Bone Marrow Transplantation (2014) 49, 786–792 © 2014 Macmillan Publishers Limited All rights reserved 0268-3369/14 www.nature.com/bmt

ORIGINAL ARTICLE

Telephone-delivered nutrition and exercise counselling after auto-SCT: a pilot, randomised controlled trial Y-C Hung1, JD Bauer1,2, P Horsely2, J Coll2, J Bashford3 and EA Isenring1,4 Adverse changes in nutrition-related outcomes including quality of life (QoL) occur after PBSC transplantation. This randomised controlled trial aims to evaluate the impact of nutrition and exercise counselling provided at hospital discharge on nutritional status, body composition and QoL post transplantation. Usual care (UC) (n = 19) received no intervention after discharge; extended care (EC) (n = 18) received fortnightly telephone counselling from a dietitian and exercise physiologist up to 100 days post transplantation. Nutritional status (patient-generated subjective global assessment, and diet history), QoL (EORTC QLQ-C30 version 3) and body composition (air displacement plethysmography) were assessed at pre-admission, discharge and 100 days post transplantation. Intervention groups were compared using two-sample t-tests of changes in the outcomes; results were adjusted using analysis of covariance. EC exhibited clinically important but not statistically significant increases in protein intake (14.7 g; confidence interval (CI) 95% − 6.5, 35.9, P = 0.165), cognitive functioning (7.2; CI 95% − 7.9, 22.2, P = 0.337) and social functioning (16.5; CI 95% − 7.3, 40.3, P = 0.165) compared with UC. Relative to pre-admission, EC experienced less weight loss than UC (−3.3 kg; CI 95% − 6.7, 0.2, P = 0.062). Physical activity was not significantly different between the groups. Ongoing nutrition and exercise counselling may prevent further weight loss and improve dietary intake and certain QoL components in autologous PBSC transplantation patients following hospitalisation. Bone Marrow Transplantation (2014) 49, 786–792; doi:10.1038/bmt.2014.52; published online 7 April 2014

INTRODUCTION Approximately 10% of patients diagnosed with haematological malignancies in Australia are treated with high dose conditioning and PBSC transplantation.1 The treatment is accompanied by complications and side effects that adversely affect nutritional status,2,3 body composition,3,4 quality of life (QoL) and functioning capacity (that is, work)5 for prolonged periods of time. The role of nutrition intervention,6,7 exercise intervention8,9 or combined nutrition and exercise interventions10,11 amongst cancer survivors have shown to reverse or improve treatmentrelated side effects. However, these results may not be applicable to haematological cancer patients treated with PBSC transplantation as most studies were conducted on patients with solid tumours (that is, breast, prostate and colon). To date, several studies have examined the role of exercise across different phases of PBSC transplantation (that is, before, during and after hospital discharge),12–16 but no study has examined the role of nutrition support delivered by a dietitian amongst PBSC transplantation patients after hospital discharge. We have previously demonstrated that the immediate impact of transplantation on nutritional status, body composition, QoL and physical activity level (PAL) amongst a group of autologous PBSC transplantation patients resolved gradually over the first 100 days post transplantation. However, the deficit of lean body mass (LBM) remained notable, and one in three patients continued to experience nutrition impact symptoms.3 On the basis of our observational study, we were interested in whether the reversal of treatment-related adverse effects after hospital discharge would

be improved if patients were provided with ongoing nutrition counselling with the addition of exercise counselling following hospital discharge. In research settings, exercise has shown to optimise body composition and improve QoL amongst haematological cancer patients (with or without PBSC transplantation).17 At present, exercise is not provided as a part of standard inpatient care for PBSC transplantation patients. As the clinic which participated in this study provided a service to the state of Queensland (1 727 000 km2), a pilot study using telephone-delivered intervention was proposed to allow the inclusion of patients residing in rural or semi-rural areas where access to facilities providing nutrition or exercise counselling services may be limited. The aim of this pilot randomised controlled trial was to evaluate the feasibility (that is, safety and adherence) and the effectiveness of a home-based, telephone-delivered nutrition and exercise intervention on nutritional status, body composition, QoL and PAL amongst cancer patients treated with autologous PBSC transplantation up to 100 days post transplantation compared with those provided with usual care (UC).

