Benefits of Intrahospital Exercise Training After

7/30/2019 Benefits of Intrahospital Exercise Training After

1/8

Introduction!

Bone marrow transplantation (BMT) following a

high dose of chemotherapy is a potentially cura-

tive treatment for patients with severe hemato-

logical disorders, e.g., leukemia. This therapeutic

tool is, however, associated with several trans-

plant-related toxicities (particularly, altered car-

diorespiratory function) which compromise full

rehabilitation and result in early fatigue during

physical activities of daily living and decreased

quality of life (QOL) [3]. In survivors of childhood

leukemia, BMT is associated with marked de-

creases in peak oxygen uptake (VO2peak), a widely

accepted index of functional capacity, health sta-

tus and survival rate [20].

Previous reports have shown the benefits of exer-

cise training in the physical capacity and overall

health status of adults who have undergone BMT

[5,7 9,29]. Considerably less research efforts

have focused on pediatric populations receiving

the same medical treatment. We recently re-

ported positive results on very young children

( 7 years) in the last phase of treatment against

leukemia (without BMT) who performed a super-

vised, intrahospital training program combining

resistance and aerobic exercises [37, 38]. How-

ever, no study has specifically assessed the car-

diopulmonary and neuromuscular effects of this

type of intervention in children receiving BMT

for leukemia treatment.

It was therefore the purpose of the present study

to determine if an 8-week intrahospital super-

vised, conditioning program including both re-

sistance and aerobic training improves func-

tional capacity (e.g., VO2peak), dynamic muscular

strength of the upper and lower extremities,

muscle functional mobility, ankle range of mo-

tion, and QOL in children who have undergone

BMT within the previous 12 months for the treat-

ment of leukemia. Based on the results of recent

research on adult cancer survivors [17] and pa-

tients with pediatric cancer [37,38] and what is

known to occur in healthy children [1113,32],

we hypothesized that this type of program would

have beneficial results and thus would be of clin-

ical relevance.

Abstract!

The purpose of this study was to determine if an

eight-week intrahospital supervised, condition-

ing program improves functional capacity and

quality of life (QOL) in children (4 boys, 4 girls)

(mean [SD] age: 10.9 [2.8] years [range: 816])

who have undergone bone marrow transplanta-

tion (BMT) for leukemia treatment within the

last 12 months. A group of 8 age and gender-

matched healthy children served as controls. The

experimental group performed 3 weekly sessions

of resistance and aerobic training inside an intra-

hospital gymnasium. A significant combined ef-

fect of group and time (p < 0.05) was observed

for muscle functional capacity (Timed Up and

Down Stairs [TUDS] test) and peak oxygen uptake

(VO2peak

), i.e., with BMTchildren showing greater

improvements than controls (VO2peak at pre- and

post-training of 25.9 (8.2) and 31.1 (7.6) mL/kg/

min in diseased children). Muscle strength (6

RM test for bench and leg press and seated row)

also improved after training (p < 0.05) in the

BMT group. Concerning QOL, a significant com-

bined effect of group and time (p < 0.05) was also

observed for childrens self-report of comfort and

resilience and for parents report of their chil-

drens satisfaction and achievement. In sum-

mary, children who have received BMT experi-

ence physical and overall health benefits after a

relatively short-term (8 weeks) supervised exer-

cise training program.

Benefits of Intrahospital Exercise Training afterPediatric Bone Marrow Transplantation

Authors A. F. San Juan1, C. Chamorro-Via 1, S. Moral 1, M. Fernndez del Valle1, L. Madero 2, M. Ramrez2, M. Prez 1, A. Lucia 1

Affiliations 1 Department of Physiology, Universidad Europea de Madrid, Madrid, Spain2 Department of Hematology and Bone Marrow Transplantation, Childrens Hospital Nio Jess, Madrid, Spain

Key words

l" cancer

l" children

l" quality of life

l" graft-versus-host disease

l" resistance training

l" VO2peak

accepted after revision

May 27, 2007

BibliographyDOI 10.1055/s-2007-965571

Published online Oct. 25, 2007

Int J Sports Med 2008; 29:

439 446 Georg Thieme

Verlag KG Stuttgart New York

ISSN 0172-4622

CorrespondenceProf. Alejandro LuciaDepartment of PhysiologyUniversidad Europea de MadridVillaviciosa de Odn28670 MadridSpainPhone: + 34916 647800Fax: + 349 [email protected]

439

San Juan AF et al. Pediatric Bone Marrow Transplantation and Exercise Int J Sports Med 2008; 29: 439 446

Clinical Sciences


2/8

Material andMethods!

PatientsBefore entering the study, informed consent was obtained from

each participants parents and the study was approved by the lo-

cal Human Investigations Committee and Review Board. A pre-

liminary screening for subject selection was performed in the

medical database of the Onco-Hematology Department at Chil-

drens Hospital Universitario Nio Jess (Madrid, Spain). A totalof 40 medical records of children survivors of leukemia who had

undergone BMT in the aforementioned hospital were examined.

After the oncologist treating each patient provided consent, sub-

jects were deemed eligible for the study if they met each of the

following conditions: 1) survivors of childhood leukemia with

time elapsed after BMT 12 months; 2) 8 16 yrs of age; 3) hav-

ing no condition that could contraindicate vigorous physical

activity, such as severe anaemia (hemoglobin < 8 g/dL), fever

> 38 8C, or severe cachexia (loss of > 35% premorbid body mass),

platelet count lower than 50 109/L, neutrophil count lower

than 0.5 109/L or anthracycline-induced cardiotoxicity [23];

4) currently living with their parents in Madrid (Spain); and 5)

having not participated in any type of exercise training program

prior to the study.

