COMPLEMENTARY THERAPY FOR CHILDREN WALKING PUNCA CELL

TRANSPLANTATION

First published: July 12, 2010Full publication history

DOI: 10.1002 / cncr.25415 View / save quote

Quoted by (CrossRef): 19 articlesCheck for updates

ABSTRACT

BACKGROUND:

Children who undergo stem cell transplant (SCT) have somatic disorder and high mood
disorder. These trials evaluate the efficacy of complementary therapies (massage, humor
therapy, relaxation / image) to reduce the pressure associated with childhood SCT.

METHOD:

In 4 locations, 178 pediatric patients scheduled for SCT were randomized to intervention-
intervention interventions involving massage and humor therapy, identical child interventions
plus parental interventions involving massage and relaxation / image, or standard care.
Randomization is grouped by site, age, and type of transplant. Interventions start at entry and
continue through SCT Week +3. Key outcomes include patient and parent reports of somatic
disorders and mood disorders gained each week from entry through Week + 6 using the
Behavioral, Affective, and Somatic Scale. Secondary outcomes include length of stay, time for
engraftment, and use of narcotic analgesic and antiemetic drugs.

RESULTS:

A mixed model approach is used to assess longitudinal trends in patient and parent outcomes
and to examine group differences in these measures. Significant changes over time were
observed in all patient and parent outcomes. However, there were no significant differences
between treatment weapons found in the primary outcome. Similarly, no significant intergroup
differences were recorded in any of the medical variables as a secondary outcome.
CONCLUSION:

The results of this multisite trial failed to document the benefits of significant complementary
interventions in the setting of children's SCT. Cancer 2010. © 2010 American Cancer Society

The use of hematopoietic stem cell transplantation (SCT) for the treatment of childhood
malignancy and other serious pediatric disorders poses a unique challenge for patients and their
families.1,2 Despite advances in supportive care, SCT remains a high-risk medical procedure,
involving the Regimen Prolonged and physically demanding treatment that can create high
levels of stress, and may cause further adjustment difficulties

Survivors.3-8 Previous studies on the history of patient adjustment during the acute phase of
SCT indicate that the patient continues to experience high levels of somatic pressure and
associated mood disorders during the acute phase of SCT.9,10 Furthermore, Parenting
caregivers also experience high emotional distress in The same time frame.11,12 Patients 'and
parents' difficulties seem relatively temporary, peaking in the early weeks after transplantation
and returning to baseline at baseline within 4 to 6 months post-SCT.9-12 However, Which is
so unacceptable that survives despite aggressive and sophisticated supportive care, indicates
the need for the development of new interventions for stress reduction.

Several intervention trials on adult SCT settings have involved complementary therapies. The
Mind-Body approach, including hypnotic, and relaxation / imagery trials has shown benefits
in relieving pain, nausea, and analgesic use.13,14 Interventions of massage therapy with adults
undergoing autologous SCT show a significant rapid decline in fatigue, nausea , And anxiety
relative to control, but the effect is not maintained.15 In other randomized trials in adults
undergoing SCT, patients receiving massage and therapeutic contacts reported greater overall
comfort and benefits than comparable cohorts with friendly visits, but none Differences
between Groups in time for engraftment scores or toxicities.16 Others

A complementary approach that has been tested in adult SCT settings is music therapy.17
Adults who underwent SCT who underwent music therapy during inpatient admissions
reported lower levels of mood disorder than controls. Similar findings were found in tests of
music therapy with children with cancer during hospitalization

We conducted a pilot study demonstrating the feasibility of complementary interventions in

the regulation of SCT, which exposed the patient to several stress reduction techniques
including: 1) relaxation exercises, using image usage; 2) massage therapy, taught and given by
 parents; 3) humor therapy; And 4) emotional expression therapy.19 Eligibility is demonstrated,
and overall intervention is assessed to be helpful or better by 85% of patients and parents. In
addition, a clear pattern is observed regarding individual components, which indicate that
massage and humor therapy is rated higher than yes

Table 1. Demographic and Medical Background

Characteristic No. %

SD indicates standard deviation; HSC, Hospital for Sick Children; CHOP, Children's Hospital of
Philadelphia; NCH, National Children's Hospital; Allo, allogeneic; ALL, acute lymphoblastic leukemia;
AML, acute myelogenous leukemia; HD, Hodgkin's disease; NHL, non-Hodgkin's lymphoma.

