Hindawi Publishing Corporation
Evidence-Based Complementary and Alternative Medicine
Volume 2012, Article ID 450150, 9 pages
HematopoieticCellTransplant andUse of
Resultsfroma Pilot RandomizedControl Trial
Wolf E.Mehling,1,2E.AnneLown,3Christopher C.Dvorak,4Morton J. Cowan,4
BiljanaN. Horn,4ElizabethA.Dunn,4Michael Acree,1Donald I.Abrams,1,5
1Osher Center for Integrative Medicine, University of California, San Francisco, CA 94115, USA
2Department of Family and Community Medicine, University of California, San Francisco, CA 94115, USA
3Alcohol Research Group, Public Health Institute, Emeryville, CA 94608, USA
4Blood and Marrow Transplant Division, Department of Pediatrics, University of California, San Francisco, CA 94143, USA
5Department of Medicine, Hematology and Oncology, University of California, San Francisco, CA 94110, USA
6Department of Medicine, University of California, San Francisco, CA 94115, USA
Correspondence should be addressed to Wolf E. Mehling, firstname.lastname@example.org
Received 7 August 2011; Revised 5 November 2011; Accepted 13 November 2011
Academic Editor: Andrew Scholey
Copyright © 2012 Wolf E. Mehling et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
Background. Pediatric hematopoietic cell transplant (HCT) is a lifesaving treatment that often results in physical and psychological
discomfort. An acupressure-massage intervention may improve symptom management in this setting. Methods. This randomized
controlled pilot trial compared a combined massage-acupressure intervention to usual care. Children were offered three
practitioner-provided sessions per week throughout hospitalization. Parents were trained to provide additional acupressure as
needed. Symptoms were assessed using nurses’ reports and two questionnaires, the behavioral affective and somatic experiences
scale and the Peds quality of life cancer module. Results. We enrolled 23 children, ages 5 to 18. Children receiving the intervention
reported fewer days of mucositis (Hedges’ g effect size ES = 0.63), lower overall symptom burden (ES = 0.26), feeling less
tired and run-down (ES = 0.86), having fewer moderate/severe symptoms of pain, nausea, and fatigue (ES = 0.62), and less
pain (ES = 0.42). The intervention group showed trends toward increasing contentness/serenity (ES = +0.50) and decreasing
depression (ES = −0.45), but not decreased anxiety (ES = +0.42). Differences were not statistically significant. Discussion.
Feasibility of studying massage-acupressure was established in children undergoing HCT. Larger studies are needed to test the
efficacy of such interventions in reducing HCT-associated symptoms in children.
Hematopoietic cell transplant (HCT) can be a lifesaving
treatment for cancer and other disorders. Despite advances
in supportive care children suffer considerable physical and
psychological discomfort during their hospitalization for
HCT. Nonpharmacological means of symptom manage-
ment are attractive adjuncts to care given their generally
lower risk for additional side effects. However, there are
limited data on such interventions in this patient popula-
Massage, borrowed from both Western and Eastern tra-
including pain, nausea, and anxiety. Massage studies have
suggested benefits for oncology patients, [1–12] pediatric
patients [13, 14] and for HCT recipients, adult  as well
as pediatric , but the results from smaller studies of
pediatric HCT recipients were not confirmed in a larger
study . Large observational studies of massage in adult
cancer patients suggest benefits in the short and long term
 but these findings are limited by the lack of a randomized
2Evidence-Based Complementary and Alternative Medicine
Massage methods commonly used in cancer care include
Western (Swedish) and Eastern (acupressure) massage styles
this combination has not been previously studied.
Acupressure massage, the manual stimulation of specific
acupuncture points commonly used in traditional Chinese
medicine, can reduce chemotherapy-associated nausea [8,
15, 21–24], vomiting , anxiety, and fatigue [15, 26],
and its use by massage practitioners has been increased in
Europe [19, 27, 28] and the US . A Cochrane review
concluded that acupressure may be a low-cost, convenient,
easily administered intervention for chemotherapy patients
to reduce acute nausea . Acupressure massage can be
successfully taught to both patients and caregivers  and
shows benefits for postoperative nausea in children in a
meta-analysis . Western massage is effective in reducing
anxiety and pain [32, 33] mostly in the short term [34, 35],
and cumulative or long-term effects have been reported .
Caregivers of family members with cancer experience
high levels of distress [16, 37, 38], particularly mothers [39–
42]. Frequently, parents of children with cancer experience
symptoms of posttraumatic stress disorder (PTSD) [43, 44]
with related health problems . During the HCT process
parents report feeling helpless in the face of their child’s pain
and suffering [43, 44]. This helplessness is a key risk factor
the risk for posttraumatic stress symptoms  and other
adjustment problems in the child [48–50].
