervention studies; (2) studies related to exercise and/or BMT or SCT that did not prospectively test an exercise intervention; (3) integrative reviews of exercise intervention studies in bone marrow or hematopoietic stem cell transplant patients; or (4) other types of reviews articles (i.e., clinical reviews, case reports, etc.). Second phase In the second phase of the literature review, full articles were retrieved and reviewed for all the abstracts classified as research testing an exercise intervention in BMT or SCT. The purpose of the second phase of the review was to provide an in-depth analysis of subject attrition and adherence to exercise interventions. Research articles meeting the following criteria were included in the second
phase of the review: (1) study employed people who had undergone a BMT or SCT; and, (2) study prospectively tested the effects of an exercise intervention on a specified outcome as determined by the investigator(s). The nature of the outcome variable(s) was not limited and included physiological, psychological, and social variables. All studies meeting these predefined criteria were evaluated to determine: 1. The type of exercise intervention: aerobic exercise, strength training, stretching, or a combination of modalities. 2. The amount of supervision required to implement the exercise intervention. 3. Timing of the exercise intervention. 4. Subject attrition rates, defined as the stated number of people who enrolled in the study compared to the final sample size, and the reasons for subject attrition. 5. Adherence rates for supervised, unsupervised or combination (supervised and unsupervised) programs. Results Initial phase: overall classification of articles in the exercise and bone marrow/stem cell transplantation literature One hundred and twenty-seven articles were retrieved from the literature search. The classification of abstracts retrieved during phase 1 is illustrated in Fig. 1. Briefly, the majority of articles were classified as research, but did not prospectively test an exercise intervention (n ¼ 75; 59%). This was followed by review articles, such as clinical reviews, exercise intervention studies, case reports, and finally, integrative reviews. Important to this paper, 20 abstracts (16%) were classified as exercise intervention studies. Second phase: exercise intervention studies in bone marrow/ hematopoietic stem cell transplantation The full articles for the 20 abstracts classified as research prospectively testing an exercise intervention following BMT or SCT were retrieved and reviewed. Studies using the same sample but reporting different findings in multiple journals were only included once. Fifteen of the 20 articles met the defined inclusion criteria of prospectively testing an exercise intervention. An additional five studies were identified by reviewing reference lists of retrieved articles, bringing the total number of studies included in the review to 20 (Table 1). Type of exercise and amount of supervision required The majority of studies tested an aerobic exercise intervention (n ¼ 7; 35%) or a combination of aerobic and strength training
Exercise Intervention Studies Exercise No Intervention
Integrated Review
Other Review Articles ( case reports, clincial revies and ect..)
Fig. 1. Results of initial review of exercise in BMT or SCT abstracts (n ¼ 127 abstracts).
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Table 1 Exercise intervention studies in bone marrow or hematopoietic stem cell transplantation recipients. Study
Exercise intervention
Amount of supervision
Sample sizea
Baumann et al., 2010
Aerobic
Supervised
N ¼ 64 Allogeneic and N ¼ 12 Allogeneic N ¼ 24 Autologous N ¼ 135 Autologous N ¼ 40 Allogeneic N ¼ 100 Allogeneic N ¼ 20 Allogeneic and N ¼ 70 Autologous N ¼ 36 Autologous N ¼ 19 Allogeneic and N ¼ 10 Allogeneic and N ¼ 12 Autologous N ¼ 26 Allogeneic N ¼ 42 Allogeneic N ¼ 42 Allogeneic N ¼ 131 Allogeneic and N ¼ 32 Allogeneic N ¼ 61 Allogeneic N ¼ 17 Allogeneic and N ¼ 105
Carlson et al., 2006
Aerobic
Supervised
Coleman et al., 2003
Unsupervised
Cunningham et al., 1986
Stretching, Aerobic & Strength Training Stretching, Aerobic & Strength Training Strength Training
Supervised
DeFor et al., 2007
Aerobic
Combination
Dimeo et al., 1996
Aerobic
Supervised
Coleman et al., 2008
Unsupervised
Dimeo et al., 1997a
Aerobic
Supervised
