IJC

International Journal of Cancer

Quality of life during active treatment for pediatric acute

lymphoblastic leukemia
Lillian Sung1, Rochelle Yanofsky2, Robert J. Klaassen3, David Dix4, Sheila Pritchard4, Naomi Winick5, Sarah Alexander1
and Anne Klassen6
1
Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children and Department of Paediatrics, University of Toronto,
Toronto, ON, Canada
2
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada
3
Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada
4
Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
5
Department of Pediatric Hematology/Oncology, UT Southwestern Medical Center, Dallas, TX
6
Department of Pediatrics, McMaster University, Hamilton, ON, Canada

The objectives of the study were to describe quality of life (QoL), identify predictors of worse QoL and examine QoL during
different phases of active therapy for acute lymphoblastic leukemia (ALL). A multiinstitutional cross-sectional study was
performed in children with ALL. We included children at least 2 months from diagnosis who were receiving treatment in first
remission. Parents described QoL using the PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Acute Cancer Module. The
206 children on treatment for ALL had overall [median 62.5, 95% confidence interval (CI) 34.8–94.4], physical (median 62.5,
95% CI 18.8–100.0) and psychosocial (median 65.4, 95% CI 38.3–94.2) summary scores that were one to two standard
deviations lower than population norms. In high-risk ALL, girls and older children had worse QoL. In standard-risk ALL, those
with lower household incomes and unmarried parents had worse QoL. QoL scores were generally constant across phases of
ALL therapy. Children on therapy for ALL have lower QoL compared to healthy children. Age and gender predicted QoL in high-
risk ALL, whereas socioeconomics predicted QoL in standard-risk ALL. Future efforts should focus on longitudinal studies that
describe QoL over time within individual patients.

Acute lymphoblastic leukemia (ALL) is the most common
cancer in children. Outcomes for children with ALL have
continued to improve over time, and currently, almost 80%
of children are cured of their disease with primarily outpa-
tient chemotherapy.1 Because cure rates have increased, more
emphasis has been placed on reducing toxicities of therapy,
improving quality of life (QoL) during treatment and mini-
mizing long-term effects of therapy. Contemporary chemo-
therapy regimens for childhood leukemia are lengthy with
attention has been directed at understanding QoL during
active therapy.
To date, published QoL research in pediatric cancer has
mainly focused on diverse patient groups, which is appropri-
ate for early exploratory work in describing QoL and validat-
ing instruments. However, as our knowledge of QoL in pedi-
atric cancer progresses, it is important to begin to focus on
specific subpopulations. Most likely, pediatric cancer patients
with differing diagnoses and treatments have different levels

medications administered over 2.5–3.5 years, and thus, more
Key words: acute lymphoblastic leukemia, quality of life, pediatric,
predictors
Abbreviations: ALL: acute lymphoblastic leukemia; CI: confidence
interval; SCT: stem cell transplantation; QoL: quality of life
Additional Supporting Information may be found in the online
version of this article.
Grant sponsors: Canadian Institutes of Health Research, National
Cancer Institute of Canada
DOI: 10.1002/ijc.25433
History: Received 15 Jan 2010; Accepted 25 Mar 2010; Online 4
May 2010
Correspondence to: Lillian Sung, Division of Haematology/
Oncology, Hospital for Sick Children, 555 University Avenue,
Toronto, Ontario, Canada M5G 1X8, Tel.: 416-813-5287, Fax:
416-813-5327, E-mail: lillian.sung@sickkids.ca
Cancer Therapy
and determinants of QoL.
Two systematic reviews have examined measurement of
QoL for children with ALL.2,3 Most research has focused on
survivorship and much less on the period during active treat-
ment.2 Of those studies that have included children during
active treatment, sample sizes for ALL patients have been
small and, in general, have not been designed to identify
those more likely to have worse QoL on therapy or to com-
pare QoL during different phases of treatment.
Thus, research focused on children with ALL during
active treatment is important and remains an area in which
we lack knowledge about predictors of QoL and changes in
QoL over different phases of therapy. Consequently, our
objectives were to describe QoL in a large cohort of children
with ALL in first remission, identify predictors of reduced
QoL and to describe how QoL changes during different
phases of therapy.

