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Impact of Sociodemographic Factors and Nutrition on the Duration of Induction Phase of Chemotherapy in children with Acute lymphoblastic leukemia: A Tertiary Center Experience from North India
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2020; 41(03): 368-371
DOI: DOI: 10.4103/ijmpo.ijmpo_226_18
Abstract
Background: Immunocompromised patients are at increased risk of infections, especially those living in poor hygienic conditions. Aims and Objectives: This study aims to assess the effect of weight, immunization status of the child at the start of treatment along with the socioeconomic status (SES), and demographic parameters, i.e., type of house, sanitary facility (SF), and source of drinking water on the duration of induction phase of chemotherapy (delayed if the patient received chemotherapy for >29 days). Materials and Methods: 110 pediatric acute lymphoblastic leukemia patients aged 1.5–14 years who underwent induction of remission from June 2015 to February 2018 were included. The immunization status and weight of the child were recorded at the start of treatment. SES was assessed using modified Kuppuswami scale and a questionnaire was used to determine various sociodemographic parameters. Results: The patients not immunized as per age (P = 0.000) and having poor demographic parameters, i.e., mud house (P = 0.000), absence of SF (P = 0.013), and nonfiltered drinking water (P = 0.005), had significant delay. The duration of induction phase of chemotherapy was not delayed with poor SES (P = 0.832). Although the duration was delayed in patients with weight ≥10 percentile, it was not statistically significant (P = 0.079). On analyzing the three demographic parameters together as Water-Sanitary Facility-Housing (WaSH) Score (0–4), the duration was also significantly delayed if the patients had WaSH score < 2. Conclusion: The duration of induction phase of chemotherapy is delayed with inadequate immunization status and poor hygiene of the child.
Publication History
Received: 16 October 2018
Accepted: 17 September 2019
Article published online:
28 June 2021
© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
Abstract
Background: Immunocompromised patients are at increased risk of infections, especially those living in poor hygienic conditions. Aims and Objectives: This study aims to assess the effect of weight, immunization status of the child at the start of treatment along with the socioeconomic status (SES), and demographic parameters, i.e., type of house, sanitary facility (SF), and source of drinking water on the duration of induction phase of chemotherapy (delayed if the patient received chemotherapy for >29 days). Materials and Methods: 110 pediatric acute lymphoblastic leukemia patients aged 1.5–14 years who underwent induction of remission from June 2015 to February 2018 were included. The immunization status and weight of the child were recorded at the start of treatment. SES was assessed using modified Kuppuswami scale and a questionnaire was used to determine various sociodemographic parameters. Results: The patients not immunized as per age (P = 0.000) and having poor demographic parameters, i.e., mud house (P = 0.000), absence of SF (P = 0.013), and nonfiltered drinking water (P = 0.005), had significant delay. The duration of induction phase of chemotherapy was not delayed with poor SES (P = 0.832). Although the duration was delayed in patients with weight ≥10 percentile, it was not statistically significant (P = 0.079). On analyzing the three demographic parameters together as Water-Sanitary Facility-Housing (WaSH) Score (0–4), the duration was also significantly delayed if the patients had WaSH score < 2. Conclusion: The duration of induction phase of chemotherapy is delayed with inadequate immunization status and poor hygiene of the child.
Keywords
Induction - leukemia - pediatric - socioeconomic factorsIntroduction
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy worldwide, accounting for about 30% of all childhood malignancies.[1] According to the GLOBOCAN 2012 estimates (http://globocan.iarc.fr/), nearly 25,000 children in India are diagnosed with cancer each year, among which approximately 9000 children are diagnosed with acute leukemia. Although worldwide estimates for overall 5-year survival rate in ALL patients are more than 85%, exact data for the Indian population are lacking in the present literature.[1],[2] A population-based cancer registry from Chennai and Bengaluru suggests a much lower cure rate in India.
