Pediatr Blood Cancer 2011;57:105–109

Health-Related Quality of Life (HRQOL) Among Pediatric LeukemiaPatients in Malaysia

Alias Hamidah, MD,1* Chee-Yeng Wong, MBBS,1 Azmi M. Tamil, MD,2 Latiff A. Zarina, MD,1

Zakaria S. Zulkifli, PhD,1 and Rahman Jamal, PhD1

INTRODUCTION

As the cure rates for childhood leukemia improve, health-

related quality of life has become an increasingly important out-

come of clinical trials. To measure the health-related quality of

life, the Pediatric Quality of Life Inventory (PedsQL) has been

developed for use in diverse pediatric populations including can-

cer patients [1]. The PedsQL Measurement Model integrates both

generic core scales and disease specific modules into 1 measure-

ment system. There is a version for children and one for proxies

(parents, caregivers). For pediatric cancer patients, imperfect con-

cordance between child self-reports and parent proxy-reports has

been documented previously [2]. Eiser et al. [3] reported that

although correlations between mother and survivor ratings were

usually moderate to good, further analyses showed that mothers

tended to report QOL to be worse than the survivors themselves.

Waters et al. [4] found that children with acute lymphoblastic

leukemia (ALL) have significantly poorer social, physical, and

emotional health and well-being than their healthy peers. Sung

et al. [5] reported that physical, emotional, and social QOL in

children on treatment for cancer were influenced by demographic,

diagnostic, and treatment variables. Only a few studies concerning

HRQOL in pediatric cancer patients have been conducted in

developing countries [6]. Until recently, there were very few

pediatric experts in treating childhood leukemia in Malaysia,

and they had to cope with limited resources including supportive

care. However, with improved resources and better parental

understanding of the need for chemotherapy for their child’s acute

leukemia, more children are receiving and completing treatment.

As cure rates improve, it has become progressively more import-

ant to assess the patient’s HRQOL and overall well-being. We

conducted a study on HRQOL among our patients with the fol-

lowing objectives: (1) to determine the HRQOL in children with

acute leukemia, (2) to compare the HRQOL scores between

children on maintenance chemotherapy and those who were

off-treatment, and (3) to evaluate factors that might be associated

with HRQOL scores.

MATERIALS AND METHODS

The subjects in the study were 77 children aged 2–18 years,

who had been diagnosed with acute leukemia and who were

referred to the pediatric oncology center at the National Univer-

sity Hospital Kuala Lumpur, Malaysia. The 77 children visited the

clinic, daycare, or ward between January 1, 2005 and June 30,

2006, and were invited to participate in the study. The subjects

were on maintenance chemotherapy or were off-treatment and all

were in remission. Off-treatment status was defined as patients for

whom all therapy was completed by the time of assessment.

Children with relapsed leukemia, Down syndrome, or a concom-

itant chronic illness were excluded from the study. The University

institutional review board approved the study that used a struc-

tured questionnaire-survey form in English, Bahasa Malaysia

(the national language of Malaysia), and Mandarin. A validation

of the questionnaire in Bahasa Malaysia and Mandarin which

were translated from the original English version was made by

reverse translation. The questionnaire was reviewed by the mem-

bers of the research team for content validity and was pilot tested

on 10 patients who were part of the research subjects. All eligible

patients enrolled onto the study were approached by one

Background. Health-Related Quality of Life (HRQOL) inpediatric leukemia patients in Malaysia has not been studied before.This was mainly due to a lack of databases on patients in the past.Many patients abandoned treatment or were lost to follow up. Withmore children now fully compliant and completing treatmentnowadays, with higher cure rate, HRQOL has become importantfor our patients. The purpose of the current study was to determinethe HRQOL scores in children with acute leukemia and to comparethe scores for those on maintenance chemotherapy with those off-treatment as well as to determine factors which might affectHRQOL. Methods. Seventy-seven children in a pediatric oncologycenter in Kuala Lumpur, Malaysia diagnosed with acute leukemiawere consecutively enrolled, of whom 22 were on maintenancechemotherapy and 55 off-treatment. The Pediatric Quality of Life

