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ORIGINAL ARTICLE
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Nutritional status in children with acute lymphoblastic leukemia, and its correlation with severe infection


 Department of Pediatrics, Division of Hematology Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Date of Submission03-Feb-2019
Date of Decision17-May-2019
Date of Acceptance31-May-2019

Correspondence Address:
Rimjhim Sonowal,
Department of Pediatrics, Division of Hematology Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_110_19

  Abstract 


Background: Undernutrition is a common childhood problem in India which may contribute to higher risk of infection and lower survival rate in children with acute lymphoblastic leukemia (ALL).
Methods: In our study, we retrospectively included patients of age group 1-15 years who were treated for ALL and survived induction. Data on weight, height and serum albumin levels recorded at the time of diagnosis of the patients were used in this study. For defining acute undernutrition we used weight-for-height, weight-for-age criteria for children ≤5 years and body mass index for age >5 years. We correlated nutritional status of the patients with severe infection and mortality percentage.
Results: There were 101 patients with male:female ratio of 2.4:1. Forty-four children were ≤5 years and 57 children were >5 years of age. It was found that 74 children had B-cell ALL and 17 children had T-cell ALL; 54 patients were stratified as high-risk and 47 as standard-risk. In all, 52.5% patients had acute undernutrition at diagnosis. In ALL patients with acute undernutrition, severe infection was found to be 10.8% higher than ALL patients with normal nutrition which was statistically insignificant. Male children and children with serum albumin level <3.5 g/dL in the acute undernutrition group had higher risk of infection. Mortality percentage of patients with baseline acute undernutrition was found to be higher by 11% than normal nutrition group (P-value = 0.21).
Conclusion: Our study highlights the magnitude of undernutrition at diagnosis in ALL patients in a tertiary care centre. It also correlates nutritional status with severe infection and mortality in follow-up.


Keywords: Acute lymphoblastic leukemia, severe infection, undernutrition
Key Message: Nutritional management is as important as chemotherapy for a favorable outcome in treatment of childhood malignancies.



How to cite this URL:
Sonowal R, Gupta V. Nutritional status in children with acute lymphoblastic leukemia, and its correlation with severe infection. Indian J Cancer [Epub ahead of print] [cited 2020 Oct 30]. Available from: https://www.indianjcancer.com/preprintarticle.asp?id=297011





  Introduction Top


Undernutrition is a common problem in developing countries including India and contributes hugely to mortality and morbidity in children. According to National family health survey-4 in India, 36% of children under 5 years of age are underweight, 38% are stunted and 21% are wasted.[1] Acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. There is a dramatic improvement in the 5-year survival rate in children with ALL, which is now more than 80% in developed countries. Lower survival rate of childhood ALL in the developing countries has been related to undernutrition, higher risk of infection, lack of adequate supportive care, and poor compliance to therapy.[2] It is recognized that diminished nutritional status in children with cancer may be a contributing factor for poor immune function, disturbed drug metabolism leading to drug toxicities, and adverse clinical outcome.[3],[4] The proportion of undernourished children with ALL ranges from about 10% in the developed nations[5],[6] to more than 60% in the developing countries.[7],[8]

Our center is a tertiary care center and caters medical services to eastern UP, Bihar and nearby states. Patients from these states usually come from a poor socioeconomic background. Burden of undernutrition in children is high in this part. This poor nutritional state may further be aggravated by presence of diseases including cancer. It may lead to adverse outcome in ALL. Few studies on the nutritional state of children with ALL have been performed in this part of India.

Thus, we undertook this study to assess (a) the prevalence of undernutrition in children with ALL and (b) to observe the correlation of acute undernutrition with severe infection during induction chemotherapy.