According to the WHO/United Nations Children's Fund (2015), approximately 2.9 billion people worldwide have access to improved sanitary facilities or measures to sequester human feces from the environment including pit latrines with slabs. A majority of population, i.e., around 892 million, worldwide do not have access to sanitary facilities whatsoever and practice open field defecation, rampant in rural and urban slums in South and Southeast Asia as well as Sub-Saharan Africa. India is the largest contributor of open field defecation in the world, practiced by nearly 600 million people. 844 million people worldwide lack a basic drinking water service. In India, 1.2 billion people have access to drinking water from improved sources.[3]
Various factors are responsible for lower overall as well as event-free survival rate in children with ALL in India such as delay in diagnosis, malnutrition, infections, abandonment, limited resources, as well as limited access to adequate treatment. One of the major causes of recurrent infections in Indian children is poor living conditions. Although patients have access to sanitary latrines and filtered drinking water in the hospital, they lack the same at home. Furthermore, few of the patients after being discharged from hospital live in an overcrowded house made of mud, which results in a cycle of infection, hospitalization, and undernutrition. This results in prolonged hospitalization as well as delay in completion of treatment.
Previous studies have analyzed the effect of socioeconomic status (SES) of the child, parental education, and time to reach hospital for chemotherapy on the event-free as well as overall survival.[4],[5],[6] In our study, we tried to systematically evaluate the effect of sociodemographic parameters on the duration of induction phase of chemotherapy.
Materials and Methods
After an ethical clearance from the institutional ethics committee, children with ALL who underwent induction of remission from June 2015 to February 2018 were included in the study.
A questionnaire was used to record the weight and immunization status of the child and assess the type of house, source of drinking water, and sanitary facilities before start of treatment. The following definitions were used in the questionnaire:
Type of house: (i) Brick house: House where the floor is paved, walls are stone or brick-built, and roof is made of asbestos or concrete. (ii) Mud House: House in which floor is packed earth, walls are made of dried mud or thatched, and roof is thatched or comprises slate
Source of drinking water: (i) Filtered water: Drinking water obtained from reverse osmosis purifier system installed in the household or bottled water. (ii) Nonfiltered water: Drinking water obtained from hand pump, tap, submersible pump, and well
Sanitary facility (SF): (i) SF present: The presence of pit latrine with/without pour-flush system. (ii) SF absent: Open field defecation.
Our patients received modified children's oncology group protocol. Children were stratified into standard risk and high risk based on the National Cancer Institute/Rome criteria, which include (i) age, (ii) total leukocyte count (TLC), (iii) immunophenotype, (iv) cytogenetics, and (v) central nervous system (CNS) status. Children in the standard risk group (age, 1–9 years, TLC, < 50,000/mm3, pre-B cell ALL, favorable cytogenetics, i.e., t (12;21), hyperdiploidy, and CNS status I) received 3-drug induction with vincristine, L-asparaginase, and intrathecal methotrexate and those in the high-risk group (age >9 years, TLC, ≥50,000/mm3, T-cell ALL, unfavorable cytogenetics, i.e., t (9;22), t (1;19), mixed lineage leukemia rearrangement, hypodiploidy, and CNS status II/III) received 4-drug induction with vincristine, L-asparaginase, daunorubicin, and intrathecal methotrexate. For the induction phase of chemotherapy, patients were admitted in the hospital for 10–14 days depending on their counts and clinical status, following which they were discharged to attend our day care chemotherapy clinic for further injections. Usually, it took 29 days to achieve the end of induction phase of chemotherapy. Only those patients who did not experience febrile illness during hospital stay and were stable at the time of discharge were included. We hypothesized that the adverse sociodemographic parameters result in episodes of infection causing reduction in counts and delay in completion of induction chemotherapy. The duration of induction phase of chemotherapy was considered delayed, if the patient received chemotherapy for more than 29 days. Those who died during induction or abandoned the treatment were excluded from the study.
The immunization status of the patients was assessed keeping in view of the National Immunization Schedule of India, which includes timely doses of bacillus Calmette–Guérin, hepatitis B, diphtheria–pertussis–tetanus, and measles. The patients who received the vaccines were considered immunized as per age.
Weight for age percentile of the child was determined using the WHO growth charts to divide the patients into two groups, i.e., weight for age < 10 percentile and weight for age ≥10 percentile. The SES of patients was assessed using Kuppuswamy Scale which includes education of the father, his occupation, and monthly income.