Inventory (PedsQLTM) Scales were used to assess HRQOL. Results.Children on maintenance chemotherapy had significantly lowerchild self-report HRQOL scores across all domains (P < 0.001)especially psychosocial health compared with those who wereoff-treatment. Also, parents with children on maintenance chemo-therapy reported significantly lower HRQOL scores across alldomains (P < 0.05) except social functioning compared withparents with children off-treatment. Younger child age was associ-ated with lower parent proxy-report total score (P ¼ 0.007)Conclusions. Pediatric acute leukemia patients on maintenancechemotherapy experienced significantly poorer HRQOL comparedto those off-treatment. Pediatr Blood Cancer 2011;57:105–109.� 2011 Wiley-Liss, Inc.

Key words: acute leukemia; health-related; Malaysia; quality of life

1Faculty of Medicine, Department of Pediatrics, National University

of Malaysia, Kuala Lumpur, Malaysia; 2Faculty of Medicine,

Department of Public Health, National University of Malaysia, Kuala

Lumpur, Malaysia

Grant sponsor: Faculty of Medicine, National University of Malaysia;

Grant number: FF-173-2004.

Conflict of interest: Nothing to declare.

*Correspondence to: Alias Hamidah, MD, Faculty of Medicine,

Department of Pediatrics, National University of Malaysia, Hospital

UKM, 56000 Cheras, Kuala Lumpur, Malaysia.

E-mail: midalias@ppukm.ukm.my

Received 7 December 2009; Accepted 17 February 2011

� 2011 Wiley-Liss, Inc.DOI 10.1002/pbc.23125Published online 4 April 2011 in Wiley Online Library(wileyonlinelibrary.com).

investigator (C.Y.W.). Written informed consent was obtained

from (one of) the parents.

Measures

The PedsQLTM 4.0 (Pediatric Quality of Life Inventory

Version 4.0) Generic Core Scale is a widely used instrument that

assesses Physical Functioning (8 items), Emotional Functioning

(5 items), Social Functioning (5 items), and School Functioning

(5 items) [7]. It is a modular instrument for measuring HRQOL in

children and adolescents aged 2–18. The Generic Core Scales are

comprised of parallel child self-report and parent proxy-report

formats. Child self-report includes ages 5–7 years (young child),

ages 8–12 (child), and ages 13–18 years (adolescent). Parent

proxy-report includes ages 2–4 years (toddler), 5–7 years (young

child), ages 8–12 (child), and ages 13–18 years (adolescent). The

parent proxy-report forms are designed to assess the parent’s

perceptions of their child’s HRQOL. The items for each of the

forms are essentially identical, differing in developmentally

appropriate language, and worded in the first or third person

[7]. The instructions ask how much of a problem each item has

been during the past 1 month. Item-level and scale-level measure-

ment properties were then computed.

Statistics

Sample size calculations (significant difference of 10 absolute

points in the PedsQLTM 4.0 between the 2 groups) suggested that

the study needed to obtain 36 responses in each arm to be able to

compare the HRQOL scores. Recalculation of the study power

was done in view of the fact that the number of responses col-

lected did not reach 36. The study was conducted with 22 children

on maintenance chemotherapy and 55 children off-treatment

(ratio of 0.4). The true difference of PedsQL 4.0 Generic Scales

in the off-treatment and on maintenance chemotherapy mean was

10.77 with a standard deviation of 12.79. With a significance level

(alpha) of 0.05, the calculated power of this study was 90.9%.

Statistical analyses were conducted using the Statistical Package

for Social Studies (SPSS for Windows Version 11.5; SPSS, Inc.,

Chicago, IL).