PATIENTS AND METHODS This study was conducted based on our earlier findings.3 Eligible candidates were adult (⩾18 years old) haematological cancer patients scheduled for autologous PBSC transplantation from a single transplantation centre, the Haematology and Oncology Clinics of Australia, The Wesley Hospital, Brisbane, Australia. Patients undergoing allogeneic transplant or

1 Centre for Dietetics Research, School of Human Movement Studies, The University of Queensland, Brisbane, Queensland, Australia; 2The Wesley Research Institute, Brisbane, Queensland, Australia; 3Haematology & Oncology Clinics of Australia, The Wesley Medical Centre, Brisbane, Queensland, Australia and 4Department of Nutrition & Dietetics, Princess Alexandra Hospital, Brisbane, Queensland, Australia. Correspondence: Y-C Hung, Centre for Dietetics Research, School of Human Movement Studies, The University of Queensland, Building 26B, Brisbane, Queensland 4072, Australia. E-mail: [email protected] Received 12 July 2013; revised 24 January 2014; accepted 29 January 2014; published online 7 April 2014

Nutrition and exercise after stem cell transplant Y-C Hung et al

787 patients deemed unsuitable to participate in the study by their physicians were excluded. Ethics approval was granted by the multidisciplinary ethics committee of the hospital (ref: 1107) and The University of Queensland (ref: HMS11/2405.R1). The study is registered under the Australian New Zealand Clinical Trials Registry (ACTRN12611000194965). All patients provided written informed consent. Participants were consecutively recruited over 12 months plus 3 months to complete the final follow-up (15 May 2011–15 August 2012). During admission, all patients received best practice nutrition care delivered by an accredited dietitian who was experienced in the care for PBSC transplantation patients. Nutrition care included an initial nutrition assessment and counselling on the nutritional impact of PBSC transplantation at preadmission, followed by intensive nutrition support during hospitalisation involving frequent dietary reviews and the use of high-protein and -energy oral nutrition supplements or parenteral nutrition if required. Randomisation sequence was generated by block randomisation (single block of 60) using a randomisation programme (www.randomization.com). Group allocation was concealed from the principal investigator until post transplantation. On the week of discharge, patients were randomised to either UC or extended care (EC); allocation was non-blinded. UC received no further nutrition support after hospital discharge. The intervention was a 12-week home-based nutrition and exercise programme implemented at hospital discharge and continued to 100 days post transplantation. The first counselling session was delivered on the week of discharge which included goal setting and development of strategies; face-to-face counselling was important to build rapport. Each programme was individualised owing to the varying severity of treatment side effects amongst individuals, but in general, goals were set to improve nutritional status and physical functioning (that is, recover PAL before cancer treatment, or improve PAL if previously inactive). The nutrition component was delivered by an accredited dietitian and the exercise component was delivered by an accredited exercise physiologist. The framework for the nutrition intervention was based on the Academy of Nutrition and Dietetics nutrition care process,18 and the exercise recommendations were based on the American College of Sports Medicine guidelines for cancer survivors.19 Patients were encouraged to begin aerobic exercise daily (that is, walking or cycling) for ⩾ 10–30 min, and simple resistance exercise (that is, sit-to-stand with folded arms or free weight) for 3–7 days a week (10–20 repetitions). After discharge, patients were phoned fortnightly to evaluate progress when the goals and strategies (that is, intensity and length of exercises) were modified if required. The time and date for subsequent sessions was determined by both the practitioner and the patients at the end of each telephone review. If the patient could not be reached, the session was considered ‘missed’ with one failed attempt of recontacting the patients. The following session would be made in another fortnight’s time. Participants were expected to complete one inpatient counselling session and five follow-up telephone calls from each practitioner (total of 10 telephone calls). Feasibility was assessed by safety and adherence (patients receiving at least three out of five follow-up calls for both of the nutrition and exercise counselling). Measured outcomes included nutritional status, dietary intake, body composition, QoL parameters and PAL assessed by the principal investigator via face-to-face appointments (nutritional status, dietary intake and body composition) and self-administered questionnaires returned by mail (QoL and PAL). In the case where patients could not return to the hospital for assessments, nutritional status and dietary intake were obtained via a telephone call using a standardised assessment form20 and protocol.21 Change in patient outcomes at 100 days post transplantation (end of intervention) was compared with hospital discharge (start of intervention) for all outcomes except for body composition because patients received i. v. fluid (for example, saline and chemotherapy) during hospitalisation and frequently, this was not ceased until the day of discharge. Temporary fluid weight gain immediately after i.v. infusion has been demonstrated amongst healthy individuals.22 Excess hydration can mislead body composition results of air displacement plethysmography23 by temporarily increasing LBM.24 For these reasons, body composition was compared with pre-admission (median − 9.5 days, range − 21 to 9 days of transplantation) when nutritional status and hydration were stable. Nutritional status was assessed by the valid and reliable scored patientgenerated-subjective global assessment (PG-SGA);20,25 body composition (weight, fat mass (FM) and LBM) by air displacement plethysmography (Bod Pod, COSMED, Concord, CA, USA); and QoL using the EORTC QLQ-C30 (version 3)26 as detailed previously.3 © 2014 Macmillan Publishers Limited