If parents are taught to perform massage on their
51, 52]. Parents reported improved self-efficacy in managing
their child’s symptoms, decreased anxiety, and decreased
stress when they massaged their sick children [53–55].
The aims of the present study were (a) to determine
feasibility of a practitioner-provided combined massage and
acupressure intervention for children undergoing HCT with
parent training for additional parent-provided massages
and (b) to collect preliminary data on the efficacy of
this intervention for decreasing treatment-related symptoms
such as nausea, vomiting, and pain. A secondary aim
explored whether training parent caregivers to provide mas-
sage decreased parents’ perceived stress and psychological
distress and improved their sense of self-efficacy.
We conducted a randomized, nonblinded pilot study of a
pediatric patients undergoing HCT at an academic medical
center. Imbalanced randomization (2:1) was used, stratified
by allogeneic versus autologous transplantation, with more
persons randomized to the massage/acupressure interven-
tion to allow greater assessment of the feasibility of the
intervention arm in this setting. Participants and study staff
by the university’s Human Subjects Review Committees, and
informed consent was obtained from participant’s parents,
and assent from participants over age 12. The study was
registered with clinical trials.gov NCT00843180.
2.1. Patients. At the preadmission intake visit for HCT
and their parents were invited to participate in the massage
study. Twenty-three patients consented (92% response rate).
the computer-generated intervention or usual care group
assignment. The envelopes were opened on the first day of
hospital admission after baseline assessment was completed.
2.2. Intervention. Two experienced (>10 years) professional
massage practitioners provided 20–30 minutes of semis-
tandardized and manualized combined Swedish and acu-
pressure massage three times a week in the patient’s room
over the entire duration of the hospital stay. Practitioners
utilized: (a) a semistandardized Swedish-style massage for
feet, legs and arms, and, when feasible, for back and shoulder
girdle; (b) acupressure massage used specific pain, nausea,
and calming acupressure points selected based on prior
Pericardium 6 (wrist) and Stomach 36 (below the knee) for
nausea; Triple Warmer 5 (wrist) for stress; Large Intestine
4 (hand) and Liver 3 (foot) for pain; Kidney 6 and Bladder
62 (ankle) for nausea/stress; Spleen 6 (above the ankle)
for stress. The practitioners instructed parents on how to
use acupressure on their child demonstrating point location
on the child and on the parent (for purposes of learning
the point location) and using an instruction sheet with
pictures, location descriptions, and indications for 9 selected
points. Parents were encouraged to perform additional
Control subjects received usual care: state-of-the-art
medical treatment for HCT with pharmaceutical symptom
management for pain and nausea but no massages or
acupressure. They were offered a single 20-minute massage
each for parent and child in the days before discharge and
separate $25 gift cards for child and parent after completion
of all questionnaires.
2.3. Measures. Two types of data were collected in both
groups: nurse’s daily clinical records and questionnaire
data. Questionnaires were administered to both parents and
children to assess the child’s physical and psychological
symptoms. Parents also answered questions about their own
wellbeing. Nurses’ clinical data included information for
each day on: nausea, number of vomiting episodes, pain,
and mucositis. Most were assessed at multiple points during
the day. Data were collected on days of hospital stay and
days to absolute white cell and neutrophil count greater than
500cells/mm3for 3 consecutive days.
Questionnaires were administered to children and par-
ents by the research assistant at baseline and then every two
weeks. One week after discharge from inpatient care, the
parent was interviewed over the phone. Questionnaires for
children age 5–7 used simplified response options and face
Evidence-Based Complementary and Alternative Medicine3
using the BASES and PedsQL. The behavioral affective and
somatic experiences scale (BASES) is a 22-item instrument
developed at St. Jude Children’s Research Hospital specif-
ically for the assessment of child distress during hospital-
ization for HCT. Independent subscales measure somatic
distress, compliance, mood/behavior (anxious, depressive),
interactions, and activity. Both child and parent report
BASES were used [59, 60]. To decrease patient burden, we
reduced the number of items to 18 by dropping two less
relevant subscales (compliance, interactions). The PedsQL
Cancer Module [61, 62] is a 28-item modular quality of
life measure for children with cancer. The cancer module
is appropriate for an inpatient setting and includes versions
for age groups: 5–7, 8–12, and 13–18 years old and for
parents. It includes eight independent subscales; we used
those corresponding to problems with pain (2 items), nausea
(5), procedural anxiety (3), and worry (1), thereby reducing
four items selected from the differential emotions scale (DES)
Parents were given an additional questionnaire admin-
istered at baseline and in the week following discharge
from the hospital. The questionnaire included the CES-D
 measure of depression  and the parent’s self-efficacy
scale  (PSES), which assessed self-efficacy of managing
their child’s symptoms. Posttraumatic stress symptoms were
assessed using the PTSD symptom scale  (PSS) .