RESULTS

Patient Characteristics

A total of 80 patients were approached for the study and all

consented. We received completed questionnaires back from 77

patients, giving an overall response rate of 96%. Of the 77

patients, 22 were on maintenance chemotherapy and 55 were

off-treatment. There was a non-significant difference in mean

child’s age at evaluation between the two groups for the patient

self-report (mean age: on maintenance 8.7 � 2.6 years, range

5–14 years; off-treatment 10.4 � 3.2 years, range 6–17 years).

However, there was a significant difference in age at evaluation

between the two groups in parent proxy-report (mean age: on

maintenance 7.6 � 2.9 years, range 4–14 years; off-treatment

10.2 � 3.3 years, range 4–17 years). We found that the mean

time off-treatment was 35.5 � 28.2 months, range 1–113 months

in the child self-report group and 34.6 � 28.2 months, range 1–

113 months in the parent proxy-report group. The demographic

and clinical characteristics of the children with acute leukemia are

shown in Table I. Two parents did not complete items for the

parent proxy-report Emotional Functioning Scale, and five parents

did not complete items for parent proxy-report School Function-

ing Scale.

Quality of Life measurement

Most self-report scales and proxy-report scales approached or

exceeded the minimum reliability standard of 0.70. A total of 69

questionnaires on child self-report were analyzed. We excluded

child self-report data for eight patients, including four who were

2–4 years old, and four who were between 5 and 7 years, but not

yet able to comprehend the questionnaire. In order to determine

TABLE I. Demographic and Clinical Characteristics of the

Children With Acute Leukemia

n (%)

Age group (years)

2–4.9 4 (5.2)

5–7.9 22 (28.6)

8–12.9 36 (46.7)

13–18 15 (19.5)

Gender

Male 44 (57.1)

Female 33 (42.9)

Ethnicity

Malay 56 (72.7)

Chinese 13 (16.9)

Indian 7 (9.1)

Others 1 (1.3)

Diagnosis

ALL 73 (94.8)

AML 4 (5.2)

Treatment status

Maintenance therapy 22 (28.6)

Off-treatment 55 (71.4)

Child education

Not schooling 15 (19.5)

Primary 49 (63.6)

Secondary 13 (16.9)

Parents education

Father (n ¼ 71)a

Primary 6 (8.4)

Secondary 47 (66.2)

Diploma 8 (11.3)

Degree 10 (14.1)

Mother (n ¼ 74)b

Primary 8 (10.8)

Secondary 49 (66.2)

Diploma 12 (16.2)

Degree 5 (6.8)

Household income, RM (n ¼ 75)c

<999 14 (18.7)

1,000–1,999 15 (20.0)

2,000–2,999 12 (16.0)

3,000–3,999 9 (12.0)

>4,000 25 (33.3)

ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia;

RM, Ringgit Malaysia. aThree information not given, two had

divorced and separated from child, and one has died; bThree infor-

mation not given; cTwo information not given.

106 Hamidah et al.

Pediatr Blood Cancer DOI 10.1002/pbc

differences in QOL scores between the in-treatment group and the

follow-up group, an independent t-test was conducted. There was

a significant difference between children with acute leukemia on

maintenance versus those off-treatment in overall HRQOL scores

(Table II). A significantly lower mean summary score in all

domains and a lower mean Total Scale Score were observed in

children who were on maintenance chemotherapy compared with

those off-treatment (Table II). The magnitude of the differences

was significant as the effect sizes were >1.0.

For the parent proxy-reports, we found that the HRQOL scores

were lower in all domains for children who were on maintenance

chemotherapy compared to those off-treatment (Table III). The

effect size was large in total score (0.85), physical health (0.79),

emotional functioning (0.85), and school functioning (0.86). The

effect size was moderate in psychosocial summary health (0.65)

and social functioning (0.41). We found a moderate to good

agreement between parents and child ratings in all subscales

(Table IV) according to guidelines established by Cohen and

Holliday [8].