  Materials and Methods Top


We obtained data retrospectively from 101 patients of age group 1-15 years, treated for ALL who survived induction in the Department of Pediatrics, Division of Hematology Oncology during the period 2011-2016. Ethical approval was taken from institutional ethics committee. All the patients were diagnosed on the basis of bone marrow examination. Immunophenotyping and multiplex polymerase chain reaction (PCR) was done in majority of them. We stratified patients into standard and high-risk based on age, initial count, central nervous system (CNS) status, immunophenotyping and cytogenetics (where available). Standard-risk patients were given three-drug induction (vincristine, L- asparaginase and prednisolone) and high-risk patients were given four-drug induction (vincristine, L-asparaginase, prednisolone and daunorubicin) according to unit protocol. In each patient, weight and height were recorded at diagnosis. Serum albumin level of patients was assessed at admission. We divided patients into two groups based on age ≤5 years and >5 years, respectively.

World Health Organization (WHO) growth charts and definitions were used to define undernutrition. We have taken moderate and severe undernutrition cases into consideration. Weight-for-age, weight-for-height and body mass index (BMI) values were taken as indicators of acute nutritional status, whereas height-for-age was an indicator of chronic nutritional state.

For patients of age ≤5 years, weight-for-age, weight-for-height and height-for-age less than -2 z-scores below the median of the WHO child growth standards defined undernutrition.

In patients of age >5 years, undernutrition was defined by BMI and height-for-age less than -2 z-scores below median of WHO growth references.

We collected data from medical records maintained in the unit about clinical symptoms and signs, persistent fever, persistent neutropenia, blood culture/fungal culture and urine culture tests, chest x-ray/computed tomography (CT) scan, use of antibiotics, antifungal or antiviral drugs. Patients with severe infection were those patients who had any of these: febrile neutropenia, pneumonia, lung abscess, cellulitis, viral infection or fungal sepsis.

Data about the current status of these patients was collected from database maintained in the Division of Pediatric Hematology Oncology. Also socioeconomic status was recorded. For classifying socioeconomic status modified Kuppuswamy's socioeconomic status scale was used.[9] Mortality percentage was calculated.

Statistics

The data were presented in number and percentage. Chi-square/Fisher's exact probability tests were used to find out the association as per suitability of data, odds ratio (OR) and 95% confidence interval (CI) were calculated. P value <0.05 was taken as statistically significant.


  Results Top


Out of total 101 patients with ALL, 71 were male and 30 female. Male:female ratio was 2.4:1. Moreover, 44 children were of age ≤5 years and 57 children were of age more than 5 years. Immunophenotyping was done in 91 patients of whom 74 had B-cell ALL and 17 had T-cell ALL; 54 patients had high-risk and 47 had standard-risk ALL.

In children of age ≤5 years, undernutrition was present in 25% according to weight-for-height criteria, in 43.1% according to weight-for-age criteria and in 25% patients according to height-for-age criteria. In children of age >5 years, undernutrition was present in 45.6% according to BMI criteria and in 26.3% according to height-for-age criteria. As weight-for-age, weight-for-height and BMI (in >5-year age group) denoted acute malnutrition, 53 out of 101 patients had some form of acute undernutrition (52.5%).

As shown in [Table 1], the presence of severe infection in patients with ALL with undernutrition was higher than those without undernutrition. The observed difference was 10.8% (P-value = 0.24). The percentage of severe infection in ALL patients with undernutrition was higher but statistically insignificant. Febrile neutropenia was the commonest form of infection followed by pneumonia.
Table 1: Prevalence of infection in ALL patients with malnutrition and normal nutrition (n=101)

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We analysed the possibility of infection in ALL patients with acute undernutrition during induction phase of chemotherapy against risk factors of gender, age, serum albumin level, immunophenotype and risk stratification by calculating odds ratio [Table 2]. Male children with acute undernutrition had almost six times higher risk of infection as compared to females which was statistically significant (OR 5.95, 95% CI 1.29-26.43; P = 0.03). Similarly patients with serum albumin level <3.5 g/dL had four times higher risk of infection in comparison to patients with normal serum albumin levels (OR 4.2, 95% CI 1.02-1.81; P = 0.02). Other factors did not show significant association with severe infection. In ALL patients without undernutrition, no such significant association of these factors was found with severe infection [Table 3].
Table 2: Risk factors for infection in undernourished patients with acute lymphoblastic leukemia (ALL) (n=53)

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Table 3: Risk factors for infection in normal nourished patients with acute lymphoblastic leukemia (ALL) (n=48)