Eight children (4 boys, 4 girls; age: 10.9 2.8 [mean SD] years;

height: 135.5 25.6 cm; time post-transplantation: 8.9 4.5

months [range: 212]) met all the abovementioned eligibility

criteria and were included in the study. Their Tanners stage of

maturation was I (n = 3), II (n = 3), III (n = 1) and IV (n = 1). Four

children were survivors of acute lymphoblastic leukemia and

four of acute myeloid leukemia. They had received haploidenti-

cal (n = 4) or allogeneic BMT (n = 4). Children with allogeneic

BMT received daily immunosuppressive therapy (corticosteroids

[6-metil-prednisolone] in three patients and mycophenolate in

one patient) throughout the entire training period (see below)

for the treatment of graft-versus-host disease. The latter is a

multiorgan inflammation (e.g., scleroderma, esophagitis, biliary

cirrhosis, sicca syndrome, polymyositis) that develops after allo-

geneic BMT [39]. One girl was also receiving treatment against

osteopenia (calcium + estrogens).

A group of eight, nonathletic healthy children matched for age

and gender (4 boys, 4 girls; age: 10.9 2.6 years; height:

138.8 16.4 cm) were selected as study controls. All lived with

their parents in Madrid and had a socioeconomic status similar

to the BMT group, i.e., they lived in the same part (~ 400 000 in-

habitants) of Madrid (total population of 3.2 million).

Study protocolThe patients performed the same battery of tests (treadmill ex-

ercise, muscular strength [6 RM], functional mobility, passive

and dynamic ankle range of motion and QOL questionnaires) be-

fore and after the exercise training program that is described be-

low. For ethical and logistic reasons (particularly, long duration

of the familiarization period inside an intrahospital setting),

healthy controls only performed the tests in the Exercise Physi-

ology Laboratory outside the Hospital (see below).

SettingAn intrahospitalgymnasiumdesignedto be used by children dur-

ing anticancer treatment (Childrens Hospital Nio Jess of Ma-

drid, Department of Onco-Hematology and Bone Marrow Trans-

plantation) [23] wasthe site where all training sessions, dynamic

strength tests and Time Up and Go 3-m and 10-m tests were per-

formed (see below). Among other equipment, the intra-hospital

gymnasiumincludes pediatric(specifically built forthe body size

of children) weight training machines (Strive Inc., Canonsburg,

PA, USA) and bicycle ergometers (Rhyno Magnetic H490, BH Fit-

ness Proaction, Vitoria, Spain).

Treadmill tests, Timed Up and Down Stairs test and evaluation of

passive and dynamic ankle range of motion (see below) were

performed by all participants (patients + controls) in a Univer-

sity setting outside the Hospital (Exercise Physiology Laboratoryand Facilities). Questionnaires on QOL were also administered to

all subjects outside the Hospital.

Measurements at pre- and post-trainingAll children consumed their usual breakfast (cereals, milk and

fruit juice) three hours before the test protocols described below.

All performed a graded exercise test on a treadmill (Technogym

Run Race 1400 HC; Technogym, Gambettola, Italy) for the deter-

mination of VO2peak and ventilatory threshold (VT). Each child

performed at least one familiarization session prior to the actual

treadmill test. Treadmillspeedbegan at 1.0 km h1 (or 1.5 km h1

for the oldest participants) with a grade of 5.0%. Thereafter both

treadmill speed and inclination were increased (by 0.1 km h1

and 0.5 %, respectively) every 15 s. The tests were terminated

upon volitional fatigue of the children and/or when they showed

loss of ability to maintain the required workload. During the

tests, the children could not see their parents, but were given

verbal encouragement by the investigators. Gas-exchange data

were measured breath-by-breath using open circuit spirometry

and specific pediatric face masks (Vmax 29C, Sensormedics, Yorba

Linda, CA, USA). VO2peak and peak heart rate (HRpeak) were re-

corded as the highest value obtained for any continuous 20-sec-

ond period [38]. The VO2 (ml kg 1 min1) at the VT was deter-

mined using the criteria of an increase in both the ventilatory

equivalent of oxygen (VE VO21) and end-tidal pressure of oxy-

gen (PetO2) with no increase in the ventilatory equivalent of car-

bon dioxide (VE VCO21) [38].

All treadmill tests were performed under similar environmental

conditions (20 to 248C, 45 to 55% relative humidity) and at the

same time of the day (10:00a.m. 1:00p.m.). Heart rate (HR)

was continuously monitored during the tests from a twelve lead

ECG (Quest Exercise Stress System, Burdick Inc., Milton, WI,

USA).

In order to minimize the influence of a possible learning effect

on strength tests (due to improvement of technique and coordi-

nation and/or diminishment of muscle inhibition) and thus to

stabilize the initial test results, before the start of the study, all

patients underwent a familiarization period. The familiarization

period consisted of three 60-min sessions/week for a total of two

weeks.Each session was preceded by a warm-up and endedwith

a cool-down of the same activities and duration used during the

training period of the study. The body of each familiarization

session consisted of two three sets of one three repetitions

of the exercises (seated bench press, seated lateral row, seated

leg press) used to evaluate muscular strength. Children were also

familiarized (i.e., two three repetitions) with the tests used to

evaluate functional mobility (Time Up and Down Stairs test and

3- and 10-m Time Up and Go tests).