2.4. Outcomes. Primary outcomes included symptoms of
fatigue, nausea, vomiting, and pain. Secondary outcomes
included mucositis and worry/anxiety. Several composite
variables were derived from the nurses’ daily clinical notes
and from parent and child questionnaire data. The primary
composite variable was derived classifying moderate-severe
symptoms using the three key symptoms of pain, nausea,
and fatigue using child self-report data from the BASES sub-
scales. A second summary measure was derived from nurses’
data and included number of days of any pain >3 (on a scale
of 1–10), any nausea, any vomiting, and any mucositis.
2.5. Analyses. Analysis of the data was performed using SAS
version 9.2. We compared baseline data between groups
to assess the success of randomization by demographic
and cancer characteristics and psychological status using
chi square statistics. Physical symptom scores measured by
questionnaire and nurses’ clinical records were compared
in intention-to-treat analyses using t-tests. Nurses’ multiple
daily electronic medical records were used for the time
period of 7 days before to 21 days after-transplant and
children’s self-report data at baseline and one week after
transplant. As the intervention in this pilot study was
provided during the children’s entire hospital stay, outcome
measures were collected during the entire hospital stay as
well in order to assess the feasibility of data collection in this
setting. However, for the purpose of providing efficacy data
oneffectsizes needed forsample-size calculationsfora larger
study, we limited the analysis of children self-report data
to a narrower period, as patients began getting discharged
Table 1: Patient characteristics.
7N (intention to treat):
Age (mean) (Range 5–18)
Congenital or acquired
Bone marrow failure
Congenital immune deficiency
before the self-report measures at 21 days were obtained.
Standardized Hedges’ g effect sizes were calculated taking
uneven group sizes into account. Psychological status was
assessed using change scores between baseline and one week
following the transplant to control for baseline psychological
Twenty-five children aged 5 to 18 years old and their
rooming-in parents were admitted for HCT at the university
children’s hospital between November 2008 and December
2009 and invited to participate; 23 consented and enrolled.
Patient characteristics are summarized in Table 1. Sixteen
children were randomly assigned to the massage group and 7
to usual care (Figure 1).
During a median hospitalization of 41 days, children in
the intervention group received a median of 8.5 massages
averaging 1.6 massages per week. Fourteen of the 16 parents
(87%) reported performing massages on their children.
Children and parents completed all requested surveys and a
postdischarge telephone survey. No adverse side effects for
the intervention were reported.
Five children were discharged from the hospital before
the 3-week posttransplant survey; thus the focus of the
data analysis is on the nurse’s daily notes and the one-
week posttransplant self-report data. This small feasibility
study was not expected to provide sufficient power to show
statistically significant differences between groups; thus we
report standardized effect sizes that allow for sample-size
calculations for future studies.
4Evidence-Based Complementary and Alternative Medicine
Randomized to massage
(n = 16)∗
Refusals (n = 2)
Eligible for HCT, age 5–18,
speaker (n = 25)
Randomized to usual care
(n = 7)
∗assessment included medical records for n = 16, but self-report data were missing on n = 1 due to a temporary
lapse of IRB approval
Figure 1: Participant flow chart.
Results for key symptoms as reported in the nurse’s daily
notes are summarized in Table 2. None of the symptoms
showed statistically significant improvements in the mas-
sage/acupressure group. However, we did find some large-
to-moderate effect sizes (ES) in favor of the intervention in
several important outcomes. Based on nurse’s data, children
in the intervention group had fewer days of mucositis
(ES = 0.63) and lower overall symptom burden (ES =
0.26). Data from the child’s self-report also did not show
statistically significant benefits for the massage group, but
showed a trend toward improved fatigue, ES
P = 0.08. In addition the intervention group reported
fewer moderate/severe symptoms in a summary measure of
fatigue, pain, and nausea (ES = 0.62) and decreased pain
(ES = 0.42). There were no statistically significant between-
group differences in duration of hospital stay or days to
Findings related to psychological outcome measures
(Tables 3(a) and 3(b)) are reported using change scores.