Dietary intake was assessed with an interviewer-administered 7-day diet history adapted from the ‘interviewer-administered, open-ended structured diet history’.21 Energy and protein intake were analysed using FoodWorks, version 5 for windows (Xyris software Pty Ltd 2009, Brisbane, QLD, Australia). PAL over the last 7 days was determined using the Active Australia Survey.27 Responses were given by frequency (per week), and time (hours and minutes) spent on four types of activity including: continuous walking (minimum 10 min), moderate physical activities, vigorous physical activity (excludes gardening) and vigorous gardening or heavy work in the yard. PAL was coded as a continuous variable (total time in minutes for each activity except gardening) and categorical variable (sedentary, insufficient and sufficiently active) based on the scoring protocol.

Statistical analysis This was a pilot study. Sample size was based on the consecutive number of patients undergoing autologous PBSC transplantation who consented to the study over the 12-month recruitment period. Statistical analyses were performed using SAS software, Version 9.3 (SAS Institute Inc., Cary, NC, USA). Patient characteristics at hospital discharge were summarised as frequency and per cent for categorical variables, and by mean and s.d. (or median and interquartile range) for continuous variables. Differences between the groups at hospital discharge were compared using χ2 or Fisher's exact test for categorical variables and by the t-test or Mann–Whitney U-test for continuous variables. Changes in the nutrition and QoL outcomes were calculated by subtracting the value at hospital discharge from the value at 100 days post transplantation. Unadjusted results were compared using a two-sided two-sample t-test of the difference in the outcome from discharge. Mean and s.d. for each group along with the mean difference between groups and 95% confidence intervals (CI) of the difference are reported. Analysis of covariance was used to adjust the results for age, gender, diagnosis, length of hospital stay, PG-SGA score at hospital discharge and the change from preadmission to hospital discharge to account for the varying treatment side effects experienced amongst individuals. The results of the adjusted analyses are reported as least squares means with s.e. along with the difference in least squares means with 95% confidence limits (CI). Changes in body composition from pre-admission to 100 days post transplantation between groups were compared using two-sample t-test. Although statistical significance was set at a conventional level of P o0.05, the clinical importance of the results was also considered. A difference in protein intake of 10 g/day,28 energy intake of 1MJ,6 LBM of 1 kg29 and a difference in the global QoL score of >430 were determined a priori to be considered as clinically important.

