INTRODUCTION
Hematopoietic stem cell transplantation (HSCT) is widely recognized as a treatment option for hematopoietic disorders. 1 ) Advances in supportive care have significantly reduced transplantation-related mortality rates and improved post-transplantation survival. 2 ) Conversely, several alterations in physical functioning have been observed following HSCT. In a previous study, these factors were linked to side effects of cancer therapy. 3 ) Acute graft-versus-host disease (GVHD), a major complication, is provoked by lymphocytes taken from donors in HSCT. This condition is typified by selective damage to the skin, liver, and gastrointestinal tract. 4 ) Patients with acute GVHD usually require high-dose corticosteroids. 4 ) The role of corticosteroids revolves around the suppression of a donor lymphocyte-promoted immune attack on recipient tissues. Nonetheless, high-dose corticosteroid therapy can cause different adverse events, including skeletal muscle atrophy. 5 , 6 ) A study reported that corticosteroid-provoked muscle atrophy occurred in 40% of patients receiving high doses of corticosteroid medications. 7 )
Corticosteroid-induced muscle atrophy occurs in proximal limb muscles, particularly the quadriceps, as previously reported. 8 ) For this reason, patients undergoing HSCT often experience difficulty standing up, which significantly affects daily activities. A decline in the ability to stand up may contribute to delayed hospital discharge, reduced post-discharge independence, and limitations in activities of daily living. This is particularly true for patients who struggle to rise from a chair, get up from a floor, squat down, or pick an object from the floor. For this reason, analyzing the ability to rise when performing daily activities is crucial. Previous studies have identified male sex and low body mass index as risk factors for sarcopenia following HSCT. 9 ) In addition, post-HSCT muscle weakness is associated with disuse syndrome resulting from reduced physical activity, 10 ) malnutrition resulting from weight loss and low serum albumin levels, 11 ) and skeletal muscle atrophy resulting from high-dose corticosteroids. 3 , 12 , 13 ) However, no studies have adequately investigated the factors provoking the diminished ability to stand up following HSCT. Therefore, this study aimed to prospectively evaluate patients undergoing HSCT treatment and to monitor their post-treatment physical performance.
MATERIALS AND METHODS
Study Design and Patients
All patients undergoing HSCT at Hyogo Medical University Hospital between June 2022 and June 2024 were prospectively followed, and the presence or absence of physical performance decline was assessed during the study period. The following inclusion criteria were used: aged 18 years or older; fully available data on pre- and post-HSCT physical function. The following patients were excluded: those who had severe heart failure; those with bone tumors with spine, pelvic girdle, and lower extremity fracture risks; were not from Japan; had undergone re-transplantation in the same institution; had graft failure; could not tolerate an examination after HSCT. Subsequently, 60 patients were initially approved as participants.
This study was conducted in accordance with the tenets of the 2013 revision of the Declaration of Helsinki and was approved in 2022 by the Hyogo Medical University Research Ethics Committee (approval no. 4113). Written informed consent was obtained from all participants before study commencement.
Definition of Post-HSCT Physical Performance Decline
Post-HSCT physical performance decline was defined as a decrease of a minimum of 1 point on the Short Physical Performance Battery (SPPB) chair rise on hospital discharge based on a comparison with the pre-HSCT score. The pre-HSCT assessment was conducted between admission and the initiation of the conditioning regimen. The post-HSCT assessment was performed on day 45 after HSCT or, if patients were discharged before day 45, at the time of hospital discharge.
SPPB
The SPPB was administered following established protocols. It consists of three components—balance assessment, gait speed, and repeated chair stands—resulting in a score ranging from 0 to 12, where higher scores reflect better physical function. Among various tools for evaluating physical performance in older adults, the SPPB is widely regarded as one of the most reliable, valid, and responsive instruments. 14 ) In this study, the assessment was conducted in accordance with the official manual. 15 )
For the balance test, participants were asked to maintain three standing positions (side-by-side, semi-tandem, and tandem) for up to 10 s each. For gait speed, participants walked 4 m at their usual pace, and the time to complete the distance was recorded; the faster of two trials was used for scoring. For the chair stand test, participants were instructed to rise from a seated position five times as quickly as possible without using their arms, and the total time was measured.
