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205]

Original
Article

The impact of weight for age on survival in acute

lymphoblastic leukemia: Report from a tertiary care center in
North India
Trehan A, Prabhu V1, Bansal D
Pediatric HematologyOncology Unit, Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research,
1
Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Correspondence to: Dr.Amita Trehan, Email:trehanamita@hotmail.com

Abstract

BACKGROUND: Undernutrition is considered to have a negative impact on survival in children with malignancies. The objective of this retrospective

analysis was to evaluate the morbidity pattern and outcome of therapy in undernourished(UN) children with acute lymphoblastic leukemia.
METHODS: A retrospective analysis of impact of weight for age was performed in children treated for ALL. The IAP & CDC criteria for undernutrition
were used in the two different time periods of analysis. RESULTS: There were two cohorts in the study: Between 1995 and 2005, 360 children were
evaluated where the weight for age was classified using the Indian Academy of Pediatrics criteria for undernourishment(GroupA). GroupB of
the study included 373 children treated from 2007 to 2011, who were graded as per the Centers for Disease Control criteria for weight for age. In
GroupA, 35% of the children were malnourished at presentation. The morbidity and supportive care needed in the wellnourished and UN group were
similar. The eventfree survival and mortality were similar in both groups. Analysis of GroupB showed an overall survival of 62.6% with a greater
survival in children with a weight of10thcentile for age compared to children at the<10thcentile,(P=0.026) with a higher mortality(P=0.011)
in the UN group. CONCLUSION: Our data have yielded conflicting results. The older cohort did not show a significant difference in survival using
malnutrition as a risk factor. However, in the subsequent cohort, a difference in survival was noted. This could be due to the reason that different
criteria for classification of undernutrition were applied in the two groups. This analysis lays the foundation for a future prospective analysis to
evaluate nutrition as an independent risk factor nutrition as an independent risk factor in the outcome of childhood malignancies.
Key Words: Acute lymphoblastic leukemia, survival, undernutrition

We are guilty of many errors and many faults, but our

worst crime is abandoning the children, neglecting the
foundation of life. Many of the things we need can wait.
The child cannot. Right now is the time his bones are being
formed, his blood is being made and his senses are being
developed.
To him we cannot answer Tomorrow. His name is Today.
Gabriela Mistral, 1948.
Introduction
The progress made in the outcome of childhood acute
lymphoblastic leukemia(ALL) has been remarkable. Current
literature from the developed countries reports eventfree
survival(EFS) of about 75% and overall survival(OS)
of about 90%. However, more than 80% of the worlds
children live in lessadvantaged countries, where the cure
rate generally does not exceed 35%.[1,2] There are various
factors for this incomparably low cure rate in the developing
countries with numerous reasons being cited.[35] Patients
with ALL in the developing countries often present with
more advanced disease. Comorbidities such as hepatitis,
malaria, and malnourishment are also considered to affect
patients ability to tolerate treatment. Ethnic factors, biology
of the malignancy, and altered drug mechanisms have also
been considered to play a role in the outcome.[35] Most
developing countries face an inadequacy of health care
facilities with access to care in cancer centers or pediatric
oncology units being limited. Continuation of treatment
and followup is often difficult because of socioeconomic,
cultural, and demographic factors.
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Undernutrition is considered to be an adverse prognostic

factor in the outcome of treatment in patients with ALL,
influencing the course of the disease and the chances of
survival. [36] The relationship between malnutrition and
poor prognosis of patients with ALL is possibly due to
diminished bone marrow reserve in these children resulting
in lower than optimal doses of socalled maintenance
chemotherapy, with subsequent higher relapses. [37] The
prevalence of malnutrition in India in children is 45.9%
as per the National Family Health Survey(NFHS)
of India 3(20062007). [8] As per the World Health
Organization(WHO), 1/3rdof the worlds malnourished
children are from India.[9] The 2011 report on global hunger
index has India at a rank of 15. Our study was designed to
systematically analyze the prevalence and severity of poor
nutrition in children with ALL presenting to our center and
to evaluate the morbidity pattern and outcome of therapy
in undernourished(UN) children and wellnourished(WN)
children.
Materials and Methods
This retrospective study was carried out in the
HematologyOncology Unit of the Advanced Pediatric
Centre. Data were retrieved from the case records of
pediatric oncology clinic files. Children who were started
on treatment from January 1, 1995, to December 30, 2011,
were the subjects in the study. We have taken weight for age
as criteria for nourishment.
This is an open access article distributed under the terms of the Creative Commons
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tweak, and build upon the work noncommercially, as long as the author is credited
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How to cite this article: Trehan A, Prabhu V, Bansal D. The

impact of weight for age on survival in acute lymphoblastic
leukemia: Report from a tertiary care center in North India. Indian J
Cancer 2015;52:203-6.