RESULTS Thirty-seven patients were recruited (consent rate = 76%); patient characteristics were similar at hospital discharge (Table 1). Lymphoma patients were predominantly (94%) treated with BEAM, whereas multiple myeloma patients were primarily (90%) treated with Melphalan 200 mg/m2. At hospital discharge, the majority of patients (all UC, and 77% EC, P = 0.076) were malnourished (SGA B/C); UC had higher PG-SGA score (P = 0.018) and longer length of hospital stay (P = 0.042). See Figure 1 for recruitment, patient flow and assessments completed. Between hospital discharge and 100 days post transplantation, both groups improved in nutritional outcomes (Table 2). Unadjusted increase in protein intake favoured EC (+9.1 g, CI 95% − 11.4, 29.6, P = 0.372); the magnitude of improvement increased after adjustment (+14.7 g, CI 95% − 6.5, 35.9, P = 0.165). Change in PG-SGA score and energy intake was similar between the groups before and after adjustment of analysis. By 100 days post transplantation, the majority of patients were classified as well nourished (SGA A) (UC 65% and EC 75%, P = 0.708). Median PGSGA score remained higher amongst UC (median 7, interquartile range 4.5–11.0) than EC (median 3.5, interquartile range 2.0–7.5) (P = 0.039). On the basis of the scores attributed to nutrition impact symptoms in the PG-SGA, less EC (25%, n = 4/16) than UC (75%, n = 13/17) patients experienced one or more nutrition impact symptoms affecting eating (P = 0.003). Bone Marrow Transplantation (2014) 786 – 792

Nutrition and exercise after stem cell transplant Y-C Hung et al

788 Table 1. Characteristics of 37 patients treated with high dose conditioning and autologous peripheral blood stem cell transplantation at hospital dischargea Usual care N = 19 Age (years) Gender N (%) male Diagnosis N (%) Lymphoma Myeloma Weight (kg) BMI (kg/m2) BMI categories n (%) Underweight (BMIo18.5) Normal (BMI 18.5 to o 25) Overweight (BMI 25 to o 30) Obese (BMI ⩾ 30) Subjective global assessment rating20 A (well nourished) B (suspected malnourished) C (moderately malnourished)

59.9 ± 9.2 10 (52.6)

57.5 ± 9.8 10 (55.6)

9 10 69.5 24.1

8 10 74.0 25.4

1 7 3 3

(47.4) (52.6) (58.8–91.4)d (22.8–30.0)d (7.1) (50.0) (21.4) (21.4)

1 6 8 1

P-valueb 0.449 0.858 0.858c

(44.4) (55.6) (66.7–75.9)e (23.6–27.4)e

0.835f 0.728f 0.323g

(6.3) (37.5) (50.0) (6.3) 0.076g

0 (0.0) 12 (66.7) 6 (33.3)

4 (23.5) 10 (58.8) 3 (17.7)

21.2 ± 4.2h

16.4 ± 6.8i

Patient generated-subjective global assessment score Energy (kJ) Protein (g)

3895 ± 1829 45.0 ± 24.7h

Global quality of life Walking time (min) Moderate exercise (min) Vigorous exercise (min)

33.3 30.0 0.0 0.0

Physical activity level27 Sedentary Insufficiently active Sufficiently active Length of stay (days)

Extended care N = 18

h

(8.4–50.0)i (5.0–85.0)i (0.0–0.0)i (0.0–0.0)i

0.018

4166 ± 1496 46.3 ± 17.5e

e

33.3 30.0 0.0 0.0

(12.5, 45.9)i (0.0–85.0)i (0.0–0.0)i (0.0–0.0)i

0.643 0.857 0.792f 0.766f 0.317f 0.506f 0.880g

4 11 2 22.0

(23.5) (64.7) (11.8) (18.0–31.0)

6 9 2 18.0

(35.3) (52.9) (11.8) (16.0–21.5)i

0.042f

Abbreviation: BMI = body mass index. aValues presented as mean ± s.d. or median (interquartile ranges). bP-value is for differences between groups tested by two-sample t-tests, P o0.05. cP-value is for differences between groups tested by χ2 tests, Po0.05. dN = 14. eN = 16. fP-value is for differences between groups tested by Mann–Whitney U-tests, Po 0.05. gP-value is for differences between groups tested by Fisher's exact tests, P o0.05. hN = 18. iN = 17.