There was no significant difference between ethnic groups

Malay versus Chinese versus others for all domains for both

child-self report and parent proxy-report. There was no associ-

ation between child total scale score and age of child (P ¼ 0.13),

child’s education (P ¼ 0.52), father’s education (P ¼ 0.75),

mother’s education (P ¼ 0.62), and total parental income

(P ¼ 0.20). In the parent proxy-report there was however a sig-

nificant association for total scale score and the age of the child

(P ¼ 0.007).

DISCUSSION

Children with cancer while on-treatment in a high income

country have been reported to experience more HRQOL problems

than those off-treatment [1]. In this study in Malaysia (a devel-

oping country), we found that children with acute leukemia on

maintenance chemotherapy did also experience more problems

than those who were off-treatment. The significantly lower mean

summary scores in children on maintenance chemotherapy could

be explained by many factors. Apart from lingering anxiety about

future health and worries about complications such as neutropenic

fever or relapse, cultural differences in this multi-ethnic popu-

lation could influence QOL. In general, children in many South-

east Asian countries are rather shy about expressing many aspects

of their feelings openly. The Malays are considered relatively

shyer than the Chinese and Indian. However we did not find

any significant differences between ethnic groups for both child-

self report and parent proxy-report in this study. In addition,

worries about being isolated by friends at school and being

restricted in sports activities imposed by parents and teachers

could be contributing factors. Lower mean summary scores were

also observed in the parent proxy-report with children on main-

tenance chemotherapy. Factors related to family issues for

TABLE III. PedsQL 4.0 Generic Core Scalesa for Children With Leukemia on Maintenance Therapy and Off-Treatment

PedsQL 4.0 Generic Core Scales Maintenance therapy (n ¼ 22), mean � SD Off-treatment (n ¼ 55), mean � SD P-Value

Total score 73.21 � 13.60 83.98 � 12.46 0.001

Physical summary health 75.31 � 19.25 88.33 � 15.68 0.008

Psychosocial summary health 72.89 � 14.69 81.61 � 13.24 0.013

Emotional functioningb 69.09 � 15.93 82.26 � 15.61 0.001

Social functioning 82.73 � 18.82 89.04 � 14.40 0.117

School functioningc 61.94 � 19.11 73.70 � 18.46 0.023

n, number; SD, standard deviation. aParent proxy-report version; bMaintenance therapy, n ¼ 22, off-treatment, n ¼ 53; cMaintenance therapy,

n ¼ 18, off-treatment, n ¼ 54.

TABLE II. PedsQL 4.0 Generic Core Scalesa for Children With Leukemia on Maintenance Therapy and Off-Treatment

PedsQL 4.0 Generic Core Scales Maintenance therapy (n ¼ 16), mean � SD Off-treatment (n ¼ 53), mean � SD P-Value

Total score 68.48 � 13.51 85.26 � 9.91 <0.0005

Physical summary health 73.83 � 16.80 89.09 � 12.59 <0.0005

Psychosocial summary health 65.63 � 13.66 83.00 � 11.22 <0.0005

Emotional functioning 62.19 � 21.91 82.96 � 17.00 <0.0005

Social functioning 75.31 � 15.33 89.72 � 11.33 <0.0005

School functioning 59.38 � 17.11 76.35 � 17.35 <0.001

n, number; SD, standard deviation. aChild self-report version.

TABLE IV. Concordance Between Child Self-Report and Parent

Proxy-Report PedsQOL Scores

Subscale Correlation co-efficient P-Value

Total score 0.66 (G) <0.0005

Physical summary health 0.55 (G) <0.0005

Psychosocial summary health 0.62 (G) <0.0005

Emotional functioning 0.61 (G) <0.0005

Social functioning 0.38 (M) 0.001

School functioning 0.53 (G) <0.0005

M, medium; G, good.

Quality of Life in Pediatric Acute Leukemia in Malaysia 107

Pediatr Blood Cancer DOI 10.1002/pbc

examples having another sibling with a chronic illness or looking

after old grandparents in the same house or societal attitudes to

illness could increase stress levels for parents of a child with acute

leukemia, hence affecting QOL. We found that a lower mean

score was most prominent in the school functioning subscale

for children with acute leukemia on maintenance chemotherapy,

both in the child self-report and in the parent proxy-report. This

may be caused by frequent school absences as a result of clinic

follow-up, hospitalization due to treatment-related complications

such as febrile neutropenia, and by restriction of social activities

for fear of acquiring infections.