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 1214
Material and Methods
Patients
Our study was a subset of a larger project designed to evaluate
psychosocial health in parents of children receiving chemo-
therapy for cancer.4 Children were eligible for inclusion in this
analysis if they were receiving chemotherapy for ALL, if they
had not relapsed and if they had not received stem cell trans-
plantation (SCT). In addition, children were eligible if they
were initially diagnosed more than 2 months before enrollment
on our study and if their therapy was not considered to be pal-
liative as defined as no reasonable chance for cure by their
healthcare team. Finally, children were only eligible if they
were at least 2 years of age (lower limit for instrument avail-
ability), the parent respondent was the person most responsible
for the day-to-day decision making for that child for the past
year and the parent respondent could read English. Children
were enrolled from five tertiary care Canadian pediatric cancer
centers as follows: BC Children’s Hospital (Vancouver), Can-
cerCare Manitoba (Winnipeg), Children’s Hospital of Eastern
Ontario (Ottawa), The Hospital for Sick Children (Toronto)
and McMaster Children’s Hospital (Hamilton).
Methods
Patients were approached for participation either in the inpa-
tient or outpatient setting in a consecutive fashion. The family
was given a booklet to complete in which questions about
child QoL were asked (see Outcomes section below). The
booklet also asked questions about the child, parent and fam-
ily. The booklet was returned to the team in person or by
mail. Child variables included demographic information and
information on diagnosis and treatment. Disease risk status
(high or standard) and information on protocol treatment
were abstracted from hospital records by each institution’s
clinical research associate. High and very high risks were com-
bined for the purpose of this analysis. In the evaluation of
QoL by different phases of therapy, four of the five institutions
used protocols developed by the Children’s Oncology Group
Cancer Therapy
or one of the predecessor groups, the Pediatric Oncology
Group or the Children’s Cancer Group. Therefore, analyses by
phase of therapy were restricted to these four institutions.
Parent variables included demographics, whether the pri-
mary caregiver received an undergraduate degree and
employment and marital statuses. Family variables included
household income and savings. Household income was
reported both as those with a household income
$60,000
annually (approximately median value in this sample) and
the adjusted family income. The adjusted family income is a
measure of income that adjusts for family size and composi-
tion. It accounts for the benefits of multiple wage earners in
the family as well as the economy of multiple individuals liv-
ing in a single household compared to per capita income.5
Institutional research ethics approval was obtained from
each of the participating centers, and written informed con-
sent was obtained from all participants.
Quality of life in acute lymphoblastic leukemia
Outcomes
The PedsQL is a multidimensional instrument that is reliable
and valid in healthy populations and in children with can-
cer.6–11 This instrument is composed of a 23-item PedsQL
4.0 Generic Core Scale that reflects four dimensions, namely
physical, emotional, social and school functioning. In general,
the summary scores available from the PedsQL 4.0 Generic
Core Scales are overall, physical and psychosocial scores with
the psychosocial scores consisting of emotional, social and
school dimensions. We also used the 27-item PedsQL 3.0
Acute Cancer Module that assesses the following eight
dimensions: pain and hurt, nausea, procedural anxiety, treat-
ment anxiety, worry, cognitive problems, perceived physical
appearance and communication.
Scores were transformed on a scale from 0 (worst health)
to 100 (best health). To derive dimension and summary
scores, more than half the items had to be completed for that
dimension. A 1-month recall period was used.
Statistics
Potential predictors of QoL scores were determined using
univariate linear regression analyses. For multiple regression
modeling, demographic, disease-related and socioeconomic
factors that were associated with QoL at p < 0.1 were entered
into a forward selection model. We presented these associa-
tions as b coefficients with their standard errors as derived
from linear regression. Positive b coefficients meant that the
predictor (or increasing values of the predictor) was associ-
ated with better QoL whereas negative b coefficients sug-
gested that the predictor (or increasing values of the predic-
tor) was associated with worse QoL. We also described the
number of children with impaired QoL as defined as those
with a QoL score at least two standard deviations below the
age-specific population mean; these values were derived using
data from a PedsQL database.12
To compare QoL between children in phases of therapy
preceding and during maintenance, the Student’s t-test was
used. All statistical analyses were performed using the SAS
statistical program (SAS-PC, version 9.2; SAS Institute, Cary,
NC). All tests of significance were two sided, and statistical
significance was defined as p < 0.05.
Results
Subjects were enrolled between November 2004 and February
2007. In the overall study that targeted parents of children
with any type of cancer receiving chemotherapy, a total of
513 parents were asked to participate in our study and 501
agreed. We received completed questionnaires back from 412
parents, giving an overall response rate of 80.3%. For this
analysis, in which we focused on children at least 2 years of
age with ALL in first remission and who had not undergone
SCT, 206 parents of children were enrolled and provided
questionnaires.
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Sung et al. 1215