Test-retest assessments of strength and functional mobility eval-

uations were preceded by a warm-up period including aerobic

and stretching exercises (~ 10 min). We found no significant dif-

ference (p > 0.05) between the mean results of test-retest assess-

ments for all the strength and functional mobility evaluations

440


Clinical Sciences


3/8

that are described below. Thus, any potential learning effect on

the results of the variables determined should be minimal.

Dynamic upper and lower-body muscle strength endurance were

measured using a seated bench, seated lateral row, and seated

leg-press machine (Strive Inc.), respectively. The six repetition

maximum (6 RM) value was measured in kg and is described as

the maximum strength capacity to perform six repetitions until

momentary muscular exhaustion. The testing protocol consisted

of three warm-up sets at 50, 70 and 90% of the perceived 6 RMseparated by one-minute rest periods [21].A two-minute restpe-

riod followed the last warm-up set after which a 6 RM attempt

was made at 100105% of perceived 6 RM depending upon the

effort needed to perform the last warm-up set at 90% of the per-

ceived 6 RM. If the first 6 RM attempt was successful, the resis-

tance wasincreased2.5 5% andafter twominutes of rest, anoth-

er 6 RM attempt made. If the second 6 RM attempt was success-

ful, a second testing sessionwas scheduledafter 24 hours of rest.

If the first 6 RM attempt was not successful, the resistance was

decreased 2.55% and after 2 minutes of rest, another 6 RM at-

tempt made. If the second 6 RM attempt was successful, the

weight usedwas consideredthe 6 RM. Ifthe second6 RMattempt

was not successful, another testing session was scheduled after

24 hours of rest. Each subject was instructed to perform each ex-

ercise to momentary muscular exhaustion. Any repetitions not

performed with a full range of motionwere not counted.

To measure childrens functional mobility, we used the Time Up

and Go (TUG) tests of 3- and 10 m and the Timed Up and Down

Stairs (TUDS) test [15]. Both types of tests have been shown reli-

able and valid in healthy children and also in children with vari-

ous diseases or disabilities [15, 27]. The TUG tests of 3- and 10 m

are measures of the time needed to stand up from a seated posi-

tion in a chair, walk 3 and 10 m respectively, turn around, return

to the chair, and sit down. For the TUDS test, the time it took to

ascend and descend 12 stairs was measured [15]. All the children

used a hand railing in the tests. The use of a railing while ascend-

ing and descending the stairs was allowed to diminish the risk of

falling. Performance time in all the tests was measured by the

same investigator with the same stopwatch to the nearest 0.1 s.

A goniometer was used to measure ankle dorsiflexion passive

and active range of motion (ROM). Ankle dorsiflexion passive

(passive DF-ROM) and active (active DF-ROM) range of motion

was measured with the children sitting with the knee flexed to

908 and the foot in neutral alignment [33].

The QOL of the childrenwas assessed with the Child Report Form

of the Childs Health and Illness Profile-Child Edition (CHIP-CE/

CRF) and Adolescent Edition (CHP-PE/AE), which is a self-report

health status instrument for children [34,35] and of their pa-

rents rating of their childrens QOL [36]. The CHIP-CE/CRF in-

cludes five domains: Satisfaction (with self and health), Comfort

(concerning emotional and physical symptoms and limitations),

Resilience (positive activities that promote health), Risk Avoid-

ance (risky behaviors that influence future health), and Achieve-

ment (social expectations in school and withpeers). In our study,

after obtaining permission from the authors and the correspond-

ing institution (see Acknowledgements section), we used the

Spanish version of the CHIP-CE and CHIP-AE, which has been

shown to be valid in Spanish children [34].

Training intervention exercise programAll children in the BMT group followed an 8-week training pro-

gram, consisting of three weekly sessions with a duration rang-

ing from 90 min (in the first few weeks of the program) to

120 min (by the end of the program). The program was individu-

ally supervised (i.e., one instructor for every two children). A pe-

diatrician was also present at each of the training sessions. Each

session started and ended with a low intensity 15-min warm-up

and cool-down period, respectively, consisting of cycle ergom-

eter pedalling at very light workloads and stretching exercises

involving all major muscle groups. The core portion of the train-

ing session was divided into strength and aerobic exercises.

Strength training included 11 exercises engaging the majormuscle groups (bench press, shoulder press, leg extension, leg

press, leg curl, abdominal crunch, low back extension, arm curl,

elbow extension, seated row, and lateral pull-down). For each

exercise, the children performed one set of eight to 15 repeti-

tions (total of~ 20 s duration). Rest periods of one two min sep-

arated the exercises. Stretching exercises of the muscles involved

in the previous exercise were performed during the rest periods

between exercises [1]. The load was gradually increased as the

strength of each child improved.

Aerobic exercises consisted of pedalling on a cycle ergometer,

running, walking and aerobic games involving large muscle

groups, i.e., jumping exercises, ball games, group games, etc.

Aerobic and group games were necessary to maintain and im-

prove the childrens adherence to the training program, i.e., by

making every session different, the childrens compliance and

retention of subjects was maintained. The duration and intensity

of the aerobic training was gradually increased over the training

period so that the subjects started with at least 10 min of aerobic

exercises at 50% age-predicted maximum heart rate (HRmax, es-

timated as 220 age) and progressed to at least 30 min of con-

tinuous exercise at 70% HRmax by the end of the program. All

children wore a portable HR monitor during the sessions to

monitor their exercise intensity.

Each child was evaluated by his/her oncologist every two weeks

during the training period. These examinations included a thor-

ough physical evaluation, complete hematological and biochem-

ical blood analysis. All the children and their parents were in-

structed to follow the childrens usual nutritional habits

throughout both the familiarization and training period. None

of the children were taking any nutritional supplement during

the entire duration of the project.