The intervention group showed more self-reported bene-
ficial changes for depression (ES = −0.45) and content-
ness/serenity (ES = +0.50). Sleep was reported to have
changed in a negative direction in the intervention group
(ES = −0.96); likely a spurious finding, as a worsening of
sleep as a result of our intervention does not make sense
and was not confirmed in qualitative interviews. Parental
outcomes of self-efficacy, perceived stress, posttraumatic
stress symptoms, and mood showed no differences between
groups at the time of hospital discharge.
Our results demonstrated the feasibility of providing and
studying a combined Swedish massage and acupressure in-
tervention in a pediatric HCT unit. While the sample
size was small, the data suggested some efficacy of the
massage/acupressure intervention, particularly related to a
reduction in days with mucositis, improvements in fatigue,
and reduced pain and loss of appetite. Use of daily nurse’s
clinical data combined with biweekly self-report data from
both children and parents provided multiple perspectives on
the clinical efficacy of the intervention for our key outcomes.
While the effect sizes we observed are encouraging, the
results must be interpreted cautiously given the small sample
size and lack of statistically significant differences between
groups. A larger study would be needed to determine
whether the effect sizes suggested in this pilot study can be
confirmed with statistically significant results. Based on our
results for a key study outcome—the summary score of the
three key symptoms of pain, nausea, and fatigue (ES = 0.62),
the study would have required at least 64 participants in each
group to show a statistically significant difference.
The feasibility of the study was further supported by
enthusiastic qualitative data obtained from parent interviews
and nurses’ reports. These findings are reported separately in
There are a number of unique aspects of the present pilot
study compared to other studies in the field of massage and
pediatric oncology. The present pilot tested an integration
of Eastern and Western massage styles, as is increasingly
practiced in the United States. The potential benefits include
the relaxing aspects of Swedish massage [1, 33] combined
with the potential efficacy of acupoint therapy for pain,
nausea, and other symptom relief . To our knowledge,
there are no comparable studies that have tested an inte-
gration of Eastern and Western massage. Involvement of
parents in providing additional nonprofessional massages
is another innovative feature of our intervention with the
Evidence-Based Complementary and Alternative Medicine5
(a) Symptoms from the nurses records over 29 days (7 days before to 21 days after transplant). Intervention (I; N = 16) versus control (C; N = 7).
Symptom (scale range)Arm
(Days until 3 days of WBC > 500)C
Days with high symptom burden (pain
> 3, nausea, mucositis, and vomiting)1
Days of pain > 3 (on 0–10 scale)
Days of vomiting
Days of mucositis
(b) Symptoms from child self-report: at baseline and 1 week after transplant. Intervention (I; N = 15) versus control (C; N = 7).
Symptom (scale range)
Nausea and vomiting1(0–4)
Loss of appetite1(0–4)
Feeling tired/run down1(0–4)
Summary score of 3 moderate/severe
symptoms of fatigue, pain, and
1Higher score: worse symptoms.
∗ES: standardized effect sizes (“+” ES is advantage for intervention; “−” ES is advantage for control).
SD: standard deviation.
∗∗Sum of moderate or severe (“quite a bit/very much” versus “none/a little/somewhat”) symptoms of fatigue, nausea, and pain, 1 week self-report
(range: 0–3 symptoms).
All measures were from the BASES questionnaire except pain was measured using the Peds quality of life scale.
added benefits of increasing the massage dose, supporting
timely symptom management and enabling parents to help
their children directly.
A previous single-site pilot study performed by Phipps
and colleagues  demonstrated promising results in
improved symptom management, but these results were not
confirmed in a larger multisite study . The intervention
used in this larger study, a combination of a laugh cart,
a guided relaxation and Western massage was substantially
different from the present study, with most overlap in the
shared aim of reducing child discomfort by nonpharmaco-
logical means. The present study may have benefited from
the additional use of acupressure, which may account for the
moderate-to-high effect sizes for some symptoms compared
to this prior study.
Another small feasibility study in 17 children with cancer
who were undergoing chemotherapy used a crossover design
in which 4 weekly massage sessions alternated with 4 weekly
quiet-time control session. This study found that massage
was more effective than quiet time at reducing heart rate
and anxiety in children less than 14 years but did not show
improvements in pain, nausea, or fatigue . The authors
concluded that massage in children with cancer is feasible
and appears to decrease anxiety. The present study also
showed feasibility, but otherwise found different results with
moderate ES for a decrease in pain and fatigue and less
improved anxiety in the intervention group compared to
controls. The addition of acupressure in the present study
study, but sample sizes are small in both studies.