Age, y (mean, 12.8; SD, 3.9)

6-12 84 49.1

>12 87 50.9

Male sex 101 59.1

Race/ethnicity

White 121 70.7

Black 26 15.2

Hispanic 8 4.7
Characteristic No. %

Asian 7 4.1

Other/unknown 9 5.3

Socioeconomic status

I 28 16.4

II 60 35.1

III 35 20.5

IV and V 27 15.8

Unknown 21 12.3

Resident parent

Mother 141 82.4

Father 20 11.7

Other 10 5.8

Site

St. Jude 71 41.5

Characteristic No. %

HSC-Toronto 41 23.9

CHOP 35 20.5

NCH-Columbus 24 14.0

Type of transplantation

Autologous 31 18.1

Allo-matched sibling 44 25.7

Allo-other 96 56.1

Diagnostic group

ALL 46 26.9

AML 42 24.6

Other leukemia 23 13.5

HD/NHL 18 10.6

Solid tumor 21 12.3

Nonmalignancy 19 11.1
DESIGN AND PROCEDURES

Patients were recruited before admission to SCT, and informed consent and child consent were
obtained from all participants. Patients and parents complete the basic steps before
randomization. Randomization is grouped by location, age (6-12 years,> 12 years), and type of
transplantation (autologous, allogeneic-match, allogeneic-other). Interventions begin on entry,
and proceed through SCT Week + 3. The primary outcome is the self-report of the patient and
the parents are obtained weekly for 8 observations from reception (Sunday -1) to Week 6.
Secondary outcomes include medical variables derived from chart reviews, and long-term self-
run report results obtained at 12 and 24 weeks.

BEHAVIOR, AFFECTIVE, AND SOMATICAL SCALE (BASES)

BASES35, 36 provides an acute aspect assessment of health-related quality of life for pediatric
patients receiving aggressive care. This instrument is designed for repeated use and sensitivity
to change, and scores on 5 subscale scales, labeled Somatic Distress, Mood Disturbance,
Compliance, Quality of Interactions, and Activity.35 The initial scale contains 38 items, but
then shortened to 22 items. , Without loss of reliability.21 Versions of parent, child, and nurse
reports are available that contain the exact item content. BASES data are obtained from parents
and patients every week since transplant entry until 6 weeks after SCT.

POSITIVE AND NEGATIVE SCHEDULE FOR CHILDREN

Because BASES focuses solely on distress, Positive and Negative Affects the Schedule for
Children (HOT-C) 37 is added to give a measure of positive influence. We used a modified
version of the HOT-C scale described by Crook et al. 37 using only positive impact items, of
which 4 items were added - calm, relaxed, comfortable, and peaceful - reflecting the expected
effects of our interventions. This scale is obtained on the same schedule as BASES.

Medical Variable

Medical variables include: hospital day, time for engraftment, drug use, and specific toxicity.
Days in the hospital were measured using the number of days from transplant to first hospital
discharge, and also assessed the number of hospitalized days through the Moon +3 (Day 90).
The time for engraftment was assessed by taking the number of days until the patient obtained
absolute neutrophil count> 500 for 3 consecutive days. Two measures of drug use were
obtained: the use of analgesics and narcotics. All narcotics released through Day +21 are
recorded, and the total dose of each agent is changed to the equivalent of morphine. The dose
of all the agents is combined and divided by the patient's body weight at admission to give a
single index in milligrams per kilogram of morphine equivalent. All antiemetics are recorded
from reception through Day +21. Because of the large number of agents used, and the
difference in standard procedures for prophylactic treatment at all sites, we record the number
of days in which unscheduled antiemetics are distributed. So, there is one score, which shows
the number of days where unscheduled antiemetics are shared via Day +21. To assess toxicity,
we used National Cancer Institute poisoning ratings obtained routinely in all locations, and
applied a summary scale developed by Bearman and colleagues.38 Toxicity values were
calculated on Week +3.

