Abstract
Objective
We aimed to investigate the acute physiological responses (APR) to physiotherapy applications in patients undergoing autologous stem cell transplantation (ASCT), the difference between pre- and post-ASCT according to APR.
Methods
Twenty-six patients who were hospitalized for ASCT attended regular physiotherapy program. APR was recorded in the beginning and at the end of each exercise session. The differences in APR were calculated for each session. The mean values of the differences in APR were computed in pre-conditioning, pre-, and post-ASCT. Daily complete blood counts were also recorded during ASCT.
Results
Hemoglobin and platelet counts were significantly lower pre- and post-ASCT. Neutrophil counts were significantly lower post-ASCT. The difference in systolic blood pressure (SBP) in the beginning and at the end of the exercise sessions was significantly higher post-ASCT in comparison to pre-ASCT.
Conclusion
There was no significant change in APR except the SBP which suggests that similar level of exercise intensity could be tolerated in pre- and post-ASCT periods as well as preconditioning.
Introduction
High-dose chemotherapy (HDC) combined with autologous stem cell transplantation (ASCT) has become the standard of care and offer the potential to cure some hematologic malignanciesCitation1 including multiple myeloma and (non-)Hodgkin's lymphoma.Citation2,Citation3 Treatment-related acute toxicity can be quite highCitation1 and chemotherapeutic agents may also have long-term side effects.Citation2 Physical exercise has been demonstrated to be an effective strategy for patients with cancer and stem cell transplantation (SCT) recipients.Citation4 Physical exercise interventions during hospitalization for SCT had no unexpected or negative effects.Citation4–Citation6 Exercise seems to be generally safe, effective, and capable of providing functional improvements in this population.Citation7 Many previous studies have demonstrated that cancer patients benefit from exercise in terms of improved cardiorespiratory fitness, physical functioning, and fatigue symptoms.Citation8–Citation10 Physical exercise in SCT patients was also shown to have positive effects on functional capacity,Citation8,Citation9 hemoglobin concentration,Citation9 duration of neutropenia and thrombocytopenia, severity of diarrhea and pain, duration of hospitalization,Citation8 and quality of life.Citation4 Moreover, the regular physical exercise interventions during SCT were also demonstrated to have positive effectsCitation4–Citation6 on muscle strength,Citation5,Citation11 muscle endurance,Citation5,Citation12 relative endurance capacity, and physical performance.Citation13
The acute physiological responses (APR) are of note in SCT patients as they provide information regarding the medical status, activity level, and exercise tolerance of the individuals.Citation14,Citation15 Interpreting patient's responses to exercise is important in determining the patients’ compliance to treatment in the setting of ASCT. In this respect we investigated the acute physiological changes in response to physiotherapy applications in patients undergoing ASCT. We hypothesized that the acute hemodynamic responses to exercise would differ pre- and post-ASCT. This is the first study investigating the influence of exercise in adult ASCT recipients to the best of our knowledge.
Materials and methods
The study was conducted in patients hospitalized at the Bone Marrow Transplantation Unit between January 2010 and 2012. Twenty-six patients, who were hospitalized for ASCT, were enrolled into the study. The study group consisted of 14 women and 12 men. The median age of the study group was 48.5 (19–64) years. The criteria for excluding the patient from the exercise program were
| 1. | Extensive osteolytic lesions with risk of fracture or spinal cord compression | ||||
| 2. | Serious cardiorespiratory and/or cardiovascular conditions | ||||
| 3. | Severe infections | ||||
| 4. | Severe anemia | ||||
| 5. | Severe cognitive or emotional instability that limits exercise cooperation and compliance | ||||
| 6. | Other disabling comorbidities interfering with the intervention program or influencing outcome parameters (e.g. having a pacemaker, epileptic seizures and/or poorly regulated diabetes mellitus). | ||||
The local ethical committee approved the study on 11 April 2012 (the decision no: 153), and all patients gave informed consents.