Dimeo et al., 1997b
Aerobic
Supervised
Hacker et al., 2011a
Strength Training
Combination
Hacker et al., 2011b Hayes et al., 2003, 2004a, 2004b Inoue et al., 2010 Jarden et al., 2009 Kim and Kim, 2006 Knols et al., 2011 Mello et al., 2003 Shelton et al., 2009 Wilson et al., 2005 Wiskemann et al., 2011 Totals
Strength Training Aerobic and Strength Training Aerobic and Strength Training Aerobic and Strength Training Strength training Aerobic and Strength Training Aerobic and Strength Training Aerobic and Strength Training Aerobic Aerobic and Strength Training
Combination Supervised Supervised Unsupervised Supervised Combination Supervised Supervised Unsupervised Combination
N ¼ 998
Number (%) completers
Design
Timing of intervention
49 (77%)
RCTb
Acute recovery
12 (100%)
QEc
Long-term recovery
13(54%)
RCT
Acute recovery
120(89%)
RCT
Acute recovery
30(75%)
RCT
Acute recovery
14(70%)
QE
Acute recovery
64(91%)
RCT
Acute recovery
32(89%)
QE
Acute recovery
17(90%)
RCT
Acute recovery
10(100%)
QE
Acute recovery
12(100%)
QE
Acute recovery
26(100%)
QE
Acute recovery
34(81%)
RCT
Acute recovery
35(83%)
RCT
Acute recovery
105(80%)
RCT
Acute recovery
18(56%)
RCT
Acute recovery
53(87%)
RCT
Acute recovery
13(77%)
QE
80(76%)
RCT
Acute and long-term recovery Acute recovery
autologous
81(81%)
autologous
autologous autologous
autologous
autologous
818(82%)
Note: Acute recovery denotes within the first year following bone marrow or hematopoietic stem cell transplantation. Long-term recovery denotes more than one year post bone marrow or hematopoietic stem cell transplantation. a Sample size indicates number enrolled. The number of subjects that complete the program may be different. b RCT: randomized controlled trial. c QE: quasi-experimental.
(n ¼ 7; 35%). The aerobic exercise interventions varied and included activities such as stationary bicycling, walking, or treadmill walking. Other exercise modalities tested included: (1) ¼ strength training (n ¼ 4; 20%) or, (2) combination of stretching, aerobic and strength training (n ¼ 2; 10%). The strength training interventions used elastic bands for resistance and weights. The amount of supervision required to implement the exercise intervention was examined to determine how much labor was involved in implementing the intervention. Supervised exercise sessions (55%; n ¼ 11) were most common while unsupervised sessions least common (20%; n ¼ 4). Five studies (25%) used a combination approach by supervising some sessions with study participants completing other sessions unsupervised. Subject attrition Overall, the 20 studies enrolled 998 subjects and retained 818 subjects (82%). The mean sample size at enrollment across all studies was 49.9 (SD ¼ 39.38) with an average of 40.9 (SD ¼ 33.05) completing research activities. There was a wide variation in sample sizes, however, with initial sample sizes ranging from 10 to 135 subjects and the number of subjects completing study
activities ranging from 10 to 120 subjects (Fig. 2). The patient attrition rate for the exercise intervention studies ranged from 0% to 44%. Few studies retained 100% of the enrolled subjects (n ¼ 4 studies) and these studies enrolled 26 participants each. Three of the four studies were supervised with two conducted in the acute recovery phase (less than a year post transplant) and the other in long-term survivors (more than a year post transplant). Seven (35%) of the exercise intervention studies retained less than 80% of their original sample subjects with nine studies (45%) retaining 80e92%. The reasons for subject attrition cited in the studies were examined, summarized, and rank-ordered (Table 2). A total of 180 subjects withdrew from the 20 studies. Five major categories for subject attrition were identified. These included: (1) death; (2) change in subject’s health status; (3) issues related to the research protocol; (4) personal issues with subjects; and, (5) no reason provided. The most common reason for subject attrition in the exercise intervention studies was death with 79 subjects (44% of subject attrition) expiring during the course of the study. Importantly, the causes of the death in these subjects were not attributed to the exercise intervention. Another 44 subjects (24% of subject
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Fig. 2. Subject attrition in exercise intervention studies following BMT/SCT.