At pre-admission, the difference between EC and UC was not significant for LBM (50.3 ± 11.0 kg vs 46.3 ± 11.0 kg, P = 0.307), FM (29.4 ± 10.9 kg vs 32.5 ± 17.6 kg, P = 0.550) and weight (79.7 ± 15.5 kg vs 77.8 ± 21.9 kg, P = 0.770). Changes in body composition were analysed for participants who completed body composition assessment at pre-admission and 100 days post transplantation (Table 3). Overall, EC exhibited less weight and fat loss. Loss of LBM was similar between EC (−0.9 kg, CI 95% − 1.8, 0.01) and UC (−0.8 kg, CI 95% − 2.6, 1.0). Between hospital discharge and 100 days post transplantation, both groups improved in global QoL and all functioning subscales (Table 2). Unadjusted results showed that increase in global QoL favoured EC, however, adjusted results were not significantly different compared with UC. Similarly, unadjusted results for functioning subscales showed greater improvement in scores amongst EC with increase in social functioning being significant (P = 0.040); after adjustment, group differences were reduced and were not significant. Unadjusted and adjusted changes in physical activity time between hospital discharge and 100 days post transplantation were not significantly different between groups (all P>0.05, see Table 2). However, the trend showed that the mean increase in moderate activity and vigorous activity time was greater amongst UC patients, whereas mean increase in walking time was greater amongst EC patients. At 100 days post transplantation, descriptive results showed similar proportions of EC and UC patients Bone Marrow Transplantation (2014) 786 – 792

(67%, n = 10/15 vs 56%, n = 9/16) were classified as ‘sufficiently’ active for health (that is, ⩾ 150 min total activity time over ⩾ 5 sessions a week)27. With respect to the types of activity, individual data (not shown) indicated fewer EC patients (n = 4/15) than UC patients (n = 8/16) reported ⩾ 1 h moderate and vigorous activity combined per week meaning most of EC patients engaged in low-intensity activity (that is, walking). Adherence was low based on the criteria of completing at least three out of five calls for both nutrition and exercise components. Seventy-per cent of EC received at least three nutrition calls, and 70% received at least three exercise calls; however, only 47% received three or more calls in both components. No adverse event associated with the intervention was reported.

DISCUSSION This pilot study is the first to examine the use of telephonedelivered nutrition and exercise counselling as a method of ongoing supportive care when patients treated with autologous PBSC transplantation are discharged from the hospital. Results were not statistically significant after adjustment, but we observed clinically important differences in patient outcomes favouring the intervention group including fewer patients reporting nutrition impact symptoms, less weight loss, greater recovery in dietary intake and greater improvement in components of QoL. © 2014 Macmillan Publishers Limited

Nutrition and exercise after stem cell transplant Y-C Hung et al

789 Assessed for eligibility (N = 55)

Excluded (n = 18) n = 5 allogeneic transplant n = 1 treated at a different hospital n = 12 declined

Recruited and assessed at preadmission (N =37) • Completed body composition assessment (n = 33)

Randomised

Allocated to extended care (n = 18): 17

Allocated to usual care (n = 19): 18 participated as control and 1 withdrew.

participated in the intervention and 1 did not participate due to death. • Completed nutrition assessment (n = 17/17)

Assessment at hospital discharge

• Completed quality of life questionnaire (n = 17/17)

• Completed quality of life questionnaire (n = 17/18) • Completed physical activity questionnaire (n = 17/18)

• Completed physical activity questionnaire (n = 17/17)

Followed up (n = 16)

Followed up (n = 17)

• Completed nutrition assessment (n = 16/16)

• Completed nutrition assessment (n = 17)

• Completed body composition assessment (n = 13/16)

Figure 1.

• Completed nutrition assessment (n = 18/18)

Assessment at +100 days

• Completed body composition assessment (n = 10/17)

• Completed quality of life questionnaire (n = 16/16)

• Completed quality of life questionnaire (n = 16/17)

• Completed physical activity questionnaire (n = 15/16)

• Completed physical activity questionnaire (n = 16/17)

Unable to complete assessment due to relapse (n = 1).

Unable to complete assessment due to relapse (n = 1).

Flow chart of participant recruitment and data collection.

