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PHYS THER
Vol. 82, No. 7, July 2002, pp. 716-721

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Evidence In Practice

Does exercise during hospitalization after stem cell transplantation decrease reports of fatigue and reduce the duration of the hospital stay?

David A Scalzitti and Cynthia Sternisha

David A Scalzitti, PT, MS, OCS, is Clinical Instructor, Department of Physical Therapy, University of Illinois at Chicago, Chicago, Ill, and Specialist in Physical Therapy, Department of Physical Therapy, University of Illinois Hospital, Chicago, Ill
Cynthia Sternisha, PT, is Center Coordinator of Clinical Education, Department of Physical Therapy, University of Illinois Hospital


A 46-year-old woman was admitted to our facility with the diagnosis of multiple myeloma. At the time of admission, she did not report pain, fever, nausea, vomiting, or fatigue. Her body temperature was 37.1°C (98.7°F), her heart rate was 66 beats per minute, her respiratory rate was 18 breaths per minute, and her blood pressure was 117/77 mm Hg. Laboratory values included a platelet count of 668,000/mL, a white blood cell count of 7,000/mL, and hemoglobin of 10.0 g/dL. Before the diagnosis of multiple myeloma, she had worked full-time as a day care worker and reported that she was functionally independent at the time of this admission. After admission, she received high-dose chemotherapy for 2 days before undergoing autologous peripheral stem cell transplantation on the third day.

Three days following the stem cell transplantation, her temperature was 37.7°C (99.8°F), her heart rate was 80 beats per minute, her respiratory rate was 16 breaths per minute, and her blood pressure was 120/72 mm Hg. Her platelet count decreased to 422,000/mL, her white blood cell count deceased to 2,700/mL, and her hemoglobin decreased to 9.3 g/dL. She reported feeling weak and tired, and she had difficulty eating because she always felt nauseous. The patient used the bedside commode frequently because of diarrhea. She walked to the bathroom once a day to take a seated shower according to the attending physician's orders for physical activity.

Typically, the medical team at our facility requests a physical therapy consultation only when the patient is unable to perform basic activities of daily living. In this case, however, the attending physician contacted the physical therapy department for information on the benefits and risks of exercise after stem cell transplantation. He was concerned that an increase in physical activity might exacerbate the patient's symptoms and might lead to cardiotoxicity because of a suppressed immune system following the high-dose chemotherapy. In our experience, exercise has allowed patients who were unable to perform activities of daily living to become functionally independent for discharge. Because we were not familiar with the current evidence for the benefits and risks of exercise after stem cell transplantation, we decided to search the literature.


    Database used for search: MEDLINE
 
MEDLINE, a service of the National Library of Medicine, contains over 11 million citations from over 4,600 biomedical journals that date back to the mid-1960s. We selected this database because we wanted to access literature that included studies of the use of exercise in people with our patient's medical condition. We also wanted to use the Clinical Queries feature (www.ncbi.nlm.nih.gov/entrez/query/static/clinical.html) within PubMed (the free, public, online version of MEDLINE) to help focus the search. We accessed PubMed via the Internet at www.ncbi.nlm.nih.gov/PubMed, and the Clinical Queries service was accessed by clicking on the Clinical Queries link at the left side of the PubMed search screen. This search was performed on February 18, 2002.


    Strategy: Clinical Queries
 Top
 Database used for search:...
 Strategy: Clinical Queries
 Keywords: exercise AND (stem...
 Selection of articles for...
 Clinical decision:
 References
 
According to the documentation contained in PubMed's Help feature (accessed through the link on the left side of the PubMed search screen), the Clinical Queries feature uses filters to focus a literature search on studies that are more relevant to clinical practice. The filters use search strategies that are based on the findings of Haynes RB et al.1

The Clinical Queries feature allows the user to set 2 filters to focus the search. The first filter requires the user to select 1 of 4 study categories: Therapy, Diagnosis, Etiology, or Prognosis. The second filter requires the user to select 1 of 2 types of emphasis: Sensitivity or Specificity. According to the Clinical Queries search screen, the sensitivity emphasis will yield more references than the specificity emphasis, but some references will be less relevant than other references. In contrast, an emphasis on specificity will yield references specific to the search terms but may exclude some appropriate references.