The voluntary participants were implemented a regular physiotherapy program which was supervised by the same physiotherapist during hospitalization for ASCT. Eligibility criteria for exercise program were
| 1. | Hemoglobin (Hb) ≥7 g/dl, | ||||
| 2. | White blood cell count >2.0 × 109/l, | ||||
| 3. | To be able to cycle on a bicycle ergo meter, | ||||
| 4. | To be able to walk at least 100 m independently. | ||||
Hemoglobin, white blood cell count, and platelet counts were checked daily and the patients who did not meet the inclusion criteria skipped the exercise program that day. After red blood cell and platelet transfusion or defervesence physiotherapy program was restarted.
The physiotherapy program consisted of reciprocal active joint movements for 10 minutes, breathing exercises combined by breathing control and deep inspirium by triflow for 5 minutes, walking on treadmill or biking on a stationary bike at the level that patient felt him/herself comfortable for 10 minutes. The exercise sessions were hold for 25 minutes at every working day in the morning between hours 09.00–12.00, during hospitalization for stem cell transplantation (5–7 days for conditioning, 2–3 weeks for transplantation). Every exercise session was supervised by specialized physiotherapist.
Acute physiologic responseCitation16 including blood pressure, heart rate, respiratory rate, oxygen saturation, and physical exhaustion level on Borg centiMax (CR100) scaleCitation17 were recorded before and after every physiotherapy session. The differences in each session were calculated. The blood pressure was measured by Sphygmomanometer (Erka-Germany), heart rate and oxygen saturation was recorded by pulse oximetry (Contec CMS-60A-China), and respiratory rate was assessed manually by the physiotherapist.
At the first day of hospitalization, conditioning regimens were not started yet, was called as ‘pre-conditioning’. The APR to exercise between hospital admissions till stem cell infusion while conditioning was calculated and used as ‘pre-ASCT’ and between stem cell infusions till discharge was called as ‘post-ASCT’. The mean values of differences in APR between before and after exercise were computed pre-conditioning, pre- and post-ASCT. Daily laboratory values (hemoglobin, platelet, neutrophil) were also recorded and mean values were calculated for each term separately.
Data analysis
All data were analyzed with the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA) version 17.0. ‘Kolmogorov–Smirnov test’ was used to determine the normality of distribution. Saturation and hemoglobin data did not distribute normally. Therefore, ‘Friedman test’ was used to compare the differences in these parameters pre- and post-ACST. All P values were two-sided with statistical significance at 0.05 alpha levels. ‘Repeated measures analysis of variance test’ was used to compare difference in systolic and diastolic blood pressure, heart rate, respiratory rate, Borg centiMax (CR100) scores, platelet, and neutrophil counts which distributed normally.
Results
The patient characteristics of age, gender, diagnosis, and chemotherapeutic agent used in the conditioning regimen are shown in .
Table 1. The patient characteristics and chemotherapeutic agents used in the conditioning regimen
The patients participated to median 3 (1–5) physiotherapy sessions before and median 6 (2–8) physiotherapy sessions post ASCT. Hemoglobin and platelet counts were significantly lower pre- and post-ASCT (P < 0.05). Neutrophil counts were significantly lower post ASCT (P < 0.05). The difference of neutrophil between pre-conditioning and pre-ASCT was not significant (P > 0.05) ().
Table 2. Complete blood counts pre and post ASCT
The mean difference in systolic blood pressure between the beginning and the end of the exercise sessions was 5.00 (10.67) in pre-conditioning group, 7.71 (8.47) in pre-ASCT period, and 2.81 (7.08) in the post-ASCT period. The difference between pre- and post-transplantation period was significant (P < 0.05), pre-conditioning and pre-transplantation, pre-conditioning and post-transplantation were not significant (). The differences in diastolic blood pressure, heart rate, respiratory rate, and Borg centiMax (CR100) scores were similar in between pre-conditioning, pre–transplantation, and post-transplantation in the beginning and at the end of the exercise session (P > 0.05) ().