Change in the PG-SGA score was similar between the groups over the intervention period, but descriptive results showed fewer EC patients experienced nutrition impact symptoms as scored by the PG-SGA than UC at 100 days post transplantation; the distribution is consistent with higher protein intake amongst EC patients. Difference in protein intake of 14 g was clinically important after adjustment (clinically important if ⩾ 10 g28). EC may have performed better owing to the nutrition counselling. Nutrition counselling has been shown to reduce nutrition impact symptoms while improving dietary intake after cancer treatment.31 The recovery of UC patients may be disadvantaged because patients experienced more adverse treatment side effects as suggested by longer length of hospital stay and higher PG-SGA score at discharge. The difference in the PG-SGA score at discharge and length of hospital stay was adjusted in the analysis. The impact of long-term counselling requires further examination. Overall, UC lost up to 3 kg more body weight than EC. Change in body composition indicated weight loss was predominantly from significant loss of fat (P = 0.03), which was consistent with our previous findings3 and other PBSC transplantation studies.2 Loss of FM may be less concerning than LBM loss, however, acute fat loss amongst this patient group is not a favourable outcome immediately after treatment, as it suggests deprivation of nutritional reservoir. Loss of fat may be temporary. Results on adult32 and paediatric33 PBSC transplantation survivors (both ⩾ 4–6 years survival), and breast cancer survivors (⩾6 months survival)34 showed weight recovery favoured fat gain over LBM. This trend of change is not desirable as excess FM can mask a LBM © 2014 Macmillan Publishers Limited

deficit, as well as increase the risks of overweight-related health issues. Patients should be informed about the risks of excess fat gain to reinforce positive lifestyle behaviours. We did not observe a statistically significant or clinically important difference in LBM recovery amongst EC (clinically important if ⩾ 1 kg29), whereas two PBSC transplantation studies found a significant increase in LBM after 12 weeks (supervised)14 and 6 months (self-directed)15 of exercise; both had small sample sizes (n = 12 and n = 24, respectively). Inadequate resistance or high-intensity exercise may explain small improvements in LBM of our participants. Although 67% (n = 10/15) of EC participants met the recommended ⩾ 150 min exercise (level deemed sufficiently active for health),27 individual data show only one in four (n = 4/15) reported ⩾ 1 h moderate or vigorous activity per week, whereas the remaining time was composed of walking. Emphasis is needed on higher intensity exercise particularly resistance training, as aerobic exercise has shown to improve body composition (that is, decrease FM) but not LBM gain.35–37 During follow-up, a number of participants reported their barrier to resistance type exercises included nausea, persistent fatigue or weakness. Telephone-delivered exercise counselling did not increase PAL amongst the intervention group as expected. Our finding differed with a recently published study on breast- and colon cancer survivors recruited at 2–36 months following cancer treatment.38 Differences may be explained by a longer exercise intervention (10–11 calls over 16 weeks), but also, participants had more time to recover from the immediate treatment side effects. A longer intervention is needed to confirm whether the ability to perform exercise amongst autologous PBSC Bone Marrow Transplantation (2014) 786 – 792

Nutrition and exercise after stem cell transplant Y-C Hung et al

790 Table 2. Change (Δ) for nutritional status, dietary intake, quality of life parameters and physical activity, between hospital discharge and 100 days post transplantation Mean change ± s.d. Usual care N = 17 ΔPG-SGA score −13.7 ± 5.9 Δ Energy (kJ) 3143 ± 2155 Δ Protein (g) 40.1 ± 30.1 Δ Quality of life 25.0 ± 29.5d Δ Physical 23.8 ± 23.5d functioning Δ Role functioning 45.8 ± 30.7d Δ Cognitive 14.6 ± 15.9d functioning Δ Social functioning 31.3 ± 25.7d Δ Emotional 12.5 ± 23.0d functioning Δ Walking time (min) 65.3 ± 71.9d Δ Moderate exercise 73.1 ± 188.5d time (min) Δ Vigorous exercise 22.5 ± 47.3d time (min)

Mean difference (95% CI)

Extended care N = 16 −10.9 ± 5.9 3440 ± 2486c 49.2 ± 26.2c 42.2 ± 20.3 34.2 ± 20.0