Finally, a randomized feasibility study of acupressure in
preventing chemotherapy-associated nausea by Jones and
colleagues was conducted among 21 pediatric oncology
patients, ages 5 to 19 years, using wrist bands compared to
placebo bands . Acupressure applied using wrist bands
was feasible and well tolerated but there were not statistically
significant results compared to placebo, potentially due to
small sample size. While Jones’s study used a bead to apply
6Evidence-Based Complementary and Alternative Medicine
(a) Changes in negative affect from baseline to 1 week after transplant. Mean “+” change indicates worsening; mean “−” change indicates improvement;
ES “−” indicates benefit for intervention compared with control; ES “+” vice versa.
by child reportC0.7 ±0.8
by child reportC1.4 ±1.1
by child reportC1.7 ±1.4
by parent reportC2.0 ±1.5
(b) Changes in positive affect and sleep quality from baseline to 1 week after transplant. Mean “+” change indicates improving; mean “−” change
indicates worsening; ES “+” indicates benefit for intervention compared with control; ES “−” vice versa.
by child reportC2.1 ±1.3
by child reportC2.9 ±0.7
by child reportC2.3 ±1.0
1Higher score: worse negative affect.
2Higher score: higher positive affect.
3Higher score: better sleep.
∗ES: standardized effect sizes.
I: intervention, C: control.
SD: Standard Deviation.
(Sample N for intervention (I) versus control (C); intention to treat: 15 versus 7).
Symptom change (scale range)
Symptom change (scale range)
pressure on one acupoint, it differed from the present
study, in which acupressure was provided by experienced
practitioners who used multiple points.
The finding that the intervention may have reduced
days with mucositis and reduced tiredness, although at first
surprising, may in fact reflect a potential mechanism of
action that has been suggested by results from prior acupoint
studies, namely, a reduction in proinflammatory cytokines
such as TNF-α, IL-1, and IL-6 . These proinflammatory
cytokines are increased during chemotherapy, probably due
to high levels of apoptosis (programmed cell death). Some of
these proinflammatory cytokines, in turn, are hypothesized
to be important factors in chemotherapy-related fatigue
 and mucositis . This hypothetical mechanism may
deserve further investigation in a larger trial with the
addition of biological samples.
The present study focused on longer-term changes in
symptoms (assessed every other week from self-report or
daily by the nurses) rather than short-term changes (minutes
or hours) after the intervention. This design allowed us to
assess only the more enduring effects of massage, but not the
immediate effects. Future studies might benefit from both
short- and longer-term assessments. Short-term benefits
from massage have been reported in other studies  and
appear to be more consistent than longer-term effects.
Limitations of this feasibility study include the small
sample size and the limited number of time points for self-
report assessments. In addition, the dose of the massage
of scheduling difficulties related to periods of time with
severe symptoms, unscheduled naps, and high health care
demands. Participants often preferred massage sessions in
providers had limited evening availability. Finite resources
made it difficult to ensure wider availability of the massage
provider. Based on our results, we believe that an increased
dose of massage would be facilitated by having a provider
regularly available during the late afternoon and evening for
several hours per day (rather than individually scheduled
Major strengths of the study include the feasibility and
acceptability of a massage/acupressure study on a busy
pediatric stem cell transplant unit, indications of efficacy of
the intervention, the lack of side effects, and the enthusiastic
support for the intervention by the involved pediatricians,
nurses, and parents [68, 69].
Swedish massage and acupressure for improved symptom
management in children undergoing hematopoietic cell
Evidence-Based Complementary and Alternative Medicine7
transplants. Findings from this and larger future studies have
the potential to influence clinical practice related to stem cell
transplant-associated symptoms in children by introducing
massage and acupressure, an ancient healing modality,
into a “high-tech” pediatric hospital setting. Massage and
acupressure for symptom management are attractive, given
their potential to treat multiple symptoms with few or no
side effects. Future studies should enroll sufficient numbers
to better test the efficacy of combined Swedish massage
and acupressure in symptom management of pediatric
hematopoietic stem cell transplant.
The authors thank the children and parents who took
part in this study; the Community Foundation Sonoma
County, Santa Rosa California that sponsored the study;
massage/acupressure practitioners Marcia Degelman, Paula
Koepke, and Jnani Chapman; research assistants Kristina
Kavanau, Viranjini Gopisetty, and Derek Ramsey; the nurses
on the children’s hospital’s transplant unit with Trish Mur-
phy and Sara Okane as nurse coordinators. Wolf E. Mehling
and E. Anne Lown contributed equally to this paper.
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