Data analysisStatistical analyses were performed with the Statistical Package

for Social Sciences (SPSS) 11.5 software (SPSS Inc., Chicago, IL,

USA). Mean values of all the variables at baseline were compared

between both groups using independent t-tests (for parametric

data) or Mann-Whitney U tests (for categorical data, i.e., QOL).

In order to evaluate the combined effect of group and time in

body mass, cardiorespiratory indices (VO2peak, HRpeak and VT),

TUDS test and active and passive dorsiflexion, independent t-

tests were used to compare the change in mean values over time

(post-intervention minus pre-intervention) in training (BMT)

and control groups. For the same purpose, the mean change over

time (post-intervention minus pre-intervention) in BMT vs. con-

trol groups in QOL was compared using the Mann-Whitney U

test. We have used the same statistical approach, which allows

to minimize the risks of multiplicity of statistical analyses (and

thus of having a p value < 0.05 due to chance alone) in previous

training research on cancer survivors [17].

For those variables that were only measured in the BMT group

(i.e., results of strength and TUG tests), we compared pre- vs.

post-training values using paired t-tests. The level of signifi-

441


Clinical Sciences


4/8

cance was set at 0.05 for all statistical analyses and results are

expressed as mean SD.

Results!

Body mass did not differ between groups at pre- (BMT:

33.5 13.5 kg; controls: 32.5 13.2 kg) or post-training (BMT:

34.2 15.1 kg; controls: 35.8 11.4 kg). No significant changes

were observed over time in body mass within each group.

Adherence to training was above 70% in seven children, who had

no health problem over the training period. Their hematological

and biochemical blood parameters remained within normal lim-

its and physical examinations revealed no abnormality. One

child had some major health problems (pulmonary infection),

which decreased her adherence to 50%.

Performance in the TUDS test at baseline was significantly lower

in BMT children compared to controls (p < 0.05), although no dif-

ference was found for active or passive DF-ROM (l" Fig.1). A sig-

nificant combined effect of group and time was observed for the

TUDS test (p < 0.05) whereas passive and active DF-ROM did not

significantly improve over the study period in the training (BMT)

group compared with healthy controls (p > 0.05) (l" Fig.1).

Performance in the TUG-3m, TUG-10m and strength tests signif-

icantly improved after training in the BMT group (p < 0.05)

(l" Figs. 2 and 3).

Mean values of VO2peak and VT at baseline were significantly

lower in BMT children compared with controls (l" Fig. 4). A sig-

nificant combined effect of group and time (p < 0.05) was ob-

served for VO2peak (mL/kg/min) whereas no change was ob-

served in VT over the study period in the training (BMT) group

compared with healthy controls (p > 0.05). No difference existed

in HRpeak at baseline (p > 0.05) and no combined effect of group

and time (p > 0.05) was found for this variable (l" Fig. 4). Thus,

the aforementioned improvement in VO2peak was solelyattribut-

able to the training program and not to possible differences in

the effort level provided by the children before and after train-

ing.

A significant combined effect of group and time (p < 0.05) was

observed for childrens self-report of comfort and resilience

DF

-ROM

()

Passive

Active

Pre

Performanc

ein

TUDStest

(s)

Training(BMT) group Control group

*11

10

9

8

7

6

5

4

3

2

1

0Post

40

30

20

10

0Pre Post Pre Post

Fig.1 Mean SD values of performance in functional mobility (TUDS

test) and active and passive dorsiflexion range of motion. Abbreviations:

Pre (before intervention period), Post (after intervention period), DF-ROM

(dorsiflexion range of motion), TUDS (Time Up and Down). Overall

changein means (i.e., the change [post minus premeans] for thetraining

[BMT] group minus the change [post minus pre means] for the controlgroup) averaged 2.1 (95 %CI: 5.9; 6.7) for passive DF-ROM, 3.8

(95%CI: 6.2; 4.5) for active DF-ROM and 1.3 (95 %CI: 2.0; 0.1) for

the TUDS test. Symbols: p < 0.05 for the comparison between groups at

baseline (Pre); * p < 0.05 for the combined effect of group and time.

Performan

ceinTUGtests(s)

3 m*

10m*15

10

5

0

Pre Post Pre Post

Fig. 2 Mean SD values of performance during functional mobility tests

(TUG) in patients (BMT children). Abbreviations: Pre (before intervention

period), Post (after intervention period), TUG (Time Up and Go). Symbol:

* p < 0.05 for the comparison of pre- vs. post-training.

Performancein6RM

tests(kg)

*Bench press

*

Seated row*

Leg press100

90

80

70

60

50

40

30

20

10

0

Pre Post Pre Post Pre Post

Fig. 3 Mean SD values of performance during strength endurance

(6 RM) tests in patients (BMTchildren). Abbreviations: Pre (before inter-

vention period), Post (after intervention period). Symbol: * p < 0.05 for the

comparison of pre- vs. post-training.

442


Clinical Sciences


5/8

(l" Table 1) and for parents score report of their childrens satis-

faction and achievement (l" Table 2).

Discussion!

Our study shows for the first time that a relatively short-length

duration (8 weeks) intrahospital structured, supervised training

program combining cardiorespiratory and resistance exercisespositively affects changes in VO2peak, muscle strength, functional

mobility and QOL in young children (< 16 yrs) survivors of leuke-

mia who have recently undergone BMT for leukemia treatment.