P-valuea

Usual care N = 17

Extended care N = 16

0.179 0.720 0.372 0.064 0.188

− 12.1 ± 0.9 3099 ± 514 37.3 ± 6.5 32.5 ± 5.4c 27.0 ± 4.5d

− 12.4 ± 1.0 3451 ± 560c 52.0 ± 7.0c 34.4 ± 5.4 30.6 ± 4.4

Unadjusted − 2.8 − 297 − 9.1 − 17.2 − 10.4

(−7.0, 1.4) (−1992, 1398) (−29.6, 11.4) (−35.5, 1.1) (−26.2, 5.4)

Adjusted mean change ± s.e.b

59.4 ± 23.5 24.0 ± 28.5

− 13.5 (−33.3, 6.2) − 9.4 (−26.1, 7.3)

0.172 0.263

55.4 ± 5.8d 15.6 ± 4.8d

51.1 ± 5.7 22.7 ± 4.8

53.1 ± 31.7 15.6 ± 27.2

− 21.9 (−42.7, − 1.0) − 3.1 (−21.3, 15.1)

0.040 0.728

33.3 ± 7.6d 12.0 ± 4.6d

49.8 ± 7.5 16.3 ± 4.6

150.3 ± 171.9c 47.0 ± 155.1c

− 85.0 (−185.4, 15.4) 26.1 (−100.4, 152.7)

0.092 0.678

88.2 ± 30.2d 87.1 ± 47.1d

120.9 ± 31.3c 29.8 ± 49.2c

1.0 ± 39.5c

21.5 (−10.4, 53.4)

0.181

23.6 ± 11.3d

2.8 ± 11.9c

P-valueb

Mean difference (95% CI)b Adjusted 0.3 − 352 − 14.7 − 1.9 − 3.6

(−2.7, 3.3) (−2039, 1336) (−35.9, 6.5) (−18.9, 15.2) (−17.5, 10.3)

4.3 (−14.0, 22.5) − 7.2 (−22.2, 7.9)

0.847 0.671 0.165 0.824 0.599 0.634 0.337

− 16.5 (−40.3, 7.3) − 4.3 (−18.4, 9.7)

0.165 0.532

− 32.8 (−128.5, 63.0) 0.486 57.3 (−91.1, 205.7) 0.432 20.8 (−15.4, 57.0)

0.248

Abbreviations: CI = confidence interval; PG-SGA = patient-generated-subjective global assessment. aP-value is for differences between groups tested by twosample t-tests, Po0.05. bAdjusted for age, gender, diagnosis, LOS, PG-SGA score at hospital discharge and the change from pre-admission to hospital discharge. cN = 15. dN = 16.

Table 3.

Changes in body composition between pre-admission to 100 days post transplantationa

Δ Weight (kg) Δ Lean body mass (kg) Δ Fat mass (kg)

Usual care N = 10

Extended care N = 13

Mean difference (95% CI)

P-valueb

− 6.3 (−9.2, − 3.3) − 0.8 (−2.6, 1.0) − 5.4 (−8.1, − 2.7)

− 3.0 (−5.3, − 0.7) − 0.9 (−1.8, 0.0) − 2.2 (−4.0, − 0.3)

− 3.3 (−6.7, 0.2) 0.1 (−1.7, 1.8) − 3.3 (−6.2, − 0.3)

0.062 0.927 0.030

a

Values are presented and mean and 95% confidence intervals. bP-value is for differences between groups tested by two-sample t-tests. Po0.05.