attrition) were either removed from the studies or chose to leave the studies after a change in their health condition, such as disease progression or disease recurrence. Protocol issues, such as inability to collect data at specified time points or cancer chemotherapy treatment not being received, were cited as the reason for attrition in 21 subjects (12%) while another 14% (n ¼ 23 subjects) did not provide a reason. Finally, 5 subjects (3%) withdrew from the studies citing personal issues, such as being too busy. It is important to note that not all subjects who chose to discontinue participation or were removed from the studies were assigned to the exercise group. Forty eight percent of the subjects were assigned to the exercise arm (n ¼ 87) while 36% (n ¼ 64) were assigned to the control arm (Table 2). The treatment allocation for the remaining subjects who did not complete research activities was not specified (16%). Adherence to exercise interventions Methods to measure adherence to the exercise intervention as well as rates of adherence were examined broadly in the 20 studies (Table 3). In studies employing a supervised approach, adherence to the exercise interventions can be readily evaluated by determining the number of exercise sessions completed or the percentage of the exercise prescription completed. In the 11 studies that employed a supervised exercise program, more than two-thirds (n ¼ 8; 73%) did not report adherence rates. Two supervised studies reported adherence rate as mean attendance at exercise sessions (75% and 90%). One study reported an adherence measure (attendance) but did not report the adherence rate. Five studies combined a supervised approach with an unsupervised exercise component. Four of the five studies reported adherence rates while one did not. Three studies reported adherence as the ability to successfully execute the prescribed exercise (range, 50e100% exercise adherence) while one study reported that 24% of subjects followed the suggested routine (prescribed exercise intervention) 100% of the time.
All of the unsupervised exercise intervention studies (n ¼ 4) relied on patient self-report in the form of logs or diaries to document adherence to the exercise program. Even though the methods to measure adherence were reported, the actual adherence rates were only reported in one unsupervised study. This study reported a mean adherence rate of 75% over the six month duration of the study. Discussion The ever-expanding literature base investigating links between exercise and cancer reflects the substantial interest in the role that exercise may play in reducing the incidence of cancer, cancer recurrence, and cancer- or cancer treatment-related side effects. The first article evaluating an exercise intervention following BMT was published in 1986 (Cunningham et al., 1986). By December 2012, researchers had implemented exercise interventions in a variety of cancer populations across the cancer trajectory, including those receiving high dose chemotherapy followed by BMT or SCT. It is no longer a question of whether exercise is beneficial, as the research base supports the use of exercise for achieving a wide spectrum of health-related outcomes (Mishra et al., 2012a, 2012b). Researchers now ask more sophisticated questions, such as what is the most appropriate exercise prescription for achieving healthrelated outcomes in people with cancer; what type of exercise (aerobic, strength training, stretching, or a combination) is most appropriate to implement across a variety of settings; and what is the most efficient doseeresponse? Importantly, questions regarding subject attrition and adherence to exercise interventions must be addressed to identify those interventions that are likely to be successful when translated into clinical practice. Implementing an exercise study in people who have received high dose chemotherapy followed by BMT or SCT presents unique challenges that impact subject retention as well as adherence to the exercise intervention. Exercise studies can be very expensive to
E.D. Hacker, M. Mjukian / European Journal of Oncology Nursing 18 (2014) 175e182 Table 2 Cited reasons for subject attrition. Reason and number of subjects
Treatment allocation
Death (not related to exercise study) (n¼79)
Ex ¼ 33 C ¼ 33 NS ¼ 13
Change in subject’s health status (n¼44) Medical complications Disease progression Chemotherapy induced cardiomyopathy Comorbid other than cancer Developed Complications Progressive Disease Recurrence of active disease Avascular necrosis
EX ¼ 26 C ¼ 14 NS ¼ 4
Protocol issues (n ¼ 21) Withdrew from multiple myeloma treatment protocol Refused to continue participation Did not complete the study Dropped out prior to allogeneic SCT Refused to continue with treatment assignment Did not agree to allocation Refused before completing post test
EX ¼ 7 C ¼ 10 NS ¼ 4
Personal issues (n ¼ 13) Busy with work Lost interest Moved away Refused before completing the post test
EX ¼ 4 C¼1
Reasons not provided (n ¼ 23) Left study before 2nd data collection point (reason not reported) Left study before 3rd data collection point (reason not reported) Dropped Out Withdrew from study
EX ¼ 17 C¼6
Miscellaneous (n ¼ 8) Reason for attrition not assigned as exact number of subjects per reason not specified. Subjects dropped for personal and medical reasons.