Table 1. Demographics and summary scores in 206 children with acute lymphoblastic leukemia
Variable Value
Child factors
Median child age in years (range) 5.6 (2.3–18.1)
Median years since diagnosis (IQR) 0.7 (0.4–1.4)
No. male child (%) 119/206 (57.8)
No. with high-risk ALL (%) 50/200 (25.0)
No. received radiation (%) 16/206 (7.8)
Parent factors
Median parent age in years (range) 38.0 (20.2–75.9)
No. male parent (%) 22/204 (10.8)
No. first parenting experience (%) 97/201 (48.3)
No. undergraduate degree (%) 56/206 (27.2)
No. working (%) 95/200 (47.5)
No. married (%) 170/206 (82.5)
Household factors
No. annual household income
$60,000 (%) 93/190 (49.0)
Median adjusted household income in dollars (IQR) 27,500 (17,308–42,500)
No. savings
$10,000 (%) 76/177 (42.9)
Quality of life summary scores
Median overall summary score (95% CI)1 62.5 (34.8–94.4)
Median physical summary score (95% CI)2 62.5 (18.8–100.0)
2
Median psychosocial summary score (95% CI) 65.4 (38.3–94.2)
Median emotional summary score (95% CI)1 65.0 (30.0–100.0)
2
Median social summary score (95% CI) 75.0 (40.0–100.0)
Median school summary score (95% CI)3 55.0 (25.0–100.0)
1
n ¼ 201. 2n ¼ 199. 3n ¼ 136.

Table 1 demonstrates child, parent and household demo-
graphic information. The median child age was 5.6 (range
2.3–18.1) years. When divided by age groups, 79 (34%) were
2–4 years, 63 (30.6%) were 5–7 years, 33 (16.0 %) were 8–12
years and 31 (15.1 %) were 13–18 years of age. In addition,
0.0001). Similarly, because all measures of income were
highly correlated (adjusted income and annual family income
of at least $60,000, Spearman r ¼ 0.83, p < 0.0001 and
adjusted income and saving of at least $10,000, Spearman r
¼ 0.56, p < 0.0001), only adjusted income was included in

Table 1 describes the PedsQL overall, physical and psychoso-
cial summary scores as well as the psychosocial dimension
scores of emotional, social and school QoL. For the 206 chil-
dren, summary scores were available for 199 physical scores.
However, because many children did not attend school, only
135 responses were available for the school dimension. The
number of children with physical, emotional and social QoL
scores at least two standard deviations below the population
mean were 55/199 (27%), 47/201 (23%) and 29/199 (15%),
respectively. This analysis takes into account changes in QoL
as a child grows, because QoL scores were compared against
age group-specific normative values.
In developing multiple regression models, highly corre-
lated variables cannot concurrently be included in the same
model. Therefore, only child age was included if both child
age and parent age met criteria for inclusion into the model
because they were highly correlated (Spearman r ¼ 0.50; p <
Cancer Therapy
the model if multiple measures met criteria for inclusion.
Supporting Information Appendices 1 and 2 demonstrate
the univariate predictors of overall, physical, psychosocial
emotional, social and school QoL scores, whereas Table 2
illustrates the results of multiple regression analyses and con-
sequently which variables were independently associated with
QoL. We found that those with high-risk ALL had worse
QoL with respect to overall, physical, psychosocial, emotional
and social scores. Independent of risk status, we also found
that older children had worse overall, psychosocial and
school functioning, whereas girls had worse overall, physical,
psychosocial and social QoL scores. Lower household income
was associated with worse overall, physical, psychosocial and
social QoL scores. Finally, social functioning declined as time
from diagnosis increased.
The Spearman correlation between child age and risk sta-
tus was 0.39, and thus, both were included in multiple