INTERVENTION

Standardization of interventions is facilitated by the use of written manuals and electronic

media. The massage routine is manualized, and a DVD showing the massage routine is
developed and circulated to a massage therapist all over the place. All massage therapists are
licensed in their state or province. CD relaxation and imaging procedures developed
specifically for this study, and distributed to all participating parents. Relaxation and humor
interventions were performed by research assistants after a 2-day centralized training.

INTERVENTION OF CHILDREN

Children who are randomized to receive interventions are informed of the benefits of massage
and humor. Age-appropriate handouts reinforce the benefits of taking a massage and a pause
of humor. Patients and parents meet with a licensed massage therapist upon admission to
introduce them on the reason of a massage intervention before giving an initial massage
session. The ½ hour massage sessions are scheduled 3 × per week from entry through Week
+3. For humorous intervention, each site develops a humor cart full of shorts, books, jokes, and
more. Interventions focus on 3 procedures: 1) education on laughter and laughter regularly; 2)
easy access to humor material through humor carts; And 3) continue to give encouragement in
the use of humorous material by therapist research assistants who meet with patients every
week.

THE INTERVENTION OF PARENTS

Parental interventions begin by educating parents about the benefits to their children resulting
from improving their own wellbeing. Parental massage interventions are identical to the child,
with session 3

STATISTIC ANALYSIS

The main results consist of BASES by patient and parent reports, and HOT-C. Given the
complexity of comparing groups across repetitive actions, 2 inferential approaches are used.
First, we compare the differential region under the curve from Week 1 to Week +3 after
subtracting Week -1 value. This allows a single estimate of overall treatment effects during the
intervention period. Second, to better appreciate the longitudinal trend, the mixed model
approach is used to assess changes over time regarding these steps. This trend (curve) is
estimated using a polynomial function, in which week is the number of weeks from SCT (ie,
linear trend), week 2 for quadratic effect, week3 for cubic effect, etc., using SAS Proc Mixed.39
Initially, we Examining group differences for all BASES subscales of somatic pressure, mood
disorders, compliance, interaction quality, activity, and sleep. Because this subscale is highly
interlinked, we examine BASES data as a single scale that combines all subscales, to reduce
experiment errors and make findings easier to interpret. This reduces BASIC outcomes into 2
variables; Combined BASIS scores based on patient reports and parent reports. For secondary
outcomes from length of stay in the hospital, time for engraftment, and drug use, group
differences were examined using the Kruskal-Wallace test.

RESULTS

Intervention Compliance

The number of massage sessions given is used as a learning compliance indicator. With the
expected dose of 12 massage sessions (3 / week × 4 weeks), the average number of massages
per patient was 8.8 (standard deviation [SD], 3.1, median, 10), while for slightly older parents
Low, with an average of 7.6 (SD, 3.2, median, 8). Thus, about 75% of the planned interventions
are given. Unanswered sessions are usually passively denied or missed for logistical reasons,
with a small number of active refusals. Another indicator of compliance studies is the number
of self-report observations obtained. The number of successful observations in each arm during
the study is presented in Table 2. Overall, 73% of all observations are likely to be obtained
from acceptance through Week 6, and levels remained fairly consistent throughout the study
period. This rate is comparable to that obtained in previous natural history studies.12
 Table 2. Number of Observations Per Study Arm

Table 2. Number of Observations Per Study Arm

Week HPI-C HPI-CP Standard Care Total

1. HPI-C indicates child-targeted health promotion intervention; HPI-CP, combination of parent-targeted and child-
targeted health promotion interventions.