Many of these patients also receive aggressive immunosuppres-

sive therapy after BMT (i.e., daily corticosteroids) for the preven-

tion/treatment of graft-versus-host disease, a multiorgan in-

flammation that occurs after allogeneic BMT [39]. Our prelimi-

nary findings suggest that this subpopulation can safely undergo

this type of supervised training in other hospitals of the world.

Our findings are of special relevance given i) the frequent several

transplant-related toxicities (e.g., altered cardiorespiratory func-

tion or graft-versus-host disease), which compromise full reha-

bilitation and result in early fatigue during physical activities of

daily living [3,41], and ii) the deleterious effects of immunosup-

pressive therapy associated with BMT (especially, aggressive

corticosteroid therapy) on the ultrastructure and function of

skeletal muscles, including declined myofibrillar mass, altered

aerobic metabolism (due to decreased mitochondrial volume

and/or mitochondrial myopathy), or reduced capillarization

[18]. One potential limitation of our study comes from the fact

that some degree of spontaneous improvement in childrens fit-

ness levels is to be expected after a certain period of time (e.g., a

few months) has elapsed following BMT. This would artificially

inflate the improvements we observed in their exercise capacity

after the training program. The aforementioned limitation was

minimized by the fact that the duration of post-transplant time

did not surpass 12 months in our patients. Such a period of time

Table 1 Mean SD of childrens report of their health status: Child Report Form of the Child Health and Illness Profile-Child Edition (CHIP-CE/CRF) [35]

Domain BMT Group Control Group Overall change

in means

95%CI for overall

change in meansPre Post Pre Post

Satisfaction 3.5 0.5 3.6 0.5 4.3 0.4 4.3 0.4 0.1 0.2; 0.5

Comfort 3.8 0.5 4.4 0.6 4.6 0.2 4.5 0.2 0.7* 0.1; 1.4

Resilience 3.0 0.6 3.4 0.4 4.1 0.3 3.9 0.3 0.6* 0.1;1.3

Risk avoidance 4.1 0.3 4.2 0.2 4.2 0.4 4.0 0.6 0.3 0.1; 0.7

Achievement 2.7 1.0 2.5 0.7 3.6 0.4 3.6 0.4 0.2 0.9; 0.5

Abbreviations: Pre (before intervention period), Post(after theintervention period). Overallchange in meansis the change (post minus pre means) for thetraining(BMT) group

minus the change (post minus pre means) for the control group. Symbol: * p < 0.05 for the combined effect of group and time

Table 2 Mean SD of the childrens parents evaluation of their childs quality of life: Parent Report Form of the Child Health and Illness Profile-Child Edition

(CHIP-CE/CRF) [36]

Domain BMT Group Control Group Overall change

in means

95%CI for overall

change in meansPre Post Pre Post

Satisfaction 3.4 1.0 3.7 1.0 4.0 0.3 4.0 0.3 0.3* 0.0;0.6

Comfort 3.5 0.7 3.7 0.8 4.1 0.4 4.1 0.4 0.2 0.2; 0.5

Resilience 3.6 0.6 3.7 0.6 3.8 0.2 3.8 0.2 0.0 0.1; 0.3

Risk avoidance 4.1 0.4 4.3 0.2 3.9 0.6 3.9 0.5 0.2 0.1; 0.4

Achievement 3.3 0.9 3.7 0.9 3.7 0.2 3.7 0.2 0.4* 0.1; 0.8

Abbreviations: Pre (before intervention period), Post(after theintervention period). Overallchange in meansis the change (post minus pre means) for thetraining(BMT) group

minus the change (post minus pre means) for the control group. Symbol: * p < 0.05 for the combined effect of group and time

VT

Training(BMT) group Controlgroup

Post

200

150

100

50

0

H

R

(beats/min)

pea

k

mLO

/kg/min

2

50

40

30

20

10

0

Pre

VO *2peak

Pre Post Pre Post

Fig.4 Mean SD peak values of endurance indices obtained in the

treadmill exercise tests. Abbreviations: Pre (before intervention period),

Post (after intervention period), VO2peak (peak oxygen uptake), HRpeak(peak heart rate),VT (ventilatory threshold). Overall change in means

(i.e., the change [post minus pre means] for the training [BMT] group mi-

nus the change [post minus pre means] for the control group) averaged

6.3 (95%CI: 2.2; 11.0) for VO2peak, 3.5 ( 2.9; 8.5) for VT and 1.2 (0.1; 2.3)

for HRpeak

. Symbols: p < 0.05 for the comparison between groups at

baseline (Pre); * p < 0.05 for the combined effect of group and time.

443


Clinical Sciences


6/8

is not long enough to allow for a total disappearance of post-

transplant complications. For instance, lung function (i.e., lung

volume and gas diffusion capacity) is still impaired, at least

partly, one year after transplantation [24] and a total of 2 years

might be necessary before lung complications totally disappear

[14]. Cardiac abnormalities can persist for as long as ~ 3 years

post-BMT [10]. In fact, the VO2peak of BMT recipients is still de-

creased (i.e., 69% of predicted) at 6 years after transplantation

[19].The pre-training values of VO2peak and VT of our patients

(~ 26mL O2/kg/min and ~ 18 mL O2/kg/min, respectively) were

clearly below those of the control group and also below the ex-

pected values for healthy children of the same age range, i.e.,

VO2peak ~ 40 45 mL/kg/min [2] and VT > 25 mL/kg/min [4,16,

25,26] and similar to those previously reported in the same type

of diseased population [10,19,20,22]. After completion of the

training program, patients VO2peak values significantly im-

proved, i.e., mean change of + 5.2 mL/kg/min. Such a finding is

of clinical significance as VO2peak is an excellent indicator of

health status and an independent predictor of mortality, i.e., an

increase of only 3.5 mL/kg/min is associated with a 12% increase

in survival rate in both healthy and diseased adults [31]. Of espe-

cial relevance was the fact that the aforementioned improve-

ment in VO2peak was obtained despite a relatively low adherence

to training (~ 70%), i.e., considerably lower than that (> 85%) re-

ported by our group in children who had not received BMT and

were training while undergoing maintenance treatment against

leukemia (with a final improvement in their VO2peak of~ +6mL/

kg/min) [38]. On the other hand, our findings are in agreement

with previous studies on adult patients who had undergone

BMT and gained significant improvements in their fitness level

after aerobic [7] or strength exercise training [9].