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 1216 Quality of life in acute lymphoblastic leukemia

Table 2. Multiple linear regression for overall, physical, psychosocial, emotional, social and school
quality of life scores in 206 children with acute lymphoblastic leukemia

Adjusted b coefficient 6
Variable standard error p
Overall summary score
Child age 0.71 6 0.30 0.02
Male child 5.82 6 2.35 0.01
High-risk disease 9.20 6 3.09 0.003
Adjusted household income per $10,000 2.18 6 0.70 0.002
Physical summary score
Male child 6.79 6 3.14 0.03
High-risk disease 16.90 6 3.64 <0.0001
Radiation 13.87 6 5.57 0.01
Adjusted household income per $10,000 1.97 6 0.98 0.047
Psychosocial summary score
Child age 0.72 6 0.30 0.02
Male child 5.04 6 2.28 0.03
High-risk disease 5.91 6 2.99 0.049
Adjusted household income per $10,000 1.59 6 0.72 0.03
Emotional summary score
High-risk disease 6.95 0.03
Married 9.66 6 3.68 0.009
Social summary score
Male child 7.62 6 2.72 0.006
Time since diagnosis 3.93 6 1.78 0.03
High-risk disease 12.77 6 3.14 <0.0001
Adjusted household income per $10,000 3.18 6 0.81 0.0001
School summary score
Child age 1.33 6 0.44 0.003

Table 3. Multiple linear regression for overall, physical,
psychosocial, emotional, social and school quality of life scores in
high-risk acute lymphoblastic leukemia (N ¼ 50)
Adjusted b
Cancer Therapy
regression. However, because they are clinically related, we
also chose to conduct multiple regression stratified by risk
status, which are presented in Tables 3 (high risk) and 4
(standard risk). For high-risk ALL, in general, older children

coefficient 6 and girls had worse QoL across all dimensions. In contrast,
Variable standard error p
for standard-risk ALL, socioeconomic variables such as pa-
Overall summary score
rental marital status and household income were associated
Child age 1.33 6 0.43 0.003 with QoL across dimensions.
Male child 13.13 6 4.63 0.007 The analysis by phase of therapy included 137 children
Psychosocial summary score treated at four of the institutions. Risk status was available
Child age 1.77 6 0.40 <0.0001 on 133 and 38 (28.6%) were classified as high risk. Of the
137 children with ALL at the four institutions, 77 were on
Male child 12.46 6 4.31 0.006
phases of therapy preceding maintenance and 60 were on
Emotional summary score
maintenance treatment. For these children, 52 (38.0%) were
Male child 11.44 6 5.50 0.04 treated according to Children’s Cancer Group protocols
Social summary score (CCG 1961 and 1991), 43 (31.4%) were treated according to
Child age 1.63 6 0.50 0.002 Pediatric Oncology Group protocols (POG 9904, 9905 and
Male child 15.32 6 5.36 0.007 9906) and 42 (30.7%) were treated according to Children’s
Oncology Group protocols (AALL0331, AALL0232 and COG
School summary score
A5971). Table 5 illustrates that overall, physical, psychosocial,
Child age 2.71 6 0.51 <0.0001
emotional, social and school QoL scores were qualitatively

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Sung et al. 1217

Table 4. Multiple linear regression for overall, physical, psychosocial, emotional, social and school
quality of life scores in standard-risk acute lymphoblastic leukemia (N ¼ 150)

Adjusted b
coefficient 6
Variable standard error p
Overall summary score
Adjusted household income per $10,000 2.21 6 0.84 0.01
Physical summary score
Male child 7.78 6 3.56 0.03
Radiation 17.22 6 7.14 0.02
Adjusted household income per $10,000 2.84 6 1.08 0.009
Psychosocial summary score
Married 9.65 6 3.45 0.006
Emotional summary score
Married 8.47 6 4.28 0.049
Social summary score
Male child 6.95 6 3.08 0.03
Adjusted household income per $10,000 3.40 6 0.93 0.0004