Demographic, Clinical, and Diagnostic Data
Demographic and clinical variables analyzed in this study included age, sex, body mass index (BMI), Eastern Cooperative Oncology Group performance status (ECOG-PS), disease type, transplantation stem cell source, conditioning regimen, degree of human leukocyte antigen incompatibility, total corticosteroid dose and its duration in days, acute GVHD grade, time from HSCT to engraftment and discharge, and physical therapy adherence rate. For laboratory parameters, albumin, hemoglobin, and total protein levels, as well as the geriatric nutritional risk index (GNRI), were obtained from blood tests performed prior to HSCT. The following GNRI formula was used: GNRI = [1.489 × albumin (g/L)] + [41.7 × (body weight/ideal body weight)]. 16 ) For patients who had been administered corticosteroids, the therapeutic scheme included methylprednisolone (mPSL) and prednisolone (PSL). Total cumulative corticosteroid doses were shown in milligrams of PSL (1 mg of mPSL=1.25 mg PSL) per kilogram (body weight). The patient data were retrieved from the electronic medical record.
Pre-HSCT Physical Function Evaluation
Each measurement was performed before HSCT. Handgrip strength was assessed bilaterally using a handgrip dynamometer (Takei Scientific Instruments, Tokyo, Japan). Each hand was tested twice in a standing position with the arms fully extended at the sides. The maximum value from the two trials for each hand was identified, and the mean of the highest values obtained from both hands was used for analysis. Isometric knee extension strength was measured twice on each side with a hand-held dynamometer (Anima, Tokyo, Japan). Participants were seated on a chair with hips and knees flexed at 90°. The dynamometer sensor was fixed to the anterior aspect of the lower leg with a traction belt secured between the ankle level and the chair. The maximum value from the two trials on each side was determined, and the average of these maximal values was calculated and normalized to body weight. Body composition was analyzed in the supine position with a multifrequency bioimpedance analysis system (InBody S10; InBody, Tokyo, Japan). The skeletal muscle index (SMI) was calculated according to: SMI = appendicular skeletal muscle mass (kg)/height 2 (m). The extracellular water ratio (ECW/TBW) was calculated using the following formula: ECW/TBW = appendicular extracellular water/total body water. The phase angle was determined with the following formula: phase angle (◦) = arctangent (X/R) × (180/π) based on X (reactance) and R (resistance) at 50 kHz, where the value for a right hemisphere was considered. 17 )
Rehabilitation Intervention
Patients started physical and occupational therapies before HSCT and then continued them during the recuperation period up to discharge. Physical and occupational therapies were carried out in a physical therapy room or single-bed isolation rooms, where the patients performed exercises for 20–40 min/day for 5 days/week. The physical therapy program was composed of stretching exercises, resistance training for lower limbs, and endurance training using a cycle ergometer in the isolation room. Occupational therapy involved stretching exercises, resistance training for the upper limbs, and daily living activities.
Statistical Analysis
For the comparative analysis of physical performance before and after HSCT, the patients were allocated into two groups: decline group (patients with post-HSCT physical performance decline, defined as a decrease of at least 1 point in the chair rise item of the SPPB at hospital discharge compared with the pre-HSCT score); non-decline group (patients without post-HSCT physical performance decline, defined as no increase in chair rise score at hospital discharge compared with the pre-HSCT score). 14 ) Because the primary aim of this study was to evaluate standing ability, the chair rise component that directly reflects stand-up performance and lower-limb muscle strength was used as the main indicator rather than the SPPB total score.
Mean values and standard deviations were applied as the descriptive statistics of parametric data, whereas the median and interquartile range (IQR) were used for nonparametric data. Data for categorical variables were expressed as number and percentage. In the univariate analysis, the Mann–Whitney or chi-squared tests were performed for the comparative analysis of continuous and categorical covariates, respectively.