The VT values in our patients (~ 18 mL kg1 mL1) were consid-

erably lower than those previously reported in survivors of leu-

kemia < 13 years of age, i.e., ~ 24 mL/kg/mL [36]. The VT is a

health indicator in diseased populations [30]. Exerciseinduced

improvements in this variable result in attenuation of breath-

lessness, improved exercise capacity at submaximal levels, and

contribute to the well-being of patients during their daily activ-

ities [30]. Although we have previously observed improvements

in the VT values of children with leukemia (not receiving BMT),

after 16 weeks of supervised exercise training [38], in the

present study, VT did not significantly improve after an 8-week

training program. One potential explanation for the lack of im-

provement in patients VT might lie on the fact that an important

amount of their endurance training was performed at intensities

higher than the VT, at least by the end of the program (i.e., in-

tensity > 70% HRmax whereas their VT corresponded to ~ 60%

HRmax). Longer (and possibly less intense) training programs

and/or higher adherence to training would seem necessary to

elicit significant gains in this variable.

Dynamic upper and lower-body muscle strength improved with

training. The strength levels of our subjects are difficult to com-

pare with those of other diseased children as muscle strength is

not commonly measured in diseased children, included children

who have undergone BMT, despite the importance of this varia-

ble. The pre-training strength values of our patients (aged 8

16 yrs) were higher than those reported by us using the same

equipment and tests in children undergoing maintenance che-

motherapy against leukemia [38]. Such a difference might be at-

tributable to the higher age (and thus different maturity status)

of the present subjects. The strength gains obtained in our pa-

tients after completing the 8-week training program (seated

bench press: ~ 8%; seated row: ~ 18%; leg press: ~ 11%) were

overall lower than those we previously reported in younger

(< 7 yrs) children with leukemia with a training intervention of

the same duration (seated bench press: ~ 20%; seated row:

~ 20%; leg press ~ 9 %) [37]. Such a difference may be attributed,

at least partly, to the lower adherence to the training program in

the present subjects (~ 70% vs. > 85% in younger children with

leukemia [37]). We chose to assess dynamic muscle strength en-durance (six repetition maximum, 6 RM) instead of maximal dy-

namic strength (one repetition maximum, 1 RM) in order to ob-

tain results of practical relevance for children, in whom maximal

strength is not a main determinant of their ability to perform

physical activities of daily living, which are mostly submaxi-

mal-strength tasks, e.g., climbing stairs, sitting and rising from

a chair, outdoor activities, etc.

In line with previous research of younger children withleukemia

[37, 38] we also found significant training-induced improve-

ments in the TUDS, TUG-3-m and 10-m tests after the exercise

program intervention, indicating a significant gain in muscle

functional capacity and in tasks of daily living. On the other hand,

passive and active DF-ROM did not significantly improve with

training. This finding is in agreement with previous research on

children with leukemia [38], though Marchese et al. [27] re-

ported improvements in active DF-ROM after a 16-week physical

therapy protocol. As opposed to the very low pre-training values

of VO2peak or muscle strength, the patients in the present study

had sufficient DF-ROM at baseline for sustaining normal activ-

ities of daily living, such as normal gait patterns [42].

We found significant improvements in some of the main items

of the childrens (comfort and resilience) and parents self-re-

ported QOL (satisfaction and achievement) after the training in-

tervention. This result is in apparent disagreement with pre-

vious research on younger children with leukemia showing a

nonsignificant trend towards an improvement in QOL [27,38].

Such lack of significance was attributed to a certain ceiling ef-

fect during the pre-training questionnaire, with the majority of

children and parents minimizing their actual QOL problems be-

fore the training intervention, i.e., reporting having no problems

with the items on the questionnaire (health status, satisfaction,

etc.). The older age and maturity status of the present subjects

might contribute to a more objective evaluation of their QOL be-

fore engaging the training program and thus to prevent the

aforementioned ceiling effect that would minimize actual im-

provements in QOL.

Our findings do also emphasise the need for performing individ-

ualized, supervised training for children with leukemia, prefera-

bly in a hospital setting. Marchese et al. [27] studied the effect of

a 16-wk physical therapy intervention program in children with

leukemia combined with home-based exercises (aerobic train-

ing, stretching exercises). No significant improvements in indi-

rectly estimated aerobic capacity (i.e., 9-min run-walk test) and

functional mobility (i.e., TUDS test) were observed after this in-

tervention. In contrast, our supervised intrahospital training

program including both aerobic and strength training did induce

significant improvements in directly measured maximal aerobic

capacity (VO2peak), muscle strength endurance and functional

mobility (TUDS, TUG-3 m, TUG-10 m), suggesting the need for

performing individually supervised training programs as the

one used here (i.e., one instructor for every two children) instead

of home-based training. The need for an individually supervised

program to bring about maximal fitness gains is supported by

444


Clinical Sciences


7/8

previous research showing that an individually supervised

strength training program results in significantly greater

strength gains than a program involving instruction, but having

the subjects perform the training on their own [28].