Table 5. Comparison of quality of life scores during phases preceding maintenance compared with maintenance phase1,2
Preceding maintenance (N 577) Maintenance (N 5 60) p
Summary scores
Overall summary score 63.3 (33.7–90.5) 60.2 (43.5–95.2) 0.305
Physical summary score 60.9 (18.8–96.9) 62.5 (37.5–100.0) 0.152
Psychosocial summary score 66.7 (38.3–88.5) 58.3 (38.3–93.3) 0.152
Emotional summary score 60.0 (25.0–100.0) 65.0 (30.0–100.0) 0.087
Social summary score 75.0 (40.0–100.0) 70.0 (45.0–100.0) 0.784
School summary score 55.0 (30.0–100.0) 55.0 (20.0–91.7) 0.278
Cancer-specific scores
Pain and hurt 62.5 (25.0–100.0) 62.5 (25.0–100.0) 0.751
Nausea 56.7 (10.0–90.0) 70 (40.0–100.0) 0.0003
Procedural anxiety 33.3 (0.0–100.00) 51.2 (0.0–100.0) 0.004
Treatment anxiety 58.3 (0.0–100.0) 75.0 (8.3–100.0) 0.002

Cancer Therapy
Worry 75.0 (16.7–100.0) 100.0 (8.3–100.0) 0.016
Physical appearance problems 83.3 (25.0–100.0) 91.7 (16.7–100.0) 0.697
Communication problems 75.0 (0.0–100.0) 75.0 (8.3–100.0) 0.858
Cognitive problems 70.0 (35.0–100.0) 65.0 (25.0–100.0) 0.289
1
All scores represent median (95% confidence intervals). 2Only children enrolled from BC Children’s Hospital, CancerCare Manitoba, Children’s
Hospital of Eastern Ontario and The Hospital for Sick Children were included in this analysis.

and statistically similar for those receiving treatment during
phases preceding maintenance and during maintenance ther-
apy. Supporting Information Appendix 3 illustrates the actual
scores by specific phases of therapy; in general, generic sum-
mary and dimension scores were similar across all of these
phases other than during intensive continuation, which is a
phase specific to Pediatric Oncology Group trials. When
examining cancer-specific scores, nausea, procedural anxiety,
treatment anxiety and worry improved on maintenance com-
pared to before maintenance treatment. Pain and hurt were
similar between these two time periods.
Table 6 illustrates that although we did not demonstrate
differences in QoL across phases, we were able to identify
differences between standard- and high-risk protocols when
stratified by phase of therapy. More specifically, general
dimensions such as overall, physical, psychosocial and social
scores were worse for high-risk patients compared to stand-
ard-risk patients; this was true both for patients receiving

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 1218 Quality of life in acute lymphoblastic leukemia