NS ¼ 8
EX e Exercise group; C e Control group; NS e Not Specified.
implement, especially if specialized equipment (such as treadmills or metabolic carts) is needed and/or if supervision is required for testing subjects’ performance status and/or to implement the exercise intervention. Subject attrition is always a concern for researchers and should be particularly concerning to researchers interested in testing an exercise intervention. This paper provides an attempt to quantify subject attrition and to determine the reasons for subject attrition in exercise studies involving people who have received BMT or SCT. This information is important to help researchers determine whether subject attrition rates in their studies are consistent with studies using similar interventions and populations. This information also provides both researchers and clinicians with the data that they may need to estimate projected sample sizes and address feasibility and acceptability issues, particularly if the research is to be translated into clinical practice. In this review of prospective BMT/SCT exercise intervention studies, subject retention rate was surprisingly high (82%) although there was variation. The high retention rate likely reflects widespread acceptance of exercise as beneficial. For those people who do not like to exercise and/or do not feel that they can readily master the activity, they may refuse participation right from the outset, thus, limiting subject attrition. For those who agree to participate, exercise may be seen as having direct health benefits (especially if assigned to the exercise arm) promoting continued
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participation. In addition, subjects may perceive exercise as an achievable health behavior that is within their control, contributing to their willingness to continue participation (Courneya et al., 2005). High retention rates in the BMT/SCT exercise studies may also reflect the researchers’ ability to tailor the exercise interventions appropriately to this unique population. For instance, conducting the exercise program during regularly scheduled clinic appointments is an opportune time for subjects to exercise under supervision while reducing subject burden associated with additional research visits. We have found this approach to be well received among hematopoietic stem cell transplant patients (Hacker et al., 2011a). The importance of providing reasons for subject attrition in BMT/SCT exercise studies cannot be overestimated. When reasons for subject attrition are not provided, readers are essentially left to their own devices for conjuring up a reason. Was the exercise intervention too difficult for the subjects? Was the subject burden too much if subjects were required to attend a set number of supervised exercise sessions per week? Were the subjects too ill to participate in the exercise program? These questions can be simply answered just by including subject attrition information in the published report. In this review, death was the most common reason for subject attrition. The number of deaths in the exercise arm was approximately the same as the control arm. Importantly, the exercise intervention did not lead to death in any of the subjects assigned to the exercise arm. Not surprisingly, a change in the subject’s health status was the second most common reason for subject attrition in the BMT/SCT exercise intervention studies. This supports the notion that implementing an exercise program in people following BMT or SCT is challenging as disease progression or ability to tolerate therapy cannot always be predicted. For example, this review identified disease recurrence, disease progression, chemotherapyinduced cardiomyopathy, and avascular necrosis as a few examples of changes in health status that resulted in subject attrition. Unfortunately, researchers are unable to predict with complete accuracy those who will develop complications or expire prior to enrollment. Establishing appropriate inclusion criteria for an exercise study following BMT/SCT helps to increase the likelihood of subject retention, although not in all cases. Losing subjects to changes in health status may be more problematic in studies that involve people in the first year following BMT/HSCT compared to long-term survivors as changes in health status tend to occur frequently in the first year post transplant (Pidala et al., 2009). In this review, the majority of exercise intervention studies were conducted in the acute recovery period (during the first year post BMT or SCT). Unfortunately, implementing an exercise intervention may prove difficult during the acute recovery phase, even if the exercise intervention is only mildly intense. On the other hand, waiting until all therapy is completed prior to initiating an exercise program