We chose to filter for articles according to Therapy and Sensitivity. The therapy category focuses the search on studies with content pertinent to treatment or prevention. In conjunction with the therapy category, the sensitivity emphasis targets studies that are classified according to the publication type "Randomized Controlled Trials" or indexed according to the MEDLINE subject heading "Therapeutic Use." In contrast, the specificity emphasis in conjunction with the therapy category will select studies that include the text words "double blind" or "placebo." Because our clinical question relates to exercise, we hypothesized that we were more likely to find studies of the randomized controlled trial type than double blind studies.


    Keywords: exercise AND (stem cell transplantation OR bone marrow transplantation) AND human
 Top
 Database used for search:...
 Strategy: Clinical Queries
 Keywords: exercise AND (stem...
 Selection of articles for...
 Clinical decision:
 References
 
For the subject search, we chose to use keywords that combined the intervention with the condition. For the intervention we used the keyword exercise, because it is more general and would include other specific types of exercise (eg, aerobic exercise). For the condition we decided to search on stem cell transplantation OR bone marrow transplantation. We used this combination of keywords because the clinical effects on function and the physiological effects following either stem cell or bone marrow transplantation are similar. We used the conjunction OR in order to include studies that included either of these terms. If we had chosen to use the conjunction AND to combine the terms, the search would have been limited to only those studies that were indexed using both terms. We decided against including the medical diagnosis (multiple myeloma) in the search because we were interested in studies that investigated the effect of exercise following medical management of the condition and not on the condition itself. Finally, the keyword human was added to limit the search to studies that had investigated human populations and to exclude animal studies. Parentheses were used to order PubMed to process the search terms inside the parentheses first and then combine these results with the search terms outside the parentheses. The Boolean operators "AND" and "OR" were capitalized according to PubMed's search rules.
Citations Retrieved by Clinical Queries Search Filtered for Therapy and Sensitivity Using the Keywords "Exercise," "Stem Cell Transplantation," "Bone Marrow Transplantation," and "Human"

  1. Courneya KS, Keats MR, Turner AR. Physical exercise and quality of life in cancer patients following high dose chemotherapy and autologous bone marrow transplantation. Psychooncology. 2000 Mar-Apr;9(2):127-36.
  2. Dimeo FC, Stieglitz RD, Novelli-Fischer U, Fetscher S, Keul J. Effects of physical activity on the fatigue and psychologic status of cancer patients during chemotherapy. Cancer. 1999 May 15;85(10):2273-7.
  3. Dimeo F, Fetscher S, Lange W, Mertelsmann R, Keul J. Effects of aerobic exercise on the physical performance and incidence of treatment-related complications after high-dose chemotherapy. Blood. 1997 Nov 1;90(9):3390-4.
  4. Dimeo FC, Tilmann MH, Bertz H, Kanz L, Mertelsmann R, Keul J. Aerobic exercise in the rehabilitation of cancer patients after high dose chemotherapy and autologous peripheral stem cell transplantation. Cancer. 1997 May 1;79(9):1717-22.
  5. Jain B, Floreani AA, Anderson JR, Vose JM, Robbins RA, Rennard SI, Sisson JH. Cardiopulmonary function and autologous bone marrow transplantation: results and predictive value for respiratory failure and mortality. The University of Nebraska Medical Center Bone Marrow Transplantation Pulmonary Study Group. Bone Marrow Transplant. 1996 Apr;17(4):561-8.
  6. Hertenstein B, Stefanic M, Schmeiser T, Scholz M, Goller V, Clausen M, Bunjes D, Wiesneth M, Novotny J, Kochs M. Cardiac toxicity of bone marrow transplantation: predictive value of cardiologic evaluation before transplant. J Clin Oncol. 1994 May;12(5):998-1004.
  7. Cunningham BA, Morris G, Cheney CL, Buergel N, Aker SN, Lenssen P. Effects of resistive exercise on skeletal muscle in marrow transplant recipients receiving total parenteral nutrition. JPEN J Parenter Enteral Nutr. 1986 Nov-Dec;10(6):558-63.
  8. Baello EB, Ensberg ME, Ferguson DW, Kugler JW, Gingrich RD, Armitage JO, Klassen LW, Kirchner PT, Kerber RE, Marcus ML, et al. Effect of high-dose cyclophosphamide and total-body irradiation on left ventricular function in adult patients with leukemia undergoing allogeneic bone marrow transplantation. Cancer Treat Rep. 1986 Oct;70(10):1187-93.