Our analysis found that the agreement between parents and

child ratings was moderate to good in all subscales (Table IV).

However, the children reported greater improvement off-treatment

compared with the period of maintenance chemotherapy than did

the reports of their parents. However, although not statistically

significant, children on maintenance chemotherapy appeared to

report poorer scores in all domains than parents. This finding is in

contrast to a previous report in a Western Country, where mothers

of children with ALL rated low QOL scores compared with

population norms [4]. Our study findings give a better understand-

ing of the relationship between children and parents reporting as

we studied responses of children and their parents in two different

situations: during maintenance and off-treatment. We found that

parents of children who were off-treatment reported lower mean

scores in all domains than the children themselves. This supports

the importance of including child self-reports whenever feasible.

In a literature review by Varni et al. [9] it is recommended that a

child self-report be used in children as young as 5 years old if

they can reliably and validly report their HRQOL. Another

analysis came to the same recommendation [10]. Considerable

differences can occur between child and parent ratings of QOL.

Parent proxy-reports remain useful when patients are too young,

too cognitively impaired, or too ill or fatigued to complete a

HRQOL instrument [9]. But the parent proxy-reports are also

very valuable to evaluate the impact of the child’s disease on their

parents. If it becomes clear that the child itself suffers less than

what the parents perceive, it may help to prevent over-protection

of the children, especially off-treatment.

For those off-treatment, learning difficulties and poor aca-

demic achievement as a result of the late-effects of chemotherapy

might explain lower scores in the school domain [11–13]. A

decline in academic performance more than 3 years after diag-

nosis was reported, and this could explain persistent lower scores

in the school domain [11]. However, we did not find a significant

difference in QOL scores between children who were off-treat-

ment for less or more than 3 years. About 40% of the patients in

the off-treatment group in this study were off-treatment for longer

than 3 years. Administration of craniospinal irradiation as central

nervous system (CNS) directed therapy in leukemia has been

associated with a poorer outcome in assessment on the Wechsler

test [14]. In our study, 20/55 patients had received cranial irradia-

tion. We found that parents reported significantly poorer social

functioning for children who did not receive cranial irradiation

compared to those who received cranial irradiation (mean score:

no cranial irradiation 86.50 þ 16.20; cranial irradiation

93.50 þ 9.33, P ¼ 0.047). We do not have a ready explanation

for this findings, it could be due to the small sample size in our

study.

We found that parents reported significantly lower total QOL

in the younger age group (r ¼ 0.304, P ¼ 0.007). Having a child

affected with acute leukemia at a young age could have caused

parents to worry more about the side effects of treatment and

overall well-being of their child. Previous studies have reported

that ethnicity, gender, sibling, and household characteristics were

also associated with differences in HRQOL [5,15,16]. Our study

did not allow us to fully test these subgroups. Another limitation

of our study was that we sampled patients from one center only.

Our results demonstrate that children with acute leukemia on

maintenance chemotherapy had significantly poorer QOL than

those off-treatment. The children also reported poorer QOL scores

while on maintenance chemotherapy compared to their parents.

Therefore, child self-reports are important to measure HRQOL

whenever feasible. HRQOL test results are valuable for the

pediatric oncology team to pinpoint problem areas and to discuss

these with parents and teachers, to try to achieve the best possible

remediation once patients are off treatment.

ACKNOWLEDGMENT

This study was supported by a research grant (no. FF-173-

2004) from the Faculty of Medicine, National University of

Malaysia. The authors would like to thank Professor J. W. Varni

for the permission to use the PedsQLTM 4.0 (Pediatric Quality of

Life Inventory Version 4.0) Generic Core Scales.

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