transplantation patients improves at a later stage of recovery. Telephone-delivered exercise interventions may not be effective in achieving changes in PAL immediately after autologous PBSC transplantation amongst haematological cancer patients. Unexpectedly, there was similar improvement in global QoL scores. Cancer studies that reported improvement in QoL were usually accompanied by significant improvement in LBM,14,15 or significant improvement in PG-SGA or dietary intake.31,39 Metaanalysis on cancer studies40 showed higher intensity aerobic exercise was associated with higher QoL, whereas lower intensity aerobic exercise was associated with lower QoL. On the basis of the literature, our results may be explained by the nonsignificant differences observed for changes in nutritional outcomes, body composition and activity time between the groups. Although not significant, improvement in cognitive and social functioning scores favoured EC patients and the differences were clinically important.30 Better social functioning may be attributed to participation in the intervention, as well as receiving phone calls from the practitioners. The recent systematic review41 of telephone-delivered nutrition and exercise interventions suggested o15% of studies were on cancer patients. Overall, the cancer studies observed positive outcomes including improved42 or prevented10 functional decline, improvement in fitness and fatigue,43–45 diet quality42,46–48 and QoL.43,45,49 The goals of the exercise interventions were similar to our study (that is, improve exercise time, and body composition), however, goals of nutrition interventions were different because participants were long-term survivors, or in the early stage of cancer. Nutrition goals in these studies were targeted at Bone Marrow Transplantation (2014) 786 – 792

modifiable risk factors such as improving diet quality (that is, reducing fat and energy intake while increasing fruit and vegetable intake),46–48 whereas the short-term goals of our participants were aimed at stabilising nutritional deterioration and replenishing nutrition reservoirs through emphasis on high protein and high energy intake. With limited health resources, there is a growing interest in exploring cost-effective methods to deliver health care such as telephone-delivered health services. Telephone-delivered intervention may be less expensive compared with conventional faceto-face appointments,50 however, evidence of their efficacy and effectiveness has yet to be confirmed.51 The length and the intensity of past telephone interventions varied considerably between 646,47 to 1243,44 weeks and 642 to 12 months10,45 with the frequency of telephone calls ranging from weekly, fortnightly, monthly to bimonthly. Some studies used mixed methods (that is, telephone, mailed material and face-toface),10,42,45,48 whereas a minority adopted unsupervised methods alone (that is, telephone and mailed material).43,44,46,47,49 More research on telephone-delivered intervention is needed with consistent study design. To date, there is one telephone-delivered exercise intervention in PBSC transplantation cancer patients,49 but no studies on telephone-delivered nutrition intervention, or nutrition and exercise-combined intervention. Our study showed that telephone-delivered nutrition and exercise interventions were safe amongst PBSC transplantation patients immediately after hospital discharge. On the basis of adherence and safety, the intervention was feasible in 47% of the patients. Patient satisfaction of nutritional services provided in this study was © 2014 Macmillan Publishers Limited

Nutrition and exercise after stem cell transplant Y-C Hung et al

791 assessed in a sub-study; results showed EC patients were satisfied with the quality of telephone-delivered nutritional counselling.52 7

Limitations The proportion of EC patients who received three out of five calls for both nutrition and exercise components was low. Anticipated change in patient outcomes as a result of exercise may be masked because of a physically active UC group. Detailed assessment of exercise adherence is needed (that is, log book and accelerometer) in future studies; weekly reminder calls may be important for motivational purpose if counselling calls are not frequent (that is, less than once a week). Future studies may consider video calls (that is, Skype) to improve interaction between patients and practitioners but this method is limited by the availability of technologies (that is, computers). Longer interventions may be needed to achieve significant benefit. Our sample size was relatively small but this was a common limitation in trial studies amongst PBSC transplantation patients (that is, both n = 12)14,53 and other telephone-delivered lifestyle interventions (that is, sample size n = 24–32, attrition 0–46%).15,47,49 The different time points for body composition baseline assessment should be considered in the interpretation of results. CONCLUSION Following hospitalisation, autologous PBSC transplantation patients provided with telephone-delivered nutrition and exercise counselling may experience less weight loss, have better recovery in dietary intake and in certain components of QoL than patients provided with UC. Our findings are relevant to allogeneic-PBSC transplantation patients. Owing to the nature of the transplant types, allogeneic patients tend to experience more severe side effects associated with the treatment, therefore, they may have greater need for ongoing support programs similar to this study. Further exploration regarding the frequency and intensity of the number of telephone calls is required. The cost effectiveness of telephone-delivered nutrition and exercise care should be assessed in future studies.

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CONFLICT OF INTEREST The authors declare no conflict of interest.

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ACKNOWLEDGEMENTS We thank the Wesley Research Institute for funding the study, and the use of the body composition laboratory.

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