 

After entering the search terms in the query box at the bottom of the search screen, we clicked on Go and obtained a list of 8 references. In contrast, a search conducted on PubMed's main search screen using the same terms but without the Clinical Queries filters would result in 39 articles. Although the 8 references found using the filters in Clinical Queries would have been included in those 39, many of the others were articles that would have been less relevant to the clinical question—review articles, descriptive studies, and studies where exercise was not the primary intervention.


    Selection of articles for review:
 Top
 Database used for search:...
 Strategy: Clinical Queries
 Keywords: exercise AND (stem...
 Selection of articles for...
 Clinical decision:
 References
 
The 8 references obtained from the Clinical Queries search were listed according to the order that they were entered into MEDLINE, with the most recent references listed first. As we read the titles of the studies, we saw that the first 4 appeared to be investigations of exercise programs in people similar to our patient. These 4 studies were all published since 1997 and would be likely to contain the most recent information. Therefore, we decided to read the abstracts of these citations to determine whether the studies could answer our clinical question.

Courneya KS, Keats MR, Turner AR. Physical exercise and quality of life in cancer patients following high dose chemotherapy and autologous bone marrow transplantation. Psychooncology 2000 Mar-Apr;9(2):127-36. Faculty of Physical Education, Van Vliet Center, University of Alberta, Edmonton, AB, Canada.

Preliminary evidence indicates that physical exercise may be an effective strategy for the rehabilitation of cancer patients following high dose chemotherapy (HDC) and bone marrow transplantation (BMT), but the focus of this research has been on physical fitness and medical outcomes. In the present study, we employed a prospective design to examine the relationship between physical exercise and various quality of life (QOL) indices in 25 BMT patients. Participants completed weekly self-administered questionnaires upon being admitted to hospital, and monitored the frequency and duration of their exercise during hospitalization. Statistical analyses indicated that exercise during hospitalization was significantly correlated with almost all QOL indices, including physical well-being, psychological well-being, depression, anxiety and days hospitalized. Moreover, only some of the correlations were attenuated after controlling for relevant demographic and medical variables. It was concluded that physical exercise may be related to QOL in BMT patients, but that experimental research is needed before any definitive conclusions can be drawn.

2000 John Wiley & Sons, Ltd. Reproduced with permission.]

The abstract of this prospective observational study suggested that there might be a relationship between physical exercise and quality of life in people with cancer following chemotherapy and bone marrow transplantation. Based on the abstract, we decided to review the full text of the article to learn more of the details of this study. Full-text of the article was accessed through Wiley Interscience Journals (www.interscience.wiley.com), an online service to which our health science library subscribes.

Participants in the study were 25 people who had been admitted to the Cross Cancer Institute in Edmonton, Alberta, Canada, for treatment of multiple myeloma, breast cancer, non-Hodgkin lymphoma, and Hodgkin lymphoma. Exercise consisted of encouragement by the physicians and nurses for the patients to begin ambulation and to use the cycle ergometers available in the unit as soon after the transplant as possible. While they were hospitalized, each participant kept a log of the type of exercise performed (cycling or walking) and the amount of time spent exercising. The participants averaged 2.21±2.73 minutes of cycling per day (range=0–8.85) and 7.71±8.59 minutes of cycling or walking per day (range=0–32.31). Indexes used in the assessment of quality of life included the Functional Assessment of Cancer Therapy–BMT, Affect Balance Scale, Satisfaction With Life Scale, Center for Epidemiological Studies Depression Scale, and State-Trait Anxiety Inventory. The duration of exercise per day was correlated with the assessment of quality of life at discharge and total days hospitalized using Pearson correlations to assess the relationship between exercise and quality of life. Although the results of this study indicated that exercise during hospitalization correlated with a shorter hospital stay and with most of the quality of life indexes, a causal relationship could not be determined because of the prospective, observational design of the study. In this article, the authors referenced the 3 other studies that we had previously identified as possibilities from our search. Based on this fact, we decided to obtain the full text of these 3 articles. The full text of the 2 articles published in Cancer were also available online through Wiley Interscience Journals. The full text of the article published in Blood was available at no charge from the American Society of Hematology (www.bloodjournal.org).