203

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Trehan, etal.: Outcome in undernourished children with ALL

All children were treated as per the guidelines of UKALL

X(19952005) and UKALL 2003 protocol (20072011).
All children who opted for treatment for ALL were
analyzed. Weight and height of the child at diagnosis were
recorded in the case record files. This study was done in
phases. In the first half of the study, the Indian Academy of
Pediatrics(IAP) classification(weight for age: >81stcentile:
WN; 7180% expected weightGrade1 undernutrition;
6170% expected weightGradeII undernutrition; <60%
expected weightGradeIII undernutrition) was used for
the definition of undernutrition(January 1995 to December
2005).[10] In the analysis, this subgroup is referred to as
GroupA. In this analysis, details pertaining to episodes
of febrile neutropenia, death, need for platelet, and blood
transfusions were recorded on a predesigned proforma. From
2007 onward, the weight was compared with the Centers
for Disease Control(CDC) normative data for the definition
of malnutrition.[11] Analysis was restricted to survival. This
cohort was referred to as GroupB. Children treated in 2006
were not analyzed due to logistic reasons. For the purpose
of analysis, children<10thcentile were taken as UN while
the rest of the children 10thcentile were classified as the
WN set in GroupB.
Statistical analysis

SPSS software version17(IBM Statistical Package for Social

Sciences Chicago, IL, USA) was used for analysis:
The mean and standard deviation (SD) of all quantitative
parameters were calculated
Percent occurrence rate (frequency) in respect of different
morbidities experienced by the sample subjects was
calculated. Chisquare test was applied to quantify the
extent of intergroup(WN vs. UN) differences
Analysis of disease outcome was examined as OS and
EFS. OS was measured from the date of initial diagnosis
of ALL to the date of death from any cause or the
date of last contact using the KaplanMeier method.
EFS was defined as the time to first induction failure,
relapse, or death, whichever was earlier. Treatmentrelated
mortality(TRM) was defined as death unrelated to the
primary disease. Association of categorical variables with
the presence of complications or mortality was tested
by Chisquare test. Odds ratios with 95% confidence
interval(CI) were calculated.
Results
Our analysis is based on the weight for age of the child
when diagnosed with leukemia. In cohort named as
GroupA, 360 children received therapy between January
1995 and December 2005. The mean age at presentation
was 5.83.1years(range 0.613.5years). Three
hundred and twenty one(89%) children were<10years
of age and 39(10.8%) were>10years of age[Table1].
In this group, as per the IAP classification, 125(34.7%)
were UN. Seventythree(20.27%) had GradeI
malnutrition, 43(11.9%) had GradeII malnutrition,
and 9(2.5%) had GradeIII malnutrition. The mean
number of admissions during treatment in the WN
group was 3.42.196(range 014). The mean
number of admissions during treatment in the UN
204

group was 3.181.784(range 08)(P=0.561).