Table 6. Comparison of quality of life in standard- versus high-risk patients by phase of therapy1,2
Standard risk High risk p
Phases preceding maintenance n ¼ 50 n ¼ 25
Summary scores
Overall summary score 67.6 (35.9–92.4) 56.0 (29.6–77.2) 0.003
Physical summary score 68.8 (40.6–100.0) 42.2 (15.6–84.4) <0.0001
Psychosocial summary score 67.5 (47.5–100.0) 62.5 (30.0–77.5) 0.006
Emotional summary score 60.0 (30.0–100.0) 60.0 (25.0–80.0) 0.135
Social summary score 75.0 (55.0–100.0) 62.5 (30.0–90.0) 0.001
School summary score 61.7 (35.0–100.0) 50.0 (27.5–100.0) 0.499
Cancer-specific scores
Pain and hurt 62.5 (25.0–100.0) 50.0 (25.0–87.5) 0.021
Nausea 65.0 (30.0–90.0) 47.5 (5.0–70.0) 0.0003
Procedural anxiety 50.0 (0.0–100.0) 25.0 (0.0–100.0) 0.289
Treatment anxiety 66.7 (0.0–100.0) 50.0 (16.7–100.0) 0.495
Worry 91.7 (41.7–100.0) 50.0 (31.3–100.0) 0.0002
Physical appearance problems 91.7 (33.3–100.0) 70.8 (25.0–100.0) 0.030
Communication problems 83.3 (8.3–100.0) 66.7 (0.0–100.0) 0.351
Cognitive problems 75.0 (50.0–100.0) 66.9 (16.7–90.0) 0.039
Maintenance n ¼ 45 n ¼ 13
Summary scores
Overall summary score 64.3 (46.7–95.7) 53.8 (41.3–80.4) 0.058
Physical summary score 65.6 (43.8–100.0) 56.3 (18.8–71.9) 0.007
Psychosocial summary score 67.5 (52.5–97.5) 62.5 (17.5–91.7) 0.089
Emotional summary score 65.0 (40.0–95.0) 65.0 (20.0–100.0) 0.401
Social summary score 75.0 (45.0–95.0) 65.0 (5.0–100.0) 0.043
School summary score 55.0 (10.0–100.0) 45.0 (35.0–80.0) 0.666
Cancer-specific scores
Pain and hurt 62.5 (25.0–100.0) 50.0 (12.5–100.0) 0.203
Nausea 70.0 (40.0–100.0) 60.0 (40.0–100.0) 0.554
Procedural anxiety 50.0 (0.0–100.0) 75.0 (0.0–100.0) 0.038
Treatment anxiety 75.0 (16.7–100.0) 83.3 (0.0–100.0) 0.362
Cancer Therapy

Worry 100.0 (33.3–100.0) 75.0 (0.0–100.0) 0.142

Physical appearance problems 100.0 (41.7–100.0) 58.3 (8.3–100.0) 0.008
Communication problems 75.0 (8.3–100.0) 75.0 (41.7–100.0) 0.109
Cognitive problems 62.5 (25.0–100.0) 65.0 (25.0–100.0) 0.226
1
All scores represent median (95% confidence intervals). 2Only children enrolled from BC Children’s Hospital, CancerCare Manitoba, Children’s
Hospital of Eastern Ontario and The Hospital for Sick Children were included in this analysis.

treatment preceding maintenance and during maintenance Discussion

therapy. For patients receiving treatment phases preceding
maintenance therapy, all cancer-specific module items were
qualitatively worse in high-risk patients. More specifically,
pain, nausea, worry, physical appearance and cognitive prob-
lems were significantly worse in high-risk patients. Con-
versely, during maintenance therapy, only procedural anxiety
and physical appearance problems were significantly worse in
high-risk patient compared to standard-risk patients.
We have described QoL for 206 children with ALL in first
remission during active treatment. Relative to healthy chil-
dren, scores from our cohort were lower. More specifically,
Varni et al. surveyed 717 healthy children via PedsQL Generic
Core Scales 4.0 proxy-report and mean 6 SD scores were as
follows: overall score 87.61 6 12.33, psychosocial health 86.58
6 12.79, physical health 89.32 6 16.35, emotional functioning
82.64 6 17.54, social functioning 91.56 6 14.20 and school