Dimeo FC, Stieglitz RD, Novelli-Fischer U, Fetscher S, Keul J. Effects of physical activity on the fatigue and psychologic status of cancer patients during chemotherapy. Cancer 1999 May 15;85(10):2273-7. Department of Rehabilitation, Prevention and Sports Medicine, Freiburg University Medical Center, Germany.

BACKGROUND: Fatigue is a common and often severe problem in cancer patients undergoing chemotherapy. The authors postulated that physical activity training can reduce the intensity of fatigue in this group of patients. METHODS: A group of cancer patients receiving high dose chemotherapy followed by autologous peripheral blood stem cell transplantation (training group; n = 27) followed an exercise program during hospitalization. The program was comprised of biking on an ergometer in the supine position following an interval training pattern for 30 minutes daily. Patients in the control group (n = 32) did not train. Psychologic distress was assessed at hospital admission and discharge with the Profile of Mood States and Symptom Check List 90. RESULTS: By the time of hospital discharge, fatigue and somatic complaints had increased significantly in the control group (P for both < 0.01) but not in the training group. Furthermore, by the time of hospital discharge, the training group had a significant improvement in several scores of psychologic distress (obsessive-compulsive traits, fear, interpersonal sensitivity, and phobic anxiety) (P value for all scores < 0.05); this outcome was not observed in the control group. CONCLUSIONS: The current study found that aerobic exercise can reduce fatigue and improve psychologic distress in cancer patients undergoing chemotherapy.

1999 American Cancer Society. Abstract reprinted with permission of Wiley-Liss Inc, a subsidiary of John Wiley & Sons.]

The results of this randomized controlled trial, which used an intention-to-treat analysis, suggested that a daily 30-minute program of cycling with a bed ergometer at an assigned workload reduced treatment-related fatigue and psychological stress at the time of discharge for patients who received chemotherapy and stem cell transplantation. The 30 minutes of cycling consisted of fifteen 1-minute intervals of pedaling followed by a 1-minute rest. Fatigue and psychological stress were assessed using self-report measures of the Profile of Mood Status and the Symptom Check List-90-R. Participants in both the exercise and nontraining groups primarily had diagnoses of breast carcinoma, but the groups also included people with seminoma, sarcoma, small cell lung carcinoma, Hodgkin disease, and non-Hodgkin lymphoma. The various types of chemotherapy that the patients in both groups received were also identified, as well as the complications that they may have developed during the course of hospitalization. We were encouraged that no adverse effects to the exercise were reported, although 2 patients in the exercise group withdrew due to personal reasons after the second training day.

The data presented in this study showed that the self-report measurement of fatigue increased in both groups; however, the change in the exercise group was not as large as the change in the nontraining group, leading to the authors' conclusions regarding the effects of the training. Because this study used only a self-report measure of fatigue, we were interested in reviewing the other studies from the search for other measures of fatigue and for measures of length of stay in the hospital.

Dimeo F, Fetscher S, Lange W, Mertelsmann R, Keul J. Effects of aerobic exercise on the physical performance and incidence of treatment-related complications after high-dose chemotherapy. Blood 1997 Nov 1;90(9):3390-4. Department of Rehabilitation, Prevention and Sports Medicine, Freiburg University Medical Center, Freiburg in Breisgau, Germany.