In summary, although more research using larger population

groups is necessary to corroborate our preliminary findings,

young children (816 years) who have recently ( 12 months)

undergone bone marrow transplantation for the treatment of

leukemia can safely undergo an intrahospital structured, super-vised conditioning program. This program should include both

aerobic and resistance exercise training to induce significant

health benefits (improved aerobic fitness, muscle strength, func-

tional mobility and important aspects of QOL) in only 8 weeks.

Acknowledgements!

This study was supported by research grants from Fondo de In-

vestigaciones Sanitarias (FIS) (ref. # PI061183) and European

University of Madrid (ref. # UEM/2005/1). We also acknowledge

Agncia dAvaluaci de Tecnologia i Recerca Mdiques (AATRM)

(Barcelona, Spain) for permission to use the Spanish version of

the Child Report Form of the Child Health and Illness Profile-

Child Edition (CHIP-CE/CRF; CHIP-AE).

References1 American Academy of Pediatrics. Strength training, weight and power

lifting and bodybuilding by children and adolescents. Pediatrics1990; 86: 801803

2 Bar-Or O, Rowland TW (eds). Pediatric Exercise Medicine: From Phys-iologic Principles to Health Care Application. Champaign IL: HumanKinetics, 2004: 5 7

3 Carlson K, Smedmyr B, Bcklund L, Simonsson B. Subclinical disturban-ces in cardiac function at rest and in gas exchange during exercise arecommon findings after autologous bone marrow transplantation.Bone Marrow Transplant 1994; 14: 949954

4 Cooper DM, Weiler-Ravell D, Whipp BJ, Wasserman K. Aerobic parame-ters of exercise as a function of body size during growth in children. JAppl Physiol 1984; 56: 628634

5 Cunningham BA, Morris G, Cheney CL, Buergel N, Aker SN, Lenssen P.Ef-fects of resistive exercise on skeletal muscle in marrow transplant re-cipients receiving total parenteral nutrition. J Parenter Enter Nutr1986; 10: 558 563

6 De Caro E, Fioredda F, Calevo MG, Smeraldi A, Saitta M, Hanau G, FaraciM, Grisolia F, Dini G, Pongiglione G, Haupt R. Exercise capacity in ap-parently healthy survivors of cancer. Arch Dis Child 2006; 91: 4751

7 Dimeo F, Bertz H, Finke J, Fetscher S, Mertelsmann R, Keul J. An aerobicexercise program for patients with haematological malignancies afterbone marrow transplantation. Bone Marrow Transplant 1996; 18:1157 1160

8 Dimeo F, Fetscher S, Lange W, Mertelsmann R, Keul J. Effects of aerobicexercise on the physical performance and incidence of treatment-re-

lated complications after high dose chemotherapy. Blood 1997; 90:339033949 Dimeo F, Tilmann MHM, Bertz H, Kanz L, Mertelsmann R, Keul J. Aerobic

exercise in the rehabilitation of cancer patients after high dose che-motherapy and autologous peripheral stem cell transplantation. Can-cer 1997; 79: 1717 1722

10 Earnes GM, Crosson J, Steinberger J, Steinbuch M, Krabill K, Bass J, Ram-say NK, Neglia JP. Cardiovascular function in children following bonemarrow transplant: a cross-sectional study. Bone Marrow Transplant1997; 19: 61 66

11 Faigenbaum AD, Westcott WL,Micheli LJ,Outerbridge AR,Long CJ,La Ro-sa-Loud RL. The effects of strength training and detraining on children.J Strength Cond Res 1996; 10: 109 114

12 Felder-Puig R, Di Gallo A, Waldenmair M, Norden P, Winter A, Gadner H,Topf R. Health-related qualityof lifeof pediatric patientsreceivingallo-geneic stem cell or bone marrow transplantation: results of a longitu-

dinal, multi-centerstudy.Bone Marrow Transplant 2006;38: 119 126

13 Fournier M, Ricci J, Taylor AW, Ferguson RJ, Montpetit RR, Chaitman BR.Skeletal muscle adaptation in adolescent boys: sprint and endurancetraining and detraining. Med Sci Sports Exerc 1982; 14: 453456

14 Gandola L, Siena S, Bregni M, Sverzellati E, Piotti P, Stucchi C, Gianni AM,Lombardi F et al. Prospective evaluation of pulmonary function in can-cer patients treated with total body irradiation, high-dose melphalanand autologous hematopoietic tem cell transplantation. Int J RadiatOncol Biol Phys 1990; 19: 743749

15 GochaMarcheseVG, Chiarello LA, Lange BJ.Strength and functional mo-bility in childrenwith acute lymphoblastic leukemia. Med Pediatr On-

col 2003; 40: 230 23216 Hebestreit H, Staschen B, Hebestreit H. Ventilatory threshold: a usefulmethod to determine aerobic fitness in children. Med Sci Sports Exerc2000; 32: 1964 1969

17 Herrero F, San Juan AF, Fleck SJ, Balmer J, Perez M, Caete S, Earnest CP,Foster C, Lucia A. Combined aerobic and resistance training in breastcancer survivors: a randomized, controlled pilot trial. Int J SportsMed 2006; 27: 573580

18 Hickson RC, Marone RJ. Exercise and inhibition of glucocorticoid-in-duced muscle atropy. Exerc Sport Sci Rev 1993; 21: 135167