Table 3. The difference between before and after exercise session of systolic and diastolic blood pressure, heart and respiratory rate and Borg centiMax (CR100) Scale in preconditioning, pre-ASCT and post-ASCT
The mean difference in saturation scores was −0.19 (1.38) in pre-conditioning group, −0.10 (1.60) in pre-transplantation group, and 0.33 (1.33) in post-transplantation group. There were no significant differences in saturation between pre-conditioning, pre–transplantation, and post-transplantation (P > 0.05) ().
Table 4. The difference between before and after exercise session of oxygen saturation in preconditioning, pre ASCT and post ASCT
Discussion
The most important implication of the presented study is that the systolic blood pressure response to exercise loading decreased significantly in post-ASCT period compared to pre-ASCT period. Previous report was demonstrated that systolic blood pressure in resting was mildly lower in the post-transplantation period compared to healthy subjects.Citation18 In the study by Larsen et al. systolic blood pressure response was demonstrated to be reduced after exercise in the pre transplantation period in contrast to our results. Our study did not include healthy controls, however, similar to previous study systolic blood pressure in the resting condition prior to the exercise decreased mildly after transplantation compared to the pre-transplantation levels (104.15 vs. 106.4 P = 0.008).
Cardiac toxicity has been reported with some chemotherapeutic agents such as melphalan, carmustine, etoposide, cytarabine, melphalan, thiotepa, cyclophospamide, busulfan, fludarabine all of which have been used in our patients as well. Cardiac dysfunction may also occur either during or soon after (within 3 weeks to months) after HDC.Citation19–Citation23 Nonspecific and transient electrocardiogram abnormalities and decline in left ventricular ejection fraction have been reported following administration of HDC, all of which turn back to baseline usually within a few days or weeks.Citation24,Citation25 Diastolic blood pressure measurement was preferred for the evaluation of subclinical cardiac toxicity in patients receiving chemotherapy, as it was observed that diastolic alterations occurred earlier.Citation26 Nevertheless, there was no significant change in parameters such as diastolic blood pressure, respiratory rate, oxygen saturation, and heart rate between pre- and post-ASCT in this study. This finding suggested that ASCT did not affect acute hemodynamic responses to exercise except systolic blood pressure. In other words similar level of exercise intensity could be tolerated by patients in pre- and post-ASCT periods.
Another explanation for the decreased systolic blood pressure response to exercise in the post-transplantation period might be the relatively low intensity and duration of the exercise applied in this study. The program in fact might have been too light to induce a change in APR in the post-ASCT period. However, we preferred a light exercise program as the ASCT recipients cannot tolerate intensive exercise programs in this period. In this study, it was observed that patients could tolerate and complete the exercise program. Although some patients complained about dyspnea, fatigue, fever, they could continue and finish the exercise performance without any distress. Indeed the exercise intensity was recommended to be at moderate level in patients with SCT previously.Citation27
Beside the direct toxicity to myocardial tissue, chemotherapy also causes anemia, which decreases the oxygen transport capacity to myocardial tissue.Citation28 In our cohort, hemoglobin levels also decreased significantly at the post-transplantation period. Previous studies show that physiotherapy applications during SCT have a positive impact on blood counts. Dimeo et al.Citation8,Citation9 demonstrated that exercise mediated better physical performance at discharge, a shorter duration of hospitalization, neutropenia, and thrombocytopenia in the training group who performed regular daily exercise during hospitalization. Since we did not compare the laboratory values of the study cohort to a non-exercise control group, we cannot comment on the impact of exercise applications on neutrophil and platelet counts.
Limitations
According to patient circulation of SCT unit, the conditioning regimens were started one day after hospitalization and it was not possible to hospitalize and follow up patients before conditioning for longer duration therefore, pre-conditioning data included only one session.
Conclusion
Our study demonstrates the status of the APR in patients undergoing ASCT. There was no significant change in the physiological responses to exercise including diastolic blood pressure, heart rate, respiratory rate, oxygen saturation, and physical exhaustion level on Borg centiMax (CR100) scale, except the systolic blood pressure. In conclusion, ASCT does not seem to cause remarkable physiological responses to low-dose exercise and the same exercise programs can safely be implemented to ASCT recipients in the pre- and post-transplantation periods.
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