Loss of physical performance is a universal problem of cancer patients undergoing chemotherapy. We postulated that this impairment can be partially prevented by aerobic exercise. In a randomized study, 33 cancer patients receiving high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (training group, T) performed an exercise program consisting of biking on an ergometer in the supine position after an interval-training pattern for 30 minutes daily during hospitalization. Patients in the control group (C, n = 37) did not train. Maximal physical performance was assessed with a treadmill test by admission and discharge. Physical performance of the two groups was not different on admission. The decrement in performance during hospitalization was 27% greater in the control group than in the training group (P = .05); this resulted in a significantly higher maximal physical performance at discharge in the trained patients (P = .04). Duration of neutropenia (P = .01) and thrombopenia (P = .06), severity of diarrhea (P = .04), severity of pain (P = .01), and duration of hospitalization (P = .03) were reduced in the training group. We conclude that aerobic exercise can be safely carried out immediately after high-dose chemotherapy and can partially prevent loss of physical performance. Based on the potential significance of the observed outcomes, further studies are warranted to confirm our results.

1997 American Society of Hematology. Abstract reprinted with permission of the American Society of Hematology.]

This randomized controlled trial used an exercise protocol similar to that used in the previous study (Dimeo et al, 1999). Patients in this study with a body temperature above 37.5°C (99.5°F) or platelet counts below 10,000/mL were instructed to interrupt training. In this study, the participants performed a maximal treadmill test before starting chemotherapy and blood stem cell transplantation and performed a follow-up test at discharge from the hospital. The decrease in physical performance, as measured by maximal velocity during the treadmill test, was not as large in the exercise group as for the nontraining group. The duration of hospitalization was shorter for the exercise group than for the nontraining group (13.6±2.2 days vs 15.2±3.6 days). The duration of a white blood cell count below 500,000 g/mL was shorter for the exercise group than for the nontraining group (6.6±1.5 days vs 7.6±1.6 days). The duration of a platelet count below 5,000 g/mL was shorter for the exercise group than for the nontraining group (10.9±3.0 days vs 12.4±3.7 days). The authors concluded that exercise appeared to be safe, based on their data, and that none of the 33 people in the exercise group developed any clinical signs of cardiotoxicity during a 2-month follow-up period.

Dimeo FC, Tilmann MH, Bertz H, Kanz L, Mertelsmann R, Keul J. Aerobic exercise in the rehabilitation of cancer patients after high dose chemotherapy and autologous peripheral stem cell transplantation. Cancer 1997 May 1;79(9):1717-22. Department of Rehabilitation, Prevention and Sports Medicine, Freiburg University Medical Center, Germany.

BACKGROUND: Fatigue and loss of physical performance are frequent problems of cancer patients. In a pilot study, the authors evaluated the feasibility and effects of aerobic training in the rehabilitation of cancer patients after completing high dose chemotherapy. METHODS: Sixteen patients participated in a specially designed rehabilitation program for 6 weeks. The patients entered the program, which consisted of walking on a treadmill, shortly after completing treatment. Sixteen patients who did not train served as controls. Physical performance (maximum speed on the treadmill test), cardiac function, and hemoglobin concentration were compared at the time of discharge from the hospital and 7 weeks later. At the second examination, fatigue and limitations in daily activities due to impaired endurance were assessed during personal interviews. RESULTS: At the time of discharge from the hospital, maximum physical performance (training group: 6.2 +/– 1.1 km/hour; controls: 6.2 +/– 1.3 km/hour) and hemoglobin concentration (training group: 10.1 +/– 1.4 g/dL; controls: 10.1 +/– 1.2 g/dL) were similar for both groups. After 7 weeks, improvement in maximum physical performance (training group: 8.3 +/– 1.6 km/hour; controls 7.5 +/– 1.3 km/hour) and hemoglobin concentration (training group: 13 +/– 1 g/dL controls: 12 +/– 1.4 g/dL) were significantly higher for the training group (P < 0.05). By the second examination, no patient in the training group but 4 controls (25%) reported fatigue and limitations in daily activities due to low physical performance. CONCLUSIONS: Aerobic exercise improves the physical performance of cancer patients recovering from high dose chemotherapy. To reduce fatigue, this group of patients should be counseled to increase physical activity rather than rest after treatment.