The variables of sex, conditioning, and acute GVHD grade were analyzed with the chi-squared test. The Mann–Whitney U-test was employed to evaluate SPPB, standing balance test, 4-m walk, five chair stands, ECOG-PS, total corticosteroid dose, time from HSCT to engraftment, time from HSCT to discharge, and physical therapy adherence. The student t -test was implemented to comparatively analyze age, BMI, handgrip strength, knee extension strength, SMI, ECW/TBW, phase angle, albumin, hemoglobin, total protein, and GNRI. To evaluate the magnitude of responsiveness, standardized effect sizes were calculated. In accordance with Cohen’s d, thresholds of 0.2, 0.5, and 0.8 were interpreted as indicating small, moderate, and large effects, respectively. 18 , 19 ) Similarly, for the Phi coefficient and Pearson’s correlation coefficient, cutoff values of 0.2, 0.3, and 0.5 were considered to reflect small, medium, and large levels of responsiveness. 18 , 19 )
For the multivariate analysis, multiple logistic regression (coded as 0 for absence of post-HSCT physical performance decline and 1 for the presence of post-HSCT decline) was applied to predict post-HSCT physical performance decline at hospital discharge, with the exclusion of multicollinearity. Factors with P <0.05 in the univariate analysis were considered significant and were entered into the multivariate model. Variance inflation factor (VIF) values were computed to assess multicollinearity among the covariates, and VIF values between 1 and 5 were considered to indicate no multicollinearity.
To outline the area under the curve (AUC) of factors analyzed by multiple logistic regression, the receiver operating characteristic (ROC) curve analysis was performed. Using Youden index quantification, the optimal cutoff values for predicting post-HSCT physical performance decline at hospital discharge were found. Throughout, significance was confirmed for P ≤0.05. EZR (version 4.4.2) was used in all statistical analyses.
RESULTS
As illustrated in Fig. 1 , 60 prospective patients scheduled for HSCT were selected, but 10 were excluded because of in-hospital death (n=3), severe generalized complications (n=4), and HSCT discontinuation (n=3). Of the remaining 50 patients enrolled in the study, 22 (44.0%) patients were included in the decline group and 28 (56.0%) were included in the non-decline group. The demographic and diagnostic data of the overall sample are summarized in Table 1 . The mean age of the patients was 49.6 years, and 50.0% of the patients were male. Hematological disorders included acute leukemia, malignant lymphoma, myelodysplastic syndrome, chronic myelogenous leukemia, aplastic anemia, and multiple myeloma. Steroid therapy was initiated in 48 (96.0%) patients. The median total corticosteroid dose was 39.0 mg/kg. GVHD was not observed in 21 patients. Among patients with GVHD, 12 had grade I, 14 had grade II, and 3 had grade III disease. The pre-HSCT ECOG-PS scores were 0 in 30 patients, 1 in 15 patients, 2 in 2 patients, and 3 in 3 patients. The average time to engraftment was 14.0 days and the average time from HSCT to discharge was 55.9 days. The physical therapy adherence was 89.5%.
Table 1.
Demographic clinical characteristics of HSCT patients
Data presented as mean ± standard deviation, number (percentage) or median (IQR). HLA, human leukocyte antigen.
| Characteristic | n=50 |
| Age, years | 49.6 ± 12.6 |
| Sex | |
| Male | 25 (50) |
| Female | 25 (50) |
| Height, cm | 164.3 ± 7.1 |