Week −1 45 40 30 115

Week 0 48 46 42 136

Week +1 46 53 39 138

Week +2 43 42 34 119

Week +3 46 45 39 130

Week +4 39 47 38 124

Week +5 40 40 37 117

Week +6 37 42 37 116

Total Week −1 to +6 344 355 296 995

Week +12 38 44 34 116

Week +24 33 40 25 98
Week HPI-C HPI-CP Standard Care Total

Total 415 439 355 1209

PRIMARY RESULTS

The differential area under the curve for Week -1 through Week + 3 for Total BASES score
based on child report showed no significant difference in treatment group (F2,109 = 0.1; P =
.95). All 3 groups showed a slight increase in total pressure across this time frame, and all
paired contrast was insignificant. Similarly for the Total BASES score based on the parent
report, there was no difference between the groups (F2, 109 = 1.1, P = 0.35), and all paired
contrast was not significant. Finally, the impact of the intervention on positive impacts is
checked using HOT-C. Again, no group differences were found (F2,117 = 1.0; P = .36), and
no significant pairwise comparisons.

To test the longitudinal trend on the Behavioral, Affective, and Somatic Scale, the model was
installed for each of the 3 intervention arms (targeted children, targeted children, and parents,
and standard care). Longitudinal trends include linear effects as well as polynomial time
functions, including squares (time2) and cubic (time 3). Throughout the group, a clear
longitudinal trend was observed in the Behavioral, Affective, and Somatic Scores of Behavioral
Behavior based on child reports, with significant linear (P <.01), quadratic (P <.001), and cubic
(P <.01) effects . However, Reflecting the area under the curve ratio, no significant intergroup
differences were observed. The main effect examination for the treatment group showed no
difference (type III P value> .8). By using standard care as a reference group, no targeted child
(t = 0.36; P> .7) or targeted child- and parent (t = -0.21; P>, 8) is different from the control
group Based on reported patients. Likewise, there are no intergroup differences in change over
time, including linear, quadratic, or cubic (all type III P-value> .5). This may be most
appreciated graphically, as illustrated in Figure 2 (Top). The longitudinal trends of the 3 groups
are very similar. Likewise, according to parent reports, significant linear, quadratic and cubic
trends are seen (all P <.001), but again there is no significant group difference (type III P-
value> .4). Both the target group of children (t = 0.97, P> .3) and the target group of children
and parents (t = 1.3, P = .18) differed significantly from the standard care group. The
examination of longitudinal effects also revealed no group differences for linear, quadratic or
cubic (all P> .4) trends. This is graphically depicted in Figure 2 (Below).

Distress trajectory from admission through stem cell transplantation at week 6 by the
intervention arm is shown. (Top) Total Behavioral, Affective, and Somatic Behavioral
Behavior Scores (BASES) are shown by child reports. (Bottom) Total BASES distress score
indicated by parent report. HPI-C shows targeted health promotion interventions by children;
HPI-CP, a combination of health promotion interventions targeted by parents and children; SC,
standard treatment.

In HOT-C, significant longitudinal trends across the groups were observed, with linear,
quadratic, and cubic effects (all P <.001). Significant group differences were found for overall
major effects (type III P <.05). With the standard of care as a reference, there was no difference
between the standard care group and children and parents (t = -0.99; P> .3), but there was a
significant difference between the target group of children and the standard care group. (T = -
2.9, P <.01), indicating a low overall positive impact on the target group of children. This is
different from the findings that use the area under the curve, but the difference is explained
entirely by a fundamental difference, since there is no intergroup differences in linear, squared,
or cubic linear longitudinal trends (all P> .5). Again, this is most appreciated graphically
(Figure 3).

Positive affects the trajectory (Positive and Negative Influence Schedule [Hot] total score) is
indicated from entry through stem cell transplant at 6th week by intervention arm. HPI-C shows
targeted health promotion interventions by children; HPI-CP, a combination of health
promotion interventions targeted by parents and children; SC, standard treatment.

Medical results

Results for hospital length and time for engraftment are presented in Table 3. Given the skewed
nature of this data, group differences were assessed by 1-way variant analysis using the
Kruskal-Wallis test. There was no difference between groups observed for days in hospital (P>
.4) or time for engraftment (P> .3). Likewise, there is no difference between groups that are
significant for the use of narcotic analgesics (P> .8) or antiemetics (P> .5).