may lead to even more physical deconditioning following BMT/SCT, especially for those who lived a sedentary life prior to the intensive therapy. One solution to mitigate the problem with subject attrition due to changing health status is to tailor the exercise interventions to the individual’s capacity with frequent periods of reassessment. This is an area of inquiry that is ripe for research and will help determine the appropriate time to implement an exercise intervention to enhance health-related outcomes and decrease the potential for subject attrition in exercise studies. Conducting clinical research requires flexibility to adapt to dynamic situations. Implementing an exercise intervention in a dynamic clinical environment is bound to result in protocol implementation issues that also impact subject attrition. This review identifies some of the methodological issues associated with subject attrition in BMT or HSCT exercise studies, such as inability to
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Table 3 Adherence to exercise interventions. Study
Amount of supervision
Adherence to exercise intervention reported
Baumann et al., 2010 Carlson et al., 2006 Coleman et al., 2003
Supervised Supervised Unsupervised
No Yes Yes
Coleman et al., 2008
Unsupervised
Yes
Cunningham et al., 1986 DeFor et al., 2007
Supervised Combination
No Yes
Dimeo et al., 1996 Dimeo et al., 1997a Dimeo et al., 1997b Hacker et al., 2011a
Supervised Supervised Supervised Combination
No No No Yes
Hacker et al., 2011b
Combination
Yes
Hayes et al., 2003, 2004a, 2004b Inoue et al., 2010 Jarden et al., 2009 Kim and Kim, 2006 Knols et al., 2011 Mello et al., 2003 Shelton et al., 2009
Supervised
Yes
Supervised Unsupervised Supervised Combination Supervised Supervised
No Yes No No No Yes
Wilson et al., 2005 Wiskemann et al., 2011
Unsupervised Combination
Yes Yes
complete pre- and post-testing sessions or failure to agree to treatment allocations. Failure to agree to treatment allocation and/ or diffusion of treatment effect (subjects in the control arm engaging in exercise behaviors) may be particularly troublesome in BMT or SCT studies given the widespread acceptance of the benefits of exercise. Furthermore, it would be considered unethical to tell a subject assigned to the control arm not to exercise. Several solutions to this problem may be helpful such as wait listing the exercise component or comparing exercise modalities with different mechanisms of action. Regardless of the solution, it is critical to ask about exercise behaviors in subjects in the control arm. For example, in our pilot randomized controlled trial, two of the nine subjects assigned to the usual activity arm exercised although they did not begin exercising until four weeks later than the exercise arm (Hacker et al., 2011a). Very few subjects withdrew from the BMT/HSCT because of personal issues, such as too busy with work. This suggests that subjects, in general, are able to realistically determine whether or not they have adequate resources at their disposal to participate and investigators have provided subjects with realistic information regarding burden of participating in an exercise intervention study. While subject attrition rates provide readers with specifics regarding subjects who fail to complete research activities, information regarding adherence to the exercise program is also needed. For instance, researchers and clinicians need to know how much exercise is needed to sustain a specified effect. What exercise prescription yields the most benefit and results in the greatest adherence? What
Methods to enhance and/or monitor exercise adherence
Adherence rates
Completion of exercise sessions. Self-report of exercise with weekly review of exercise logs.
90% On average, the exercise group completed the six-month exercise prescription 75% of the time
Self-report in exercise logs with periodic personal interviews to enhance compliance. Self-report in exercise log or diary.
10(24%) followed the suggested routine 100% of the time
Self-report using exercise logs for unsupervised visits. Completion of exercise sessions for supervised visits
Exercising 3 times per week ranged from 50 to 100% over the six week intervention. Exercising 1e2 times per week ranged from 0 to 38% over the six week intention. Only one patient did not exercise in one week. By Week 6, 60% exercising 3 times per week, 20% exercising 1e2 times per week
Self-report using exercise logs for unsupervised visits. Completion of exercise sessions for supervised visits Attendance at exercise sessions
Self-report in exercise logs
Completion of exercise sessions. Self-report diary Self-report in exercise logs
Subjects completed an average of 9 out 12 exercise sessions 87.5% before HSCT, 83% during inpatient hospitalization, and 91.3% 6e8 weeks following hospital discharge.
