Improvement in the Physical Function and Quality of Life through Exercise and Physical Activity Intervention Using a Smartphone after Allogeneic Hematopoietic Cell Transplantation: A Case Report

Abstract

Purpose: Physical activity (PA) interventions positively affect the physical function (PF) in patients with advanced cancer. However, patients must remain motivated during the intervention. We report a case wherein a smartphone application for PA intervention was useful in motivating the patient to improve adherence. Methods: A 40-year-old woman underwent an allogeneic hematopoietic cell transplantation (allo-HCT) for an advanced extranodal natural killer/T-cell lymphoma. On day 6, she developed the posterior reversible encephalopathy syndrome. She was managed in the intensive care unit for 3 days, and her PF declined markedly. We initiated a smartphone-based PA intervention from day 35. She was instructed to maintain a PA diary for self-monitoring of the daily steps and to set a new step-count goal every week. Results: The PA and PF improved within a short period thereafter. However, she developed severe acute graft-versus-host disease and was administered with high-dose systemic corticosteroids from day 49. The PA, PF, and quality of life (QOL) decreased again. The intervention was continued for 5 months with a high adherence. The PA, PF, and QOL improved gradually. She resumed independent activities of daily living and was discharged on day 202. Conclusion: Smartphone-based PA intervention may be effective against post-allo-HCT physical dysfunction.

Extranodal natural killer/T-cell lymphoma (ENKL) is a rare lymphoma. Patients with advanced stage and relapsed/refractory ENKL have a dismal prognosis even after chemotherapy or chemoradiotherapy¹⁾. Although allogeneic hematopoietic cell transplantation (allo-HCT) is an effective and curative treatment for advanced and relapsed/refractory ENKL, a portion of the patients develop severe complications (such as the graft-versus-host disease [GVHD]) after an allo-HCT¹⁾. These complications limit the physical and psychological functions, which in turn decrease the quality of life (QOL)^2,3). Exercise has been identified as a strategy to mitigate these problems. However, in patients who develop severe complications or require intensive care, exercise alone is insufficient to recover the optimum physical function (PF)^2,3). Therefore, a new strategy is needed to improve the PF and QOL in patients who develop severe complications after an allo-HCT.

Previous studies have shown that physical inactivity is a major factor associated with a PF decline after an allo-HCT⁴⁾. In patients with colorectal cancer, physical activity (PA) interventions positively affect the PF and QOL⁵⁾. However, patients often experience difficulty in continuing the interventions due to a lack of motivation; a major reason is that they have to wear special devices, such as pedometers, to monitor the PA.

Although PA has been assessed mainly with pedometers in the past, a smartphone accelerometer application was developed recently, which is easy to use, validated for PA measurement⁶⁾, and has higher adherence to interventions than pedometers⁷⁾. Furthermore, smartphone-based PA interventions can effectively improve self-efficacy⁸⁾, leading to promoting PA^9,10). Although the smartphone accelerometer application has these advantages, there is no consensus on the best behavior change theory or model that should be used in smartphone-based interventions for PA promotion¹¹⁾. In addition, reports of its implementation in patients after an allo-HCT are lacking. Herein, we report a case of a patient with ENKL who suffered from physical dysfunction due to severe complications after an allo-HCT, and improved following exercise and a smartphone-based PA intervention.