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Majority of the patients belonged to lower middle and upper lower class of socioeconomic status scale. It was seen that 3 out of 53 patients with acute undernutrition was lost to follow-up. Among the remaining 50 patients, 13 patients expired. Thus in acute undernutrition group, the mortality percentage after induction phase chemotherapy was 26%. Similarly as shown in [Table 4], in normal nutrition group only one patient was lost to follow-up and mortality percentage was 14.9%. However, the difference of loss to follow-up was statistically insignificant (P-value 0.62). Though the mortality percentage in undernutrition group was higher by 11% than normal nutrition group P value is 0.21, and hence, statistically the difference is not significant.
Table 4: Mortality percentage of patients with acute lymphoblastic leukemia (ALL) after induction phase chemotherapy according to the nutritional status

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  Discussion Top


In our study, 52.5% of ALL patients had acute undernutrition at diagnosis. Our study used WHO growth standards. In a previous study by Kumar et al.,[10] when weight-for-age was taken as criteria for assessing malnutrition, 52% of the patients with ALL had malnutrition. If arm anthropometry was included in addition, the collective prevalence of malnutrition rose to 88%. National Center for Health Statistics (NCHS) standards were used for weight and height. However, in routine clinical practice, weight and height are the most frequently employed anthropometric tools to assess the nutritional status, as it is easy to perform. Skin fold thickness measurement requires Harpenden caliper, which is expensive, requires expertise to handle it and mid-upper arm circumference is reliable only up to the age of 5 years.

In one study by Jain et al.,[11] in children with newly diagnosed malignancy, malnutrition was seen in 56.8% children by weight-for-age criteria. In another study by Tandon et al.,[12] the prevalence of baseline undernutrition in patients of ALL was 66%. In one study by Radhakrishnan et al.,[13] 44% of pediatric cancer patients were undernourished at diagnosis.

A study carried out by Tazi et al.[14] in Morocco, the prevalence of malnutrition at diagnosis in children with cancer was found to be high. It ranged from 20% to 50%, according to the measurements used. This study reflects conditions common to developing countries.

In the present study, ALL patients with acute undernutrition had higher risk of severe infection during induction phase chemotherapy, but the variation was not statistically significant. This study has limitation of small sample size. Only those patients who survived induction were included in our study. In a study similar to ours by Kumar et al.,[10] malnourished children had more risk of infection compared to well nourished. This variation was of borderline statistical significance.

In ALL, previous studies suggests that protein-energy undernutrition at diagnosis is an adverse prognostic factor.[15],[16],[17] Similarly in a previous study by Jain et al.,[11] malnourished children by weight-for-height criteria were observed to have statistically significant lower rates of achievement of remission, poor response to therapy and a greater incidence of delay in treatment. However, study by Tandon et al.[12] did not find any significant correlation between nutritional status and survival of patients. In our study, the mortality percentage in the patients with baseline acute undernutrition was higher though the difference was not statistically significant. The deaths were in different phases of chemotherapy after induction of remission phase.

In our study, male gender and hypoalbuminemia were significantly associated with severe infection in acute undernutrition group. In a previous study[11] on childhood cancer patients, the mean values of total proteins and serum albumin were significantly higher for survivors when compared with non-survivors.

Our study signifies the burden of undernutrition as well as the importance of nutritional status in patients with ALL. Now we take nutritional concern with more serious note and give advices on diet and hygiene on regular basis to the ALL patients and relatives.


  Conclusion Top


The burden of acute undernutrition in children with ALL is very high in our center. There is increased risk of infection during induction phase chemotherapy in ALL patients with acute undernutrition compared to those without acute undernutrition but the difference was not found to be significant statistically. The mortality after induction phase chemotherapy in patients with baseline acute undernutrition was also higher than normal nutrition patients. But the difference is not statistically significant. Our study highlights the importance of nutritional intervention to improve outcome in patients with ALL.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
National Family Health Survey 4, India Fact Sheet 2015-16, International Institute for Population Sciences, Mumbai. Available from: http://rchiips.org/nfhs/pdf/NFHS4/India.pdf. [Last accessed on 2019 Jan 19].  Back to cited text no. 1
    