| Body weight, kg | 55.2 ± 9.1 |
| BMI, kg/m 2 | 20.4 ± 2.9 |
| Diagnosis | |
| Acute leukemia | 34 (68) |
| Malignant lymphoma | 6 (12) |
| Myelodysplastic syndrome | 4 (8) |
| Chronic myelogenous leukemia | 2 (4) |
| Aplastic anemia | 3 (6) |
| Multiple myeloma | 1 (2) |
| Stem cell source | |
| Peripheral blood stem cell | 26 (52) |
| Bone marrow | 4 (8) |
| Cord blood | 17 (34) |
| Autograft | 3 (6) |
| Conditioning | |
| Myeloablative | 7 (14) |
| Reduced intensity | 43 (86) |
| Donor | |
| HLA-matched/related | 3 (6) |
| HLA-matched/unrelated | 23 (46) |
| HLA-mismatched/related | 21 (42) |
| HLA-mismatched/unrelated | 0 (0) |
| Autologous | 3 (6) |
| Total corticosteroid dose, mg/kg | 39.0 (13.8–67.0) |
| Duration of corticosteroid dose, days | 56.5 (36.3–69.8) |
| Acute GVHD | |
| No | 21 (42) |
| Grade 1 | 12 (24) |
| Grade 2 | 14 (28) |
| Grade 3 | 3 (6) |
| Grade 4 | 0 (0) |
| ECOG-PS | |
| 0 | 30 (60) |
| 1 | 15 (30) |
| 2 | 2 (4) |
| 3 | 3 (6) |
| 4 | 0 (0) |
| Time to engraftment, days | 14.0 ± 4.2 |
| Time from HSCT to discharge, days | 55.9 ± 15.8 |
| Physical therapy adherence rate, % | 89.5 ± 8.4 |
The SPPB scores are shown in Table 2 . The discharge SPPB score of the decline group (12, IQR 12–12) was significantly lower than that of the non-decline group (9, IQR 8–9) (P = 0.01). Table 3 displays the pre-HSCT data of the patients together with some details of the HSCT treatment. The proportion of female patients was significantly higher in the decline group (P = 0.04, φ=0.28). The pre-HSCT BMI (P = 0.03, d = 0.61), pre-HSCT handgrip strength (P = 0.04, d = 0.61), pre-HSCT phase angle (P <0.01, d = 0.93), and pre-HSCT GRNI (P = 0.02, d = 0.77) were all lower in the decline group. The total corticosteroid dose was significantly greater in the decline group (P <0.01, r = 0.48). As a result, sex, BMI, handgrip strength, phase angle, GRNI, and total corticoid dose were included in the multivariate analysis.
Table 2.
SPPB scores
Data presented as median (IQR). a Patients without post-HSCT physical performance decline; b Patients with post-HSCT physical performance decline.
| Analysis | Pre-HSCT | P value | Effect size | Post-HSCT | P value | Effect size | ||
| Non-decline group a (n =28) | Decline group b (n=22) | Non-decline group a (n=28) | Decline group b (n=22) | |||||
| SPPB total score | 12 (12–12) | 12 (11–12) | 0.64 | r=0.07 | 12 (12–12) | 9 (8–9) | <0.01 | r=0.77 |
| Standing balance test | 4 (4–4) | 4 (4–4) | 0.40 | r=0.13 | 4 (4–4) | 4 (4–4) | 0.45 | r=0.11 |
| 4-m walk | 4 (4–4) | 4 (3–4) | 0.28 | r=0.16 | 4 (4–4) | 4 (3–4) | 0.11 | r=0.23 |
| Five chair stands | 4 (4–4) | 4 (4–4) | 0.74 | r=0.05 | 4 (4–4) | 1 (0–2) | <0.01 | r=0.80 |
Table 3.
Study participants pre-HSCT characteristics and HSCT data
Data presented as mean ± standard deviation, number (percentage) or median (IQR). a Patients without post-HSCT physical performance decline; b Patients with post-HSCT physical performance decline.
| Characteristic | Non-decline group a (n=28) | Decline group b (n=22) | P value | Effect size |
| Age, years | 49.8 ± 12.7 | 49.3 ± 12.6 | 0.89 | d=0.04 |
| Female | 10 (36) | 15 (68) | 0.04 | φ=0.28 |
| BMI, kg/m 2 | 21.2 ± 3.3) | 19.5 ± 2.0 | 0.03 | d=0.61 |
| ECOG-PS | 0 (0–1) | 0 (0–1) | 0.82 | r=0.03 |
| Handgrip strength, kg | 26.9 ± 7.9 | 22.4 ± 6.6 | 0.04 | d=0.61 |
| Knee extension strength, kgf/kg | 0.50 ± 0.18 | 0.50 ± 0.12 | 0.97 | d=0.00 |
| SMI, kg/m 2 | 6.6 ± 1.2 | 6.0 ± 0.8 | 0.06 | d=0.57 |