Case Presentation

A 40-year-old woman was referred to our hospital for a high fever and hepatosplenomegaly. She was diagnosed with an advanced ENKL (nasal type). A chemotherapy regimen comprising dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide was initiated; however, it was switched to another chemotherapy regimen comprising gemcitabine, carboplatin, and dexamethasone (GCD) due to disease progression. After three cycles of GCD, she achieved partial remission and underwent an allo-HCT. Before the allo-HCT, the PF was evaluated using the following: 1) 10-meter walk test (10MWT), 2) 30-second chair stand test (30CST), and 3) 6-minute walk distance (the total distance walked back and forth over a distance of 30 m repeatedly for 6 minutes). The QOL was also evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30. She was instructed to complete an exercise program before and after the allo-HCT to maintain her PF and QOL. The exercise program comprised specific resistance training and aerobic exercise¹²⁾. The resistance training consisted of one set of 20–30 flexion and extension exercises of the hip, knee, and elbow joints with 0–1.5-kg loads and two sets of 10 standing calf raises. The aerobic exercise consisted of walking, with 3–10 minutes of ergometer. The exercise intensity was set to “somewhat hard” and rated as “4” on the modified Borg scale. The exercise program was implemented for 20–40 minutes a day, five times a week. After a conditioning regimen of fludarabine and melphalan, she received a peripheral blood stem cell transplant from a human leukocyte antigen-matched sibling donor. GVHD prophylaxis consisted of tacrolimus and methotrexate. On day 6, she developed disturbance of consciousness and seizures. Brain magnetic resonance imaging revealed multiple hyperintense areas on T2-fluid-attenuated inversion recovery (Fig. 1); thus, she was diagnosed with the posterior reversible encephalopathy syndrome (PRES). She was intubated and transferred to the intensive care unit (ICU), wherein she received mechanical ventilation for three days. PRES was resolved after discontinuation of tacrolimus and initiation of methylprednisolone (2 mg/kg/day). She was extubated and returned to the HCT ward on day 9. She achieved neutrophil engraftment on day 11. Although she followed the exercise program routinely, except for on the day of the ICU admission, her PF markedly decreased on day 28 (Fig. 2); she was unable to perform the 30CST. Her QOL also decreased (Fig. 3). Furthermore, the daily average step count, calculated per week using a smartphone accelerometer application, was only 2765 steps; this is below the average Japanese middle-aged woman’s step count of 7600 steps a day¹³⁾. Her exercise program was insufficient; therefore, PA intervention was included in the program¹⁴⁾ from day 35. She was instructed to maintain a PA diary to self-monitor the daily steps. At each weekly evaluation, she was instructed to set a new step-count goal, which was calculated by adding 400 steps to the average step count of the most recent seven days¹⁴⁾. After the introduction of the PA intervention, the PA (measured by steps) increased, and the PF and QOL improved within two weeks (Figs. 2 and 3).

Fig. 1.

Magnetic resonance imaging findings of PRES

Magnetic resonance imaging of the brain showed multiple areas of hyperintensity on T2-FLAIR in bilateral frontal and parietal lobes (A), right occipital lobe (B), and bilateral cerebellum (C). The arrows indicate lesions.

PRES, posterior reversible encephalopathy syndrome; FLAIR, fluid-attenuated inversion recovery

Fig. 2.

Clinical course of PF and PA, and the dose of corticosteroid

A smartphone-based PA intervention was initiated from day 35, and the PA and PF improved within a short period. However, she developed severe acute GVHD and was administered with high-dose systemic corticosteroids from day 49. The PA and PF decreased again. The intervention was continued for 5 months with a high adherence. The PA and PF improved gradually.

PF, physical function; PA, physical activity; GVHD, graft-versus-host disease

Fig. 3.

Clinical course of QOL

A smartphone-based PA intervention was initiated from day 35, and QOL also improved within a short period. However, QOL declined with the onset of GVHD, which then improved after 5 months of highly adherent PA intervention.

QOL, quality of life; PA, physical activity; GVHD, graft-versus-host disease

The methylprednisolone dose was gradually tapered; however, she developed grade III acute GVHD with gastrointestinal involvement on day 49. Therefore, the methylprednisolone dose was increased to 2 mg/kg/day. Furthermore, antithymocyte globulin (1 mg/kg) was administered on day 52, and mesenchymal stromal cells were administered on day 56. The average steps at day 56 markedly decreased to 201 with worsening physical symptoms, such as fatigue, abdominal pain, diarrhea, and anorexia, due to severe GVHD (Fig. 4). On day 63, her PF and QOL also decreased. During systemic steroid therapy for GVHD and while tapering the steroids, the exercise program and PA intervention were continued with high adherence (exercise program adherence: 96.2%, PA intervention adherence: 100%). By day 161, her average step count gradually improved to 6755, the 10MWT time improved to 6.84 seconds (Fig. 2), the global QOL score improved to 75.0 (Fig. 3), and she resumed independent activities of daily living. She was discharged on day 202, although she was still unable to perform the 30CST.

Fig. 4.

Clinical course of symptoms

A smartphone-based PA intervention was initiated from day 35, and the patient’s symptoms showed an overall improvement within a short period. However, some of her physical symptoms, such as fatigue, abdominal pain, diarrhea, and anorexia, worsened due to severe GVHD. After 5 months of adherence to PA intervention, her physical symptoms also showed improvement.