is considered to be an acceptable adherence rate? Should the same standard for adherence rates exist for supervised versus unsupervised programs? High-intensity compared to mild-intensity? This review suggests that researchers frequently neglect to publish adherence rates to supervised exercise interventions, as more than two-thirds of the supervised exercise intervention studies did not report this information. The reasons for this are unclear. Perhaps there is an assumption that unpublished adherence data reflect 100% completion of all exercise activities. Given the ease to collect adherence to exercise interventions, particularly in supervised exercise intervention studies, it is essential to address this issue in publication so that clinicians and researchers can determine the likelihood of successful implementation of the exercise intervention in their BMT or SCT populations. Researchers that employ an unsupervised or a combination approach to an exercise study may find it more difficult to collect adherence data, particularly if relying only on self-report information. Problems associated with self-report diaries have been documented elsewhere, and there is little reason to believe that these problems would be different for an exercise intervention study involving BMT or SCT patients (Stone et al., 2002). For instance, forgetting to document an exercise session and/or documenting all the sessions in one sitting are just two of the many potential problems when using self-reporting mechanisms. In this review of the literature, all unsupervised exercise intervention studies relied on self-report to examine adherence to the exercise intervention. Supplementing subjective data (self-report) with
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objective data (such as pedometers or accelerometers) may provide additional information related to the fidelity of the intervention, however, most objective devices, such as accelerometers, are not able to specifically pinpoint the type of exercise being conducted, only the increase in physical activity. Even so, adherence data are particularly important, as they provide doseeresponse exercise information. In this review, adherence to the exercise prescription ranged from 50% to 100%, illustrating the wide variation for adhering to exercise interventions and the importance for noting this information to evaluate dose-responsiveness. Conclusions Exercise research following BMT or SCT is becoming more sophisticated as researchers build upon the expanding literature base. In general, subject attrition from exercise studies involving BMT or SCT patients is relatively low, although there is wide variation. The reasons for subject attrition include death, changes in health status, issues related to the research protocol, personal issues with subjects, and loss to follow-up or no reason provided. Even though death was the single largest cited reason for subject attrition in this review, none of the deaths were the result or related to the exercise intervention. Little information regarding adherence to supervised exercise interventions following BMT or SCT is provided in the literature, even though this information is relatively easy to collect especially for supervised exercise interventions. Collecting adherence data in unsupervised exercise studies may be more difficult, given the potential problems with self-report data. Future studies may consider adding an objective measure of physical activity, such as pedometers or accelerometers to supplement this self-reported adherence data. Conflict of interest statement None declared. References Adamsen, L., Quist, M., Andersen, C., Moller, T., Herrstedt, J., Kronborg, D., et al., 2009. Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial. British Medical Journal 339, b3410. Arikawa, A.Y., O’Dougherty, M., Kaufman, B.C., Schmitz, K.H., Kurzer, M.S., 2012. Attrition and adherence of young women to aerobic exercise: lessons from the WISER study. Contemporary Clinical Trials 33 (2), 298e301. http://dx.doi.org/ 10.1016/j.cct.2011.11.017. Baumann, F.T., Kraut, L., Schule, K., Bloch, W., Fauser, A.A., 2010. A controlled randomized study examining the effects of exercise therapy on patients undergoing haematopoietic stem cell transplantation. Bone Marrow Transplantation 45 (2), 355e362. http://dx.doi.org/10.1038/bmt.2009.163. Brown, J.C., Huedo-Medina, T.B., Pescatello, L.S., Pescatello, S.M., Ferrer, R.A., Johnson, B.T., 2011. Efficacy of exercise interventions in modulating cancerrelated fatigue among adult cancer survivors: a meta-analysis. Cancer Epidemiology, Biomarkers & Prevention 20 (1), 123e133. http://dx.doi.org/10.1158/ 1055-9965.EPI-10-0988. Carlson, L.E., Smith, D., Russell, J., Fibich, C., Whittaker, T., 2006. Individualized exercise program for the treatment of severe fatigue in patients after allogeneic hematopoietic stem-cell transplant: a pilot study. Bone Marrow Transplantation 37 (10), 945e954. Carlson, S.A., Fulton, J.E., Schoenborn, C.A., Loustalot, F., 2010. Trend and prevalence estimates based on the 2008 Physical Activity Guidelines for Americans. American Journal of Preventative Medicine 39 (4), 305e313. http://dx.doi.org/ 10.1016/j.amepre.2010.06.006. Coleman, E.A., Coon, S., Hall-Barrow, J., Richards, K., Gaylor, D., Stewart, B., 2003. Feasibility of exercise during treatment for multiple myeloma. Cancer Nursing 26 (5), 410e419. Coleman, E.A., Coon, S.K., Kennedy, R.L., Lockhart, K.D., Stewart, C.B., Anaissie, E.J., et al., 2008. Effects of exercise in combination with epoetin alfa during highdose chemotherapy and autologous peripheral blood stem cell transplantation for multiple myeloma. Oncology Nursing Forum 35 (3), E53eE61. Courneya, K.S., Friedenreich, C.M., Quinney, H.A., Fields, A.L., Jones, L.W., Fairey, A.S., 2004. Predictors of adherence and contamination in a randomized trial of exercise in colorectal cancer survivors. Psychooncology 13 (12), 857e866.