19 Hogarty AN, Leahey A, Zhao H, Hogarty MD, Bunin N, Cnaan A, ParidonSM. Longitudinal evaluation of cardiopulmonary performance duringexercise after bone marrow transplantation in children. J Pediatrics2000; 136: 311 317

20 Jenney ME, Faragher EB, Jones PH, Woodcock A.Lungfunctionand exer-cise capacity in survivors of childhood leukaemia. Med Pediatr Oncol

1995; 24: 222 23021 Kraemer W, Fry A. Strength testing development and evaluation of

methodology. In: Mauch PJ, Foster C (eds). Physiological Assessmentof Human Fitness. Champaign IL: Human Kinetics, 1995: 115 138

22 Larsen RL, Barber G, Heise CT, August CS.Exercise assessment of cardiacfunction in children and young adults before and after bone marrowtransplantation. Pediatrics 1992; 89: 722729

23 Lucia A, Ramirez M, San Juan AF, Fleck SJ, Garca-Castro J, Madero L. In-trahospital supervised exercise training: a complementary tool in thetherapeutic armamentarium against childhood leukaemia. Leukemia2005; 19: 13341337

24 Lund MB, Kongerud J, Brinch L, Evensen SA, Boe J. Decreased lung func-tion in one year survivors of allogeneic bone marrow transplantationconditioned with high-dose busulphan and cyclophosphamide. EurRespir J 1995; 8: 12691274

25 Mahon AD, Gay JA, Stolen KQ. Differentiated ratings of perceived exer-

tion at ventilatory threshold in children and adults. Eur J Appl PhysiolOccup Physiol 1998; 78: 115 120

26 Mahon AD, Marsh ML. Reliability of the rating of perceived exertion atventilatory threshold in children. Int J Sports Med 1992; 13: 567571

27 Marchese VG, Chiarello LA, Lange BJ. Effects of physical therapy inter-vention for childrenwith acute lymphoblastic leukemia.Pediatr BloodCancer 2004; 42: 127133

28 Mazzetti SA, Kraemer WJ, Volek JS, Duncan ND, Ratamess NA, Gomez AL,Newton RU, Hakkinen K, Fleck SJ. The influence of direct supervision ofresistance training on strength performance. Med Sci Sports Exerc2000; 32: 1175 1184

29 Mello M, Tanaka C, Dulley FL. Effects of an exercise program on muscleperformance in patients undergoing allogeneic bone marrow trans-plantation. Bone Marrow Transplant 2003; 32: 723728

30 Meyer T, Lucia A, Earnest CP, Kindermann W. A conceptual frameworkfor performance diagnosis and training prescription from submaximal

parameters theory and application.Int J SportsMed 2005; (Suppl1):S38S48

31 Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercisecapacity and mortality among men referred for exercise testing. NEngl J Med 2002; 4: 793 801

32 National Strength and Conditioning Association. Youth resistance train-ing: position statement paper and literature review. J Strength CondRes 1996; 18: 6276

33 Norkin CC, White DJ (eds). Measurement of Joint Motion: A Guide toGoniometry. 3rd edn. Philadelphia, PA: FA Davis Company, 2003:256259

34 Rajmil L, Serra-Sutton V, Alonso J, Starfield B, Riley A, Vquez JR. TheSpanish version of the child health and illness profile-adolescent edi-tion (CHIP-AE). Quality of Life Res 2003; 12: 303313

35 Riley AW, Forrest CB,Rebok GW,Starfield B, Green BF, RobertsonJA, Friel-lo P. The child report form of CHIP-child edition: reliability and valid-

ity. Med Care 2004; 42: 221231

445


Clinical Sciences


8/8

36 Riley AW, Forrest CB, Starfield B, Rebok GW, Robertson JA, Green BF. Theparent report form of the CHIP-child edition: reliability and validity.Med Care 2004; 42: 210220

37 San Juan AF, Fleck SJ, Chamorro-Via C, Mat-Muoz JL, Moral S, Garca-Castro J, Ramirez M, Madero L, Lucia A. Early-phase adaptations to in-tra-hospital training in strength and functional mobility of childrenwith leukemia. J Strength Cond Res 2007; 21: 173177

38 San Juan AF, Fleck SJ, Chamorro-Via C, Mat-Muoz JL, Moral S, PrezM, Ramirez M, Madero L, Lucia A. Effects of an intra-hospital exerciseprogram intervention for children with leukemia. Med Sci Sports Ex-

erc 2007; 39: 13 21

39 Stevens AM, Sullivan KM, Nelson JL. Polymyositis as a manifestation ofchronic graft-versus-host disease. Rheumatology 2003; 42: 34 39

40 Tsolaris CK, Vagenas GK, Dessypris AG. Strength adaptations and hor-monal responses to resistance training and detraining in preadoles-cent males. J Strength Cond Res 2006; 18: 625629

41 van Brussel M, Takken T, Lucia A, van der Net J, Helders PJ.Is physical fit-ness decreased in survivors of childhood leukemia? A systematic re-view. Leukemia 2005; 19: 1317

42 Wright MJ, Hanna SE, Haltona JM, Barr RD. Maintenance of ankle rangeof motion in children treated for acute lymphoblastic leukaemia. Ped

Phys Ther 2003; 15: 146152

446

San Juan AF et al Pediatric Bone Marrow Transplantation and Exercise Int J Sports Med 2008; 29: 439 446

Clinical Sciences

Benefits of Intrahospital Exercise Training After

Documents

Transcript of Benefits of Intrahospital Exercise Training After