| ECW/TBW | 0.40 ± 0.01 | 0.40 ± 0.01 | 0.05 | d=0.00 |
| Phase angle, degrees | 4.8 ± 0.9 | 4.0 ± 0.8 | <0.01 | d=0.93 |
| Albumin, g/dl | 3.7 ± 0.5 | 3.5 ± 0.4 | 0.25 | d=0.44 |
| Hemoglobin, g/dl | 9.3 ± 1.7 | 9.1 ± 1.5 | 0.61 | d=0.12 |
| Total protein, g/dl | 6.1 ± 0.6 | 6.0 ± 0.5 | 0.61 | d=0.18 |
| GNRI | 95.5 ± 9.6 | 89.4 ± 4.8 | 0.02 | d=0.77 |
| Reduced-intensity conditioning | 22 (79) | 21 (96) | 0.2 | φ=0.18 |
| Acute GVHD >grade 2 | 10 (36) | 7 (32) | 1 | φ=0.00 |
| Total corticosteroid dose, mg/kg | 16.8 (8.3–44.7) | 65.2 (38.9–82.7) | <0.01 | r=0.48 |
| Time to engraftment, days | 13.5 (11.0–15.3) | 11.5 (10.0–16.8) | 0.52 | r=0.09 |
| Time from HSCT to discharge, days | 53.5 (47.8–61.0) | 58.0 (47.5–68.8) | 0.48 | r=0.10 |
| Physical therapy adherence rate, % | 90.7 (86.8–94.8) | 90.6 (84.1–97.0) | 0.92 | r=0.02 |
Table 4 shows the results of multiple logistic regression analysis for post-HSCT physical performance decline, which showed an independent association with total corticosteroid dose [odds ratio (OR), 1.03; 95% confidence interval (CI), 1.00–1.05]. In ROC curve analysis, the cutoff post-HSCT physical performance decline at discharge was set at 19.2 mg/kg, demonstrating 95.5% sensitivity, 57.1% specificity, and an AUC of 0.78 ( Fig. 2 ).
Table 4.
Results of multiple logistic regression of physical performance decline post-HSCT
| Variable | Odds ratio | 95% CI | P value | VIF |
| Total corticosteroid dose | 1.03 | 1.00–1.05 | 0.03 | 1.15 |
| Sex | 1.36 | 0.06–30.50 | 0.85 | 4.04 |
| BMI | 0.92 | 0.64–1.33 | 0.66 | 1.44 |
| Phase angle | 1.02 | 0.23–4.49 | 0.98 | 2.30 |
| Handgrip strength | 0.91 | 0.73–1.14 | 0.41 | 4.34 |
| GNRI | 0.94 | 0.80–1.10 | 0.42 | 1.79 |
DISCUSSION
This prospective study aimed to outline the prognostic factors of post-HSCT physical performance decline. The results revealed that the total corticosteroid dose during hospital stay demonstrated an independent correlation with post-HSCT physical performance decline. This study shows that total corticosteroid dose assessment during the hospital stay can help predict post-HSCT physical performance decline. In this study, 44% of patients demonstrated post-HSCT physical performance decline. This phenomenon was strongly predicted by a total corticosteroid dose. The total corticosteroid dose cutoff was identified at 19.2 mg/kg. To the best of our knowledge, this study is the first to examine cutoff values for total corticosteroid dose in predicting post-HSCT physical performance decline. In general clinical practice, systemic corticosteroids are administered at 0.5–1.0 mg/kg per day for mild acute GVHD and approximately 2.0 mg/kg per day for severe acute GVHD. 20 ) At our hospital, a subset of patients who underwent haploidentical HSCT received corticosteroids at 1 mg/kg per day starting on the day after HSCT, with tapering typically initiated after approximately day 15 depending on the severity of GVHD. 21 ) For example, in a 50-kg patient receiving corticosteroids at 1 mg/kg per day, the daily dose is 50 mg, and the cumulative dose corresponding to the cutoff value identified in this study (19.2 mg/kg; approximately 1000 mg) is reached after approximately 20 days of treatment. Clinically, we frequently observe that patients who accumulate this dose at around 20 days after initiation of corticosteroid therapy begin to experience difficulty standing, suggesting that corticosteroid-induced muscle weakness becomes functionally apparent at this point in time.