The number of episodes of febrile neutropenia,
admissions, blood and platelet transfusions is enumerated
in Table2. The Pvalue for the morbidities between
the two groups was not significant(0.412 for febrile
neutropenia, 0.73 for blood transfusion, 0.866 for
platelet transfusions, and 0.388 for postponement of
therapy). In the analysis, 160(44.4%) children are
survivors, 95(27.7%) relapsed, 67(18.6%) died, and
38(10.6%) defaulted treatment. The survival, relapse,
and death which were similar between the WN and the
UN children is shown in Table3. The difference in the
status between the WN and the UN was not statistically
significant(P=0.63). The estimated diseasefree survival
in the WN children was 2037.776114.942days(CI
1812.4892263.063days) and in the UN children it was
2135.918168.063days(CI 1806.5142465.332) with
no statistical difference(P=0.829).
A total of 373 children with ALL treated between January
2007 and December 2011 were analyzed for the effect of
a poor nutritional status on outcome. This group is called
GroupB. The mean age was 5.92.9years(113).
The male:female ratio was 2.5:1. The CDC criterion was
used for classification of weight centiles in this cohort of
patients[Table1]. Fiftythree percent of children had a
weight, which was equal to or less than the 5thcentile as
per CDC criteria. There were only 24 children in the whole
cohort whose weight was>75thcentile. The ratio of WN
verses poorly nourished children did not differ between
high risk and standard risk ALL(as per the National
Cancer Institute criteria). We compared deaths and events
between the children who had a weight of<10thcentile
with those who had a weight of10 th centile. The
difference in OS was significant(1579.52days[95%
CI 14191740] vs. 1894.6days[95% CI
17342055.2][P=0.026])[Figure1]. The EFS
was also greater in children who had a weight
of 10thcentile(1718.86days[95% CI 15471890] and
1420.34days[95% CI 12621577][P=0.022]). TRM was
higher in the group with a weight of<10thcentile compared
to children who had a weight of10thcentile(P=0.011).
The relapse rates in both groups were similar(12.7% in the
groups with a weight of10thcentile and 16.6% in the
group with a weight of<10thcentile; P=0.109).
Table1: Demographics of children with acute
lymphoblastic leukemia
1995-2005 (Group A) 2007-2011 (Group B)
Number of children
Mean age(years)
Male:female

360
5.8(0.6-13.5)
285:75

IAP

373
5.9(1-13)
267:106

Percentage CDC(centile) Percentage

Nutritional status WN
Grade I
Grade II

65.3
20.3
11.9

>95th
2575th
10th

2.0
21.7
16

Grade III

2.5

5th

23.4

<5

29.7

th

WN=Wellnourished; IAP=Indian Academy of Pediatrics; CDC=Centers for Disease

control

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Trehan, etal.: Outcome in undernourished children with ALL

Table2: Morbidity pattern of the wellnourished and undernourished group(Group A)

Group

Total admissions
meanSD(range)

Blood
transfusions

Platelet
transfusions

Febrile
neutropenia

WN(n=235)
UN(n=125)

3.402.196(0-14)

1.311.707(0-10)

0.461.261(0-11)

1.611.778(0-8)

3.181.784(0-8)

1.281.579(0-10)

0.461.081(0-6)

2.01.308(0-7)

WN=Wellnourished; UN=Undernourished; SD=Standard deviation

Table3: Status of children after therapy

Nutritional
status
WN(n=235)
UN(n=125)
Group I(73)
Group II(43)

Status
Well

Relapsed

Died

105(44.7)
55(44)
31(42.5)
20(46.5)

66(28.1)
29(23.2)
18(24.7)
10(23.3)

45(19.1)
22(17.6)
12(16.4)
7(16.3)

1(11.1)

3(33.3)

Group III(9) 4(44.4)

Total

Defaulter
19(8.1) 235 0.635
19(15.2) 125
12(16.4) 73
6(14.0) 43
1(11.1)

WN=Wellnourished; UN=Undernourished

Figure 1: Survival on Group B

Discussion
Malnutrition is found in 1050% of children with cancer in
resourcecrunched countries.[4,6] Cancerassociated malnutrition
can result from local effects of a tumor, the host response to
the tumor, and anticancer therapies. In addition, depletion
of lipid stores, alteration in carbohydrate metabolism, and
an increased protein turnover are responsible for a poor
nutritional status in cancer patients. Undernutrition also adds
onto the diminished immunity in patients with malignancy.
Drug pharmacokinetics is also considered to be altered based
on differences in the body composition in WN compared
to UN individuals. [12] In lowincome countries, a large
proportion of the normal pediatric population is UN and
children frequently present late with advanced disease. [13]
Undernutrition in young children is a substantial problem
in India. Accordingly to NFHS3, in 20052006, 46%
of children<3years of age were underweight, 38% were
stunted, and 10% were wasted. The proportion of children
who are severely UN is also notable24% are severely
stunted and 16% are severely underweight. The figure is not
different in North India with Punjab having a 37% incidence
of malnutrition in the<5year age group.[8]
Many studies show that there exists a relationship between
undernutrition and poor prognosis in children being treated
for malignancy. However, there are conflicting results as
Indian Journal of Cancer | April-June 2015 | Volume 52 | Issue 2

to the outcome in malnourished children with cancer.