181
Courneya, K.S., Friedenreich, C.M., Quinney, H.A., Fields, A.L., Jones, L.W., Vallance, J.K., et al., 2005. A longitudinal study of exercise barriers in colorectal cancer survivors participating in a randomized controlled trial. Annals of Behavioral Medicine 29 (2), 147e153. Courneya, K.S., Karvinen, K.H., McNeely, M.L., Campbell, K.L., Brar, S., Woolcott, C.G., et al., 2012. Predictors of adherence to supervised and unsupervised exercise in the Alberta Physical Activity and Breast Cancer Prevention Trial. Journal of Physical Acivity & Health 9 (6), 857e866. Courneya, K.S., Sellar, C.M., Stevinson, C., McNeely, M.L., Peddle, C.J., Friedenreich, C.M., et al., 2009. Randomized controlled trial of the effects of aerobic exercise on physical functioning and quality of life in lymphoma patients. Journal of Clinical Oncology 27 (27), 4605e4612. http://dx.doi.org/ 10.1200/JCO.2008.20.0634. Cramp, F., Byron-Daniel, J., 2012. Exercise for the management of cancer-related fatigue in adults. Cochrane Database of Systematic Reviews 11, CD006145. http://dx.doi.org/10.1002/14651858.CD006145.pub3. Cunningham, B.A., Morris, G., Cheney, C.L., Buergel, N., Aker, S.N., Lenssen, P., 1986. Effects of resistive exercise on skeletal muscle in marrow transplant recipients receiving total parenteral nutrition. Journal of Parenteral and Enteral Nutrition 10 (6), 558e563. DeFor, T.E., Burns, L.J., Gold, E.M., Weisdorf, D.J., 2007. A randomized trial of the effect of a walking regimen on the functional status of 100 adult allogeneic donor hematopoietic cell transplant patients. Biology of Blood and Marrow Transplantation 13 (8), 948e955. Dimeo, F., Bertz, H., Finke, J., Fetscher, S., Mertelsmann, R., Keul, J., 1996. An aerobic exercise program for patients with haematological malignancies after bone marrow transplantation. Bone Marrow Transplantation 18 (6), 1157e1160. Dimeo, F., Fetscher, S., Lange, W., Mertelsmann, R., Keul, J., 1997a. Effects of aerobic exercise on the physical performance and incidence of treatment-related complications after high-dose chemotherapy. Blood 90 (9), 3390e3394. Dimeo, F., Tilmann, M.H.N., Bertz, H., Kanz, L., Mertelsmann, R., Keul, J., 1997b. Aerobic exercise in the rehabilitation of cancer patients after high dose chemotherapy and autologous peripheral stem cell transplantation. Cancer 79, 1717e1722. Hacker, E.D., Larson, J., Kujath, A., Peace, D., Rondelli, D., Gaston, L., 2011a. Strength training following hematopoietic stem cell transplantation. Cancer Nursing 34 (3), 238e249. Hacker, E.D., Larson, J.L., Peace, D., 2011b. Exercise in patients receiving hematopoietic stem cell transplantation: lessons learned and results from a feasibility study. Oncology Nursing Forum 38 (2), 216e223. Hayes, S., Davies, P.S., Parker, T., Bashford, J., 2003. Total energy expenditure and body composition changes following peripheral blood stem cell transplantation and participation in an exercise programme. Bone Marrow Transplantation 31 (5), 331e338. Hayes, S.C., Davies, P.S., Parker, T.W., Bashford, J., Green, A., 2004a. Role of a mixed type, moderate intensity exercise programme after peripheral blood stem cell transplantation. British Journal of Sports Medicine 38 (3), 304e309 discussion 309. Hayes, S., Davies, P.S., Parker, T., Bashford, J., Newman, B., 2004b. Quality of life changes following peripheral blood stem cell transplantation and participation in a mixed-type, moderate-intensity, exercise program. Bone Marrow Transplantation 33 (5), 553e558. Inoue, J., Ono, R., Okamura, A., Matsui, T., Takekoshi, H., Miwa, M., et al., 2010. The impact of early rehabilitation on the duration of hospitalization in patients after allogeneic hematopoietic stem cell transplantation. Transplantation Proceedings 42 (7), 2740e2744. http://dx.doi.org/10.1016/ j.transproceed.2010.05.153. Jarden, M., Baadsgaard, M.T., Hovgaard, D.J., Boesen, E., Adamsen, L., 