Previous studies have shown that progressive corticosteroid-induced myopathy developed in 40% of patients who underwent HSCT. 7 ) In addition, corticosteroid-induced myopathy in patients who underwent HSCT also showed a negative correlation between the total corticosteroid dose and muscle strength. 3 , 12 , 13 ) A study of patients with cystic fibrosis also found a correlation between corticosteroid dose and knee extension strength but found no correlation with changes in handgrip strength. Notably, corticosteroid-induced muscle weakness tends to affect lower-limb strength more than that of the upper limb. Therefore, lower-limb muscle weakness can be associated with physical performance decline, such as the ability to stand up. According to several studies, post-HSCT physical performance decline is characterized by adverse effects caused by GVHD, malnutrition caused by reduced food intake, and disuse syndrome caused by limited activities in a sterile room. 3 , 10 , 11 ) Interestingly, in this study, only the total corticosteroid dose demonstrated a significant effect on post-HSCT physical performance decline. These findings suggest that patients who are anticipated to receive high-dose corticosteroids after HSCT may be at increased risk of standing with difficulty, indicating the importance of careful monitoring of functional changes during corticosteroid administration. This cutoff can serve as an indicator of when standing up becomes challenging, alerting patients to prevent falls and determining the need for handrails.
This study has several limitations. First, the results may not be generalizable, because they were based on data from a single tertiary care facility. Second, the sample size was relatively small (n=50), which may have limited the statistical power to fully assess the predictors of post-HSCT physical performance decline, particularly given that the logistic regression model included five explanatory variables. Third, the patients who were unable to undergo physical function evaluation, possibly because of severe GVHD, were excluded. These exclusions were likely related to a physical performance decline, but we unable to evaluate this correlation. Fourth, only pre-HSCT physical function was considered as a potential predictor, and changes in physical function from before to post-HSCT were not considered. Fifth, the potential influence of deconditioning could not be fully accounted for in this study. Despite these limitations, this study, examining the relationship between corticosteroid treatment and physical performance decline, has important implications for elaborating recovery strategies for patients who undergo HSCT.
CONCLUSION
The results of this study revealed that the total corticosteroid dose administered during the hospital stay was useful in predicting post-HSCT physical performance decline. Therefore, patients who are expected to receive high corticosteroid doses as a treatment of acute GVHD during HSCT should be evaluated with caution when they attempt to stand up.
ACKNOWLEDGMENTS
This study was supported by the Japan Society for the Promotion of Science (Grant Number 22H04422). We thank the therapists of the Department of Rehabilitation, Hyogo Medical University Hospital, as well as the patients and their families for their participation and cooperation.
Footnotes
CONFLICTS OF INTEREST: The authors declare no conflict of interest.
REFERENCES
1. Copelan EA: Hematopoietic stem-cell transplantation. N Engl J Med 2006;354:1813–1826. 10.1056/NEJMra052638
2. Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT), Japan Society for Transplantation and Cellular Therapy (JSTCT): Hematopoietic stem cell transplantation in Japan: annual report of nationwide survey 2021. Jpn J Transpl 2022;57:279–288.
3. Hamada R,Kondo T,Murao M,Miyasaka J,Yoshida M,Nankaku M,Kanda J,Takaori-Kondo A,Ikeguchi R,Matsuda S: Effect of the severity of acute graft-versus-host disease on physical function after allogeneic hematopoietic stem cell transplantation. Support Care Cancer 2020;28:3189–3196. 10.1007/s00520-019-05124-1
4. Ferrara JL,Levine JE,Reddy P,Holler E: Graft-versus-host disease. Lancet 2009;373:1550–1561. 10.1016/S0140-6736(09)60237-3
5. Pereira RM,Freire de Carvalho J: Glucocorticoid-induced myopathy. Joint Bone Spine 2011;78:41–44. 10.1016/j.jbspin.2010.02.025