Table 3. Results of Hospital Duration and Time of Engraftment

Hospital Stay, d Time to Engraftment, d

Group

Mean Median Range Mean Median Range

1. HPI-C indicates child-targeted health promotion intervention; HPI-CP, combination of parent-

targeted and child-targeted health promotion interventions; SC, standard care.

HPI-C 31.1 26.0 12-131 18.5 16.0 11-40

HPI-CP 34.7 26.0 14-180 20.0 19.5 10-38

SC 30.6 23.0 11-130 19.8 19.0 10-92

DISCUSSION

The current study examined a multisite trial of complementary therapies designed to reduce
stress and improve health in children with SCT. Contrary to the hypothesis, trials produce many
incorrect findings, and there is no clear evidence of benefits for child-targeted interventions
alone, or in combination with targeted parental interventions. In the primary outcome of
somatic disorders of patients and parents, mood disorders, and activity levels as captured in
BASES, there was no difference in mean relative pressure to baseline (area under the curve)
and longitudinal trajectory of 3 groups Very similar to Effects only Were significantly less
visible for a positive impact, in which child-targeted intervention groups reported lower overall
positive impact levels during the study period compared with the standard care group or
children and the elderly. However, this is mainly due to differences at the outset, since there is
no difference in patterns in longitudinal trends. Regarding medical results, no significant
intervention effects were observed in length of hospitalization, time for engraftment, or use of
analgesic or antiemetic drugs.

This study was designed to detect a difference of 0.45 SD between the standard care group and
the intervention group (target children or children- and parents) in areas below the average
curve value at BASES from week 1 to week 3, On Α = 0.05 with 80% power. Because the
samples were rather small at the time of study entry and a further reduction in sample size of
the lost data, the power was reduced so that there was an 80% power to detect a 0.55 SD effect
size, which is generally regarded as a moderate effect. Thus, it is possible that the null findings
reflect a lack of sufficient strength to detect smaller group differences. Descriptively, the
observed effect is quite small, with the effect size between the standard care group and the
target group of children 0.05 in the BASES child report; 0.07 on BASES parent report, and -
0.22 in HE-C. Similarly, the effect size for comparison between the standard care group and
children and the elderly was 0.04 for the BASES child report, 0.24 for the BASES parent report,
and -0.15 in H-C. This effect is so large that we do not consider it to be clinically relevant.

The absence of significant intervention effects is disappointing and somewhat surprising, given
previous studies on complementary therapies in adult transplantation settings, as well as our
own pilot study.16-21
This forces the examination of factors that might lead to a lack of the effects of these
interventions. One problem is whether the most appropriate measure of outcome has been
assessed. It was an anecdotal impression from the study staff, based on observations and reports
of patients / parents, that those who received the intervention experienced benefits. However,
when objective, repetitive action is obtained, there is no evidence of visible benefits. Of course,
it is possible that there are relevant results that are not measured, but BASES was developed
specifically for the purpose of measuring transplant-related disorders, and proven to be
sensitive to changes over time in this study. Thus, the null findings can not be attributed to the
measurement insensitivity. In addition, the absence of group differences in day-to-day medical
outcomes in hospitals, the time for engraftment, and drug use are consistent with our unhelpful
findings of the report's own results, and show that the intervention did not produce the desired
effect.

Our measurement time is another potential issue. In many previous studies on complementary
therapies, particularly massage, action has been obtained before and after postmen- natal
interventions.16-19, 22-25 The direct effects of massage in reducing anxiety and pain reports
are well established.22,25 However, these effects appear to be relatively mature Short, and may
not reflect the effects of ongoing interventions, as well as the cumulative effects of recurrent
interventions during transplantation hospital admission, which is our primary focus. The
current findings do not show any significant intervention intervention effects. Perceptions of
patients and parents about benefits may not reflect actual positive changes, a trend that has
been found previously with massage in transplant settings.40

Another factor that may contribute to the null findings is a relatively low degree of difficulty
in the overall sample. Although there is a clear longitudinal trend observed, with a peak in
distress of about 1 week, as reported in previous natural history studies, 9, 10 absolute pressure
levels are very low, and the amplitude of change from entry level to peak level is smaller than
the report previous. Probably a fix