PA, physical activity; GVHD, graft-versus-host disease

Discussion

Physical dysfunction is often observed in patients after an allo-HCT⁴⁾. The effectiveness of exercise for such physical dysfunction has been established¹²⁾, and all patients who receive an allo-HCT at our hospital are instructed to participate in an exercise program composed of resistance training and aerobic exercise¹²⁾. In the present case, despite exercising, her PF markedly decreased on day 28 after developing PRES.

In previous studies, physical inactivity was the main factor for the decline in the PF after an HCT⁴⁾. In fact, our patient’s step count at day 28 was lower than that of Japanese women of the same age¹³⁾, suggesting physical inactivity. Recent studies have reported that PA intervention improved the daily step count^9,10). Furthermore, it also has positive effects on PF, symptoms, and QOL¹⁵⁾. Therefore, we focused on PA and proceeded with a new approach of adding a PA intervention to the exercise program in accordance with a previous study¹⁴⁾.

Although the effectiveness of PA intervention has been reported, there are problems with motivation and adherence. To address these, in this case, a smartphone was used instead of a pedometer to measure the step count⁷⁾. In addition, since self-monitoring is important to increase the adherence to the program, we instructed the patient to monitor the number of daily steps herself through a PA diary. We also instructed her to set a new step-count goal every week based on the diary. After the introduction of the PA intervention, the PA (measured by steps) increased and PF improved, as seen in previous studies^9,10). Although the benefits of PA interventions have been reported to be achieved mainly after 4−8 weeks or longer¹⁶⁾, her PF and QOL improved within just 2 weeks. There are several reasons for this rapid improvement. First, the use of a smartphone to measure the step count was a factor that increased adherence and allowed us to monitor the daily steps accurately without a lapse. Second, the PA intervention used in this case was a multi-component intervention. In a previous study on PA intervention, it was reported that a multi-component intervention appears to more effective than a stand-alone application intervention¹⁷⁾. The patient was instructed to measure her steps, keep a PA diary, and set a new step-count goal every week. Self-monitoring of daily steps helped make aware of her daily PA, which motivated her to become more physically active and achieve the new weekly goals¹⁸⁾. These strategies that were aimed to facilitate a behavioral change and to increase adherence to the program led to successful improvement in the PA and PF.

After approximately 5 months of the exercise program and PA intervention, her average steps, gait velocity, and QOL improved considerably. However, her 30CST scores, which reflect the muscle strength of the lower extremities, did not improve. A previous study revealed that a high dose of corticosteroids was correlated with a decrease in the knee extensor muscle strength after a hematopoietic stem cell transplantation¹⁹⁾. Furthermore, the GVHD and corticosteroid usage were the independent risk factors for a delayed recovery of the muscle strength³⁾. The effect of exercise and our PA intervention was insufficient to recover the decline in the muscle strength of the lower extremities due to high-dose steroid therapy for severe GVHD. In previous studies, moderate exercise therapy, similar to our approach, has been recommended for steroid myopathy²⁰⁾. However, this approach may be insufficient in patients receiving high-dose and long-term steroid therapy, such as ours.

This case report has several limitations. First, factors other than PA intervention, such as an improvement of the GVHD, might have affected improvements in the PF and QOL. Second, we did not evaluate the daily steps before day 28. Third, only smartphone usage was examined, and a comparison of its outcomes with those of pedometer usage was not possible.

Conclusion

This case suggests that PA intervention using a smartphone may be an effective strategy in patients with physical dysfunction due to severe complications after an allo-HCT. The intervention used in this case can be applied to any patient, at any given time and place, as long as the patient has a smartphone. Further studies with a large number of patients are needed.

Acknowledgments

The authors thank the members of the Department of Musculoskeletal Oncology and Rehabilitation and the Department of Hematopoietic Stem Cell Transplantation at the National Cancer Center Hospital for their support, without which a compilation of this report would not have been possible. This study was supported in part by JSPS KAKENHI, Grant Number 19K24301.

Informed Consent

Patient’s written informed consent was obtained for publication of this case report.

Conflict of Interest

The authors declare that they have no conflict of interest.