LobatoMendizbal in their review of published literature
on 1123 children reported the relative risk of dying to be
1.8times greater in UN children and have opined that
undernutrition may be an independent prognostic factor in
the longterm outcome of cancer patients. The correlation
between malnutrition and compromised treatment was 0.92.[14]
Viana et al. have reported the outcome to be 59% in the
WN group in comparison to 27% in the UN group.[7] Sala
et al. in their analysis of malnutrition in cancer in a cohort of
2954 children in Central America reported 45% children to be
severely depleted as per the criteria of midarm circumference.
They found poor nutrition to correlate with higher mortality
and increased abandonment. In addition, the EFS was 65% in
the WN children in comparison to 48% in the UN group.[5]
Antillon in 2013 has reported 41.5% patients to have severe
nutritional depletion with a 2.4times greater risk of dying.[15]
RiveraLuna etal. in a multivariate analysis did not find
undernutrition to correlate to a poor outcome.[16] A study
done in Cuba did not show any difference in outcome related
to malnutrition.[17] Closer home, a study published from
Lahore failed to demonstrate the effect of malnutrition on the
outcome in children with ALL.[18] In the UnitedKingdom,
body mass was seen to have no influence on the outcome
of the disease.[19,20] However, their study was restricted to
relapses rather than survival. Pedrosa et al. in their study from
Brazil and El Salvador also did not see a demonstrable effect
of nutrition on outcome.[21] Studies from India with a limited
cohort have shown malnutrition to have an adverse prognosis
on morbidity and shortterm outcome.[2225]
In GroupA in our study, undernutrition was not
found to have an impact on the outcome of ALL. In
addition, the grade of malnutrition also had no effect
on the outcome. However, the total number of severely
malnourished(GradeIII) children was only nine with
a mortality of 33%. The small number of severely
malnourished children would have probably precluded
statistical significance. The mean albumin of the children
was 3.6380.6161g/dl and did not differ significantly
between the WN and the UN children. The normal serum
albumin levels in UN children despite their weight for age
criteria could explain the comparable levels of outcome in
both the nourishment groups. In addition, malnutrition was
not seen to be associated with increased episodes of febrile
neutropenia, admissions or transfusion requirements in our
study. The overall mortality rates in GroupA of our study
were 18.6% with the mortality rates in the WN and the
UN children being almost equal. In the Indian collaborative
trial, nutritional status was not seen to be a risk factor
influencing outcome and survival.[26] Analysis at a later date
on patients between 2007 and 2011 showed a difference in
outcome between children<10thcentile for age and those
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Trehan, etal.: Outcome in undernourished children with ALL

above 10thcentile as per the CDC criteria,(EFS: 57.1% vs.

69.6%; P=0.004)[Figure1], indicating malnutrition to
be an independent criteria for the outcome of ALL. TRM
was significantly higher in the UN group(P=0.011). We
have conflicting results in relation to the nutritional status
at diagnosis in our own data. We would attribute this to
the different norms used in the two groups analyzed(IAP
and CDC) as the population demographics remain similar.
As per the CDC criteria, we found nearly 30% of children
to be below the 5thcentile and 53% children were at and
below the 10thcentile. In contrast, in the cohort classified
as per the IAP criteria, only 2.5% children had severe
malnutrition.
The need for assessment of nutrition in a child with
cancer cannot be overemphasized. We have used weight
for age as the parameter for assessment. There is no gold
standard for nutritional assessment. Most studies have been
retrospective and have used weight for age as well as SD
scores for weight for age, height for age, and weight for
height.[6,14,18,20,24] Studies range from having only ALL in
the cohort and a mixed population of tumors. Moreover, all
growth charts have fallacies with none being described as
optimal in a particular setting. WHO charts till recently
were for children till 5years of age and the CDC charts
reflect a shorter and heavier sample. Most pediatricians in
our country would use the charts recommended by the IAP
compiled by Agarwal and Agarwal.[10,27] Weight for age is
reasonably sensitive in assessing children who do not have
a solid tumor.
This study is confined being a retrospective analysis with
limited available information to further classify nutritional
status. Studies across the globe have used varying criteria
for assessment. International society of pediatric oncology
(SIOP)has recommended weight for height with agerelated
cutoff and a midupper arm circumference for a quantitative
assessment of nourishment.[28] A collaborative prospective
study using a common algorithm for assessment is needed
in India to evaluate the magnitude of the problem and to
assess the impact on morbidity and mortality. Moreover,
we need to formulate plans for nutritional intervention and
prevention of malnutrition during therapy in cancer children
to improve the outcome.
Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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