1997 American Cancer Society. Abstract reprinted with permission of Wiley-Liss Inc, a subsidiary of John Wiley & Sons.]

The authors used a randomized controlled trial to investigate the effect of training after hospitalization in people who received chemotherapy and stem cell transplantation for cancer. Although the finding of improved physical performance and hemoglobin concentration in an outpatient population was interesting and served as a basis for other studies by this group of authors, we decided that this study did not apply to our clinical question.


    Clinical decision:
 Top
 Database used for search:...
 Strategy: Clinical Queries
 Keywords: exercise AND (stem...
 Selection of articles for...
 Clinical decision:
 References
 
Based on the review of the current evidence, we recommended to the attending physician that an exercise program for hospitalized patients following bone marrow or stem cell transplantation could reduce fatigue and shorten hospital stays. In addition, the exercise programs investigated had a buffering effect on decreases in the white blood cell count and the platelet count typically seen after transplantation. The literature primarily has investigated exercise using bed or bicycle ergometers for 30 minutes daily. The results of Dimeo et al suggest that this form of exercise is safe and improves some measurements of physical activity and quality of life. Based on the methods of these studies, we recommended that caution should be used with exercise for patients with a body temperature above 37.5°C (99.5°F) or platelet counts below 10,000/mL following stem cell or bone marrow transplantation.

The measures of fatigue in these studies have primarily been endurance on a treadmill and self-reports of fatigue. Although self-reports of fatigue are a limiting factor during the rehabilitation of patients after treatment for cancer, how these measurements correspond to meaningful, purposeful activities is unknown. Fatigue is a common report of people with cancer following chemotherapy with stem cell transplantation or bone marrow transplantation. These interventions may be used for people with multiple myeloma, lymphoma, Hodgkin disease, leukemia, and breast cancer. Because people with various types of cancers were included in the studies reviewed, the current evidence suggests that exercise may benefit people with different diagnoses who are undergoing these treatments.

Communication of the evidence among physicians, nurses, and physical therapists will help in the creation of an exercise program for people who are hospitalized following stem cell transplantation. Future studies should consider the optimal means of putting an exercise program into practice, the effectiveness of different types of exercise, and a cost-benefit analysis of the implementation of an exercise program in the clinical pathway.

Based on the physical therapist examination and the results of our literature search, we planned to provide an aerobic exercise program for this patient. Because the patient's body temperature was currently 37.7°C (99.8°F), we delayed starting the program until her temperature was below 37.5°C (99.5°F). In addition, we planned to monitor her temperature and platelet count in the medical record to determine if exercise should be interrupted.

The use of bed or bicycle ergometers for aerobic exercise is recommended, based on the results of the literature we reviewed. In our experience, however, some patients are uncomfortable sitting on a bicycle seat, and some may be unfamiliar with bed ergometers. Because aerobic exercise is defined as the rhythmic contraction and relaxation of large muscle groups over a prolonged period of time, other forms of aerobic exercise, such as walking or active range of motion, might provide similar benefits. Therefore, we might substitute an alternative exercise program of exercises that the patient is comfortable and confident in performing and that follows the time parameters of the literature review (60 seconds of exercise, 60 seconds of rest for a 30-minute duration as reported in Dimeo et al, 1999).

Heart rate response to exercise would be monitored, keeping in mind that the patient may be tachycardic at rest due to anemia or low-grade fever. Clinical signs and symptoms of cardiovascular stress and reports of prolonged fatigue after exercise might require an alteration in exercise intensity.


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PubMed Clinical Queries Search Screen. Reproduced with permission of the National Library of Medicine.

 

    References
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 Database used for search:...
 Strategy: Clinical Queries
 Keywords: exercise AND (stem...
 Selection of articles for...
 Clinical decision:
 References
 
  1. Hayes RB, Wilczynski N, McKibbon KA, et al. Developing optimal search strategies for detecting clinically sound studies in MEDLINE. J Am Med Inform Assoc.1994; 1:447–458.[Abstract/Free Full Text]

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