2009. A randomized trial on the effect of a multimodal intervention on physical capacity, functional performance and quality of life in adult patients undergoing allogeneic SCT. Bone Marrow Transplantation 43 (9), 725e737. Kim, S.D., Kim, H.S., 2006. A series of bed exercises to improve lymphocyte count in allogeneic bone marrow transplantation patients. European Journal of Cancer Care (Engl) 15 (5), 453e457. Knols, R.H., de Bruin, E.D., Uebelhart, D., Aufdemkampe, G., Schanz, U., StennerLiewen, F., et al., 2011. Effects of an outpatient physical exercise program on hematopoietic stem-cell transplantation recipients: a randomized clinical trial. Bone Marrow Transplantation 46 (9), 1245e1255. Mello, M., Tanaka, C., Dulley, F.L., 2003. Effects of an exercise program on muscle performance in patients undergoing allogeneic bone marrow transplantation. Bone Marrow Transplantation 32 (7), 723e728. Midtgaard, J., Rorth, M., Stelter, R., Tveteras, A., Andersen, C., Quist, M., et al., 2005. The impact of a multidimensional exercise program on self-reported anxiety and depression in cancer patients undergoing chemotherapy: a phase II study. Palliative & Supportive Care 3 (3), 197e208. Mishra, S.I., Scherer, R.W., Geigle, P.M., Berlanstein, D.R., Topaloglu, O., Gotay, C.C., et al., 2012a. Exercise interventions on health-related quality of life for cancer survivors. Cochrane Database of Systematic Reviews 8, CD007566. http:// dx.doi.org/10.1002/14651858.CD007566.pub2. Mishra, S.I., Scherer, R.W., Snyder, C., Geigle, P.M., Berlanstein, D.R., Topaloglu, O., 2012b. Exercise interventions on health-related quality of life for people with cancer during active treatment. Cochrane Database of Systematic Reviews 8, CD008465. http://dx.doi.org/10.1002/14651858.CD008465.pub2.
182
E.D. Hacker, M. Mjukian / European Journal of Oncology Nursing 18 (2014) 175e182
Pidala, J., Anasetti, C., Jim, H., 2009. Quality of life after allogeneic hematopoietic cell transplantation. Blood 114 (1), 7e19. Schwartz, A.L., Mori, M., Gao, R., Nail, L.M., King, M.E., 2001. Exercise reduces daily fatigue in women with breast cancer receiving chemotherapy. Medicine & Science in Sports & Exercise 33 (5), 718e723. Shelton, M.L., Lee, J.Q., Morris, G.S., Massey, P.R., Kendall, D.G., Munsell, M.F., et al., 2009. A randomized control trial of a supervised versus a self-directed exercise program for allogeneic stem cell transplant patients. Psychooncology 18 (4), 353e359. Speck, R.M., Courneya, K.S., Masse, L.C., Duval, S., Schmitz, K.H., 2010. An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. Journal of Cancer Survivorship 4 (2), 87e100. http://dx.doi.org/ 10.1007/s11764-009-0110-5. Stone, A.A., Shiffman, S., Schwartz, J.E., Broderick, J.E., Hufford, M.R., 2002. Patient non-compliance with paper diaries. British Medical Journal 324 (7347), 1193e 1194.
Wilson, R.W., Jacobsen, P.B., Fields, K.K., 2005. Pilot study of a home-based aerobic exercise program for sedentary cancer survivors treated with hematopoietic stem cell transplantation. Bone Marrow Transplantation 35 (7), 721e727. Wiskemann, J., Dreger, P., Schwerdtfeger, R., Bondong, A., Huber, G., Kleindienst, N., et al., 2011. Effects of a partly self-administered exercise program before, during, and after allogeneic stem cell transplantation. Blood 117 (9), 2604e2613. Wiskemann, J., Huber, G., 2008. Physical exercise as adjuvant therapy for patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplantation 41 (4), 321e329. Yeo, T.P., Burrell, S.A., Sauter, P.K., Kennedy, E.P., Lavu, H., Leiby, B.E., et al., 2012. A progressive postresection walking program significantly improves fatigue and health-related quality of life in pancreas and periampullary cancer patients. The Journal of the American College of Surgeons 214 (4), 463e475. http:// dx.doi.org/10.1016/j.jamcollsurg.2011.12.017 discussion 475-467.