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Sung et al.
functioning 85.47 6 17.61.6 Consequently, our median QoL
scores were one to two standard deviations below the healthy
population for all summary scores and dimensions. Our find-
ings are concordant with others who have found that QoL
scores are lower in children receiving treatment for ALL com-
pared to children with ALL
12 months off therapy13 and
lower compared to healthy children.14–16 These findings are
also concordant with qualitative studies of children receiving
treatment for ALL that have noted problems with fatigue, det-
rimental effects of disease and treatment on physical activities
as well as difficulties with social interactions.17,18
Our second objective was to describe predictors of poor
QoL during treatment for nonrelapsed ALL. Little previous
work has focused on identifying children with ALL who have
poor QoL apart from some reports that have explored whether
dexamethasone is associated with worse QoL; these results have
been conflicting.19,20 We found that in general, for high-risk
ALL, older children and girls had worse QoL, whereas for
standard risk ALL, those living in households with lower
incomes and unmarried parents had worse QoL across several
dimensions. Although age and gender are clinically intuitive
predictors of QoL, our work remains important because few
studies have demonstrated such associations,17 and it is impor-
tant to quantify their magnitude. Our association between
lower household income and worse QoL is novel in the setting
of pediatric ALL. Together, different predictors of QoL in
standard- and high-risk ALL suggests that different strategies
to optimize QoL are needed in different ALL risk groups. We
also found that social functioning worsened over time. This
finding is not intuitive because children on maintenance ther-
apy should be integrating better into the school environment
over time. Further research is warranted to determine whether
this finding is replicated in other studies and if so, whether
interventions could be targeted to improve social functioning.
Our third objective was to describe how QoL changes dur-
ing different phases of therapy. Interestingly, we found very
similar QoL scores across different phases for many aspects of
QoL. A study that measured QoL for children treated on the
Dutch ALL-9 protocol evaluated QoL 12 months after initial
diagnosis and at the end of the 2-year treatment.19 Our study
demonstrated that pain, cognitive function, emotion/behavior
and physical function deteriorated between these two time
periods. In contrast, many clinicians would find both of these
observations counterintuitive, because children during mainte-
nance chemotherapy appear much better compared to those
undergoing earlier phases of therapy. One study that supports
clinical intuition included children treated according to the
United Kingdom protocol UKALL 99, and mothers rated their
child’s QoL 3 months after diagnosis and 1 year later.20 Our
study found that physical and emotional functioning improved
over time, whereas there was no change in social functioning.
A second study conducted in the developing country of Indo-
nesia also had similar findings.21 Our study described guard-
ian-reported QoL as assessed using the PedsQL 4.0 Generic
Core Scales and 3.0 Cancer Modules in 98 patients with ALL.
Int. J. Cancer: 128, 1213–1220 (2011) V
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1219
The children were treated with two dexamethasone-based pro-
tocols named the Wijaya Kusuma and Indonesia ALL proto-
cols. In direct contrast to our results, they found that all
aspects of QoL by the generic PedsQL were better during
maintenance therapy compared to phases preceding mainte-
nance. They also found that pain and hurt, procedural anxiety
and communication were better during maintenance phases of
treatment compared to phases preceding maintenance.21 There
are several possible explanations for these discrepancies. First,
it is possible that the generic PedsQL is insufficiently sensitive
to the aspects of QoL that clinicians identify as changing dur-
ing different phases of ALL therapy. Second, it is likely that
patterns of QoL will differ depending on the specific therapeu-
tic protocol and perhaps cultural setting. Third, given the
cross-sectional and not longitudinal nature of our study, it is
possible that our results are affected by confounders.
The strength of our report is the large number of children
receiving active treatment for ALL, and to our knowledge, our
report is the largest study to date. Other strengths are the
measurement of QoL from children treated on high- and
standard-risk protocols and measurement at different points
in therapy as well as the inclusion of children from multiple
different centers. These factors increase the generalizability of
our findings. In addition, this variability allows us to examine
these factors as predictors of QoL.
However, the inclusion of children treated with heterogene-
ous therapy limits our ability to relate QoL to specific chemo-
therapeutic agents. In addition, our study is limited because
only parents of children with ALL who could read English were
included. Another limitation of our report is that we only
measured QoL from the parents’ perspective. However, child
self-report for the PedsQL is only available for children aged 5
years and older, and about 34% of our cohort was younger
than 5 years. In addition, as emphasized by Pickard et al., infor-
mation from multiple sources provides valuable input and the
viewpoint of others regarding child QoL is important in addi-
tion to the opinions of the index child.2 Upton et al. recently
performed a systematic review of pediatric QoL in relation to
Cancer Therapy
parent–child agreement. Our study found agreement ranged
from poor to good depending on the instrument and subscale
and was unable to determine whether agreement is better for
some measures than others.22 Finally, other major limitations
of our study are the cross-sectional design, which precludes de-
finitive assessment of how QoL changes over time within a
child, and the lack of data points after completion of therapy.
In conclusion, we have described QoL in a large cohort of
children with ALL and found that age and gender predicted
QoL in high-risk ALL whereas socioeconomics predicted
QoL in standard-risk ALL. Future efforts should focus on
longitudinal studies that describe QoL over time within indi-
vidual patients both during and after completion of therapy.
Acknowledgements
A.K. and L.S. are supported by New Investigator Awards with the Canadian
Institutes of Health Research.
 1220
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