2.
Metzger ML, Howard SC, Fu LC, Peña A, Stefan R, Hancock ML, et al. Outcome of childhood acute lymphoblastic leukaemia in resource-poor countries. Lancet 2003;362:706-8.  Back to cited text no. 2
    
3.
Tisdale MJ. Cancer cachexia: Metabolic alterations and clinical manifestations. Nutrition 1997;13:1-17.  Back to cited text no. 3
    
4.
Bauer J, Jürgens H, Frühwald MC. Important aspects of nutrition in children with cancer. Adv Nutr 2011;2:67-77.  Back to cited text no. 4
    
5.
Reilly JJ, Weir J, McColl JH, Gibson BE. Prevalence of protein-energy malnutrition at diagnosis in children with acute lymphoblastic leukemia. J Pediatr Gastroenterol Nutr 1999;29:194-7.  Back to cited text no. 5
    
6.
Uderzo C, Rovelli A, Bonomi M, Barzaghi A, Strada S, Balduzzi A, et al. Nutritional status in untreated children with acute leukemia as compared with children without malignancy. J Pediatr Gastroenterol Nutr 1996;23:34-7.  Back to cited text no. 6
    
7.
Roy A, Saha A, Chakraborty S, Chattopadhyay S, Sur PK. Effects of pre-existing undernutrition on treatmentrelated complications and treatment outcomes in children with acute lymphoblastic leukemia: A tertiary care center experience. Clin Cancer Investig J 2013;2:143-8.  Back to cited text no. 7
  [Full text]  
8.
Linga VG, Shreedhara AK, Rau AT, Rau A. Nutritional assessment of children with hematological malignancies and their subsequent tolerance to chemotherapy. Ochsner J 2012;12:197-201.  Back to cited text no. 8
    
9.
Sharma R. Revised Kuppuswamy's socioeconomic status scale: Explained and updated. Indian Pediatr 2017;54:867-70.  Back to cited text no. 9
    
10.
Kumar R, Marwaha RK, Bhalla AK, Gulati M. Protein energy malnutrition and skeletal muscle wasting in childhood Acute Lymphoblastic Leukemia. Indian Pediatr 2000;37:720-6.  Back to cited text no. 10
    
11.
Jain V, Dubey AP, Gupta SK. Nutritional parameters in children with malignancy. Indian Pediatr 2003;40:976-84.  Back to cited text no. 11
    
12.
Tandon S, Moulik NR, Kumar A, Mahdi AA, Kumar A. Effect of pre-treatment nutritional status, folate and vitamin B12 levels on induction chemotherapy in children with acute lymphoblastic leukemia. Indian Pediatr 2015;52:385-9.  Back to cited text no. 12
    
13.
Radhakrishnan V, Ganesan P, Rajendranath R, Ganesan TS, Sagar TG. Nutritional profile of pediatric cancer patients at Cancer Institute, Chennai. Indian J Cancer 2015;52:207-9.  Back to cited text no. 13
[PUBMED]  [Full text]  
14.
Tazi I, Hidane Z, Zafad S, Harif M, Benchekroun S, Ribeiro R. Nutritional status at diagnosis of children with malignancies in casablanca. Pediatr Blood Cancer 2008;51:495-8.  Back to cited text no. 14
    
15.
Reilly JJ, Odame I, McColl J, McAllister PJ, Gibson BE, Wharton BA. Does weight for height have prognostic significance in children with ALL? Am J Pediatr Hematol Oncol 1994;16:225-30.  Back to cited text no. 15
    
16.
Borato-Viana M, Murao M, Ramos G, Oliveira HM, de Carvalho RI, de Bastos M, et al. Malnutrition as a prognostic factor in lymphoblastic leukaemia: A multivariate analysis. Arch Dis Child 1994;71:304-10.  Back to cited text no. 16
    
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Lobato-Mendizabal E, Ruiz-Arguelles GJ, Marin-Lopez A. Leukaemia and nutrition I. LeukRes 1989;13:899-906.  Back to cited text no. 17
    



 
 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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