6. Schakman O,Gilson H,Thissen JP: Mechanisms of glucocorticoid-induced myopathy. J Endocrinol 2008;197:1–10. 10.1677/JOE-07-0606
7. Lee HJ,Oran B,Saliba RM,Couriel DM,Shin K,Massey P,Neumann J,de Lima M,Champlin R,Giralt S: Steroid myopathy in patients with acute graft-versus-host disease treated with high-dose steroid therapy. Bone Marrow Transplant 2006;38:299–303. 10.1038/sj.bmt.1705435
8. Minetto MA,Lanfranco F,Motta G,Allasia S,Arvat E,D’Antona G: Steroid myopathy: some unresolved issues. J Endocrinol Invest 2011;34:370–375. 10.1007/BF03347462
9. Morishita S,Kaida K,Tanaka T,Itani Y,Ikegame K,Okada M,Ishii S,Kodama N,Ogawa H,Domen K: Prevalence of sarcopenia and relevance of body composition, physiological function, fatigue, and health-related quality of life in patients before allogeneic hematopoietic stem cell transplantation. Support Care Cancer 2012;20:3161–3168. 10.1007/s00520-012-1460-5
10. Morishita S,Kaida K,Yamauchi S,Wakasugi T,Ikegame K,Ogawa H,Domen K: Relationship of physical activity with physical function and health-related quality of life in patients having undergone allogeneic haematopoietic stem-cell transplantation. Eur J Cancer Care 2017;26:e12669. 10.1111/ecc.12669
11. Stauder R,Augschoell J,Hamaker ME,Koinig KA: Malnutrition in older patients with hematological malignancies at initial diagnosis—association with impairments in health status, systemic inflammation and adverse outcome. HemaSphere 2020;4:e332. 10.1097/HS9.0000000000000332
12. Hayakawa J,Miyamura D,Kimura S,Gomyo A,Tamaki M,Akahoshi Y,Harada N,Ugai T,Kusuda M,Kameda K,Wada H,Ishihara Y,Kawamura K,Sakamoto K,Sato M,Terasako-Saito K,Kikuchi M,Nakasone H,Kako S,Kanda Y: Negative impact of chronic graft-versus-host disease and glucocorticoid on the recovery of physical function after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2019;54:994–1003. 10.1038/s41409-018-0365-4
13. Morishita S,Kaida K,Yamauchi S,Sota K,Ishii S,Ikegame K,Kodama N,Ogawa H,Domen K: Relationship between corticosteroid dose and declines in physical function among allogeneic hematopoietic stem cell transplantation patients. Support Care Cancer 2013;21:2161–2169. 10.1007/s00520-013-1778-7
14. Freiberger E,de Vreede P,Schoene D,Rydwik E,Mueller V,Frändin K,Hopman-Rock M: Performance-based physical function in older community-dwelling persons: a systematic review of instruments. Age Ageing 2012;41:712–721. 10.1093/ageing/afs099
15. Puthoff ML: Outcome measures in cardiopulmonary physical therapy: short physical performance battery. Cardiopulm Phys Ther J 2008;19:17–22. 10.1097/01823246-200819010-00005
16. Bouillanne O,Morineau G,Dupont C,Coulombel I,Vincent JP,Nicolis I,Benazeth S,Cynober L,Aussel C: Geriatric Nutritional Risk Index: a new index for evaluating at-risk elderly medical patients. Am J Clin Nutr 2005;82:777–783. 10.1093/ajcn/82.4.777
17. Kyle U,Bosaeus I,De Lorenzo AD,Deurenberg P,Elia M,Gómez JM,Heitmann BL,Kent-Smith L,Melchior JC,Pirlich M,Scharfetter H,Schols AM,Pichard C, Composition of the ESPEN Working Group: Bioelectrical impedance analysis—part I: review of principles and methods. Clin Nutr 2004;23:1226–1243. 10.1016/j.clnu.2004.06.004
18. Cohen J: Statistical power analysis for the behavioral sciences. Lawrence Erlbaum, Hillsdale, 1988.
19. Durlak JA: How to select, calculate, and interpret effect sizes. J Pediatr Psychol 2009;34:917–928. 10.1093/jpepsy/jsp004
20. Mielcarek M,Furlong T,Storer BE,Green ML,McDonald GB,Carpenter PA,Flowers ME,Storb R,Boeckh M,Martin PJ: Effectiveness and safety of lower dose prednisone for initial treatment of acute graft-versus-host disease: a randomized controlled trial. Haematologica 2015;100:842–848. 10.3324/haematol.2014.118471
21. Ikegame K,Yoshida T,Yoshihara S,Daimon T,Shimizu H,Maeda Y,Ueda Y,Kaida K,Ishii S,Taniguchi K,Okada M,Tamaki H,Okumura H,Kaya H,Kurokawa T,Kodera Y,Taniguchi S,Kanda Y,Ogawa H: Unmanipulated haploidentical reduced-intensity stem cell transplantation using fludarabine, busulfan, low-dose antithymocyte globulin, and steroids for patients in non-complete remission or at high risk of relapse: a prospective multicenter phase I/II study in Japan. Biol Blood Marrow Transplant 2015;21:1495–1505. 10.1016/j.bbmt.2015.04.012