Apart from evaluating these parameters individually, a water-SF-housing (WaSH) score was further devised and analyzed to predict the delay in the duration of induction phase of chemotherapy. The WaSH score consisted of (i) source of drinking water (filtered water = 1 and nonfiltered water = 0), (ii) SF (present = 1 and absent = 0), and (iii) the type of house (mud house = 0 and brick house = 1), with a maximum score of 3 and a minimum score of 0.
Statistical methods
Data management and statistical analysis was performed using SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). The data were presented as mean ± standard deviation for continuous variables and as frequency and percentage for categorical variables. Independent sample t-test was used to compare two groups with respect to normally distributed numerical data. P < 0>
Results
One hundred and ten children of pediatric ALL with a mean age 6.5 ± 3.5 years were enrolled with a male-to-female ratio of 2.6:1. Demographic characteristics of the sample population among the two groups are provided in [Table 1]. The duration of induction chemotherapy was delayed in 71 children with a total duration of ≤36 days in 47 children, managed on an outpatient basis for an episode of mild febrile neutropenia, and >36 days in 24 children, admitted in hospital for severe febrile neutropenia. Among the children who were admitted for febrile neutropenia, 33% had acute gastroenteritis, 32% had lower respiratory tract infection, 29% had skin and soft-tissue infections, and 6% had urinary tract infection. The most common organism isolated was Staphylococcus aureus (46%), followed by Gram-negative organisms (39%), i.e., Klebsiella pneumoniae, Escherichiacoli, and Pseudomonas. Fungal sepsis contributed 15% among the isolated organisms. The patients with respiratory infections had more delay as compared to infection at other sites.
Drugs used in various treatment protocols used to treat acute lymphoblastic leukemia
|
Characteristics |
Results |
|||||
|---|---|---|---|---|---|---|
|
SD – Standard deviation; SES – Socioeconomic status; SF – Sanitary facility |
||||||
|
Age (years), mean±SD |
6.5±3.5 |
|||||
|
Male:female |
2.6:1 |
|||||
|
Nutrition, n (%) |
||||||
|
Normal nutrition |
89 (80.9) |
|||||
|
Under nutrition |
21 (19.1) |
|||||
|
SF, n (%) |
||||||
|
Yes |
64 (58.2) |
|||||
|
No |
46 (41.8) |
|||||
|
SES, n (%) |
||||||
|
≤III |
60 (55.5) |
|||||
|
≥IV |
50 (45.5) |
|||||
|
Water supply, n (%) |
||||||
|
Filtered |
35 (31.8) |
|||||
|
Nonfiltered |
75 (68.2) |
|||||
|
Type of house, n (%) |
||||||
|
Brick house |
70 (63.6) |
|||||
|
Mud house |
40 (36.4) |
|||||
|
Immunization status, n (%) |
||||||
|
Yes |
76 (69.1) |
|||||
|
No |
34 (30.9) |
|||||
Effect of various parameters on the duration of induction phase of chemotherapy
|
Duration of induction |
P |
|
|---|---|---|
|
SES – Socioeconomic status |
||
|
SES |
||
|
Lower (n=50) |
33.32±5.7 |
0.832 |
|
Middle (n=60) |
33.42±6.72 |
|
|
House |
||
|
Mud house (n=40) |
37.58±7.78 |
0.000 |
|
Brick house (n=70) |
30.97±3.439 |
|
|
Sanitary latrine |
||
|
Absent (n=46) |
35.11±7.87 |
0.013 |
|
Present (n=64) |
32.13±4.47 |
|
|
Water supply |
||
|
Nonfiltered water (n=75) |
34.5±6.89 |
0.005 |
|
Filtered water (n=35) |
30.94±3.74 |
|
|
Immunization status |
||
|
No (n=34) |
38.85±7.782 |
0.000 |
|
Yes (n=76) |
30.92±3.298 |
|
|
Weight |
||
|
less than 10 percentile (n=58) |
32.38±5.57 |
0.079 |
|
≥10 percentile (n=52) |
34.48±6.86 |
|
A WaSH score of 0 or 1 was significantly associated with delay in duration of induction phase of chemotherapy (P = 0.000) [Table 3].
Table 3Water, sanitation, house score
|
Score |
Duration of induction(days) |
P |
|---|---|---|
|
less than 2 (n=50) |
35.98±7.71 |
0.000 |
|
≥2 (n=60) |
31.20±3.56 |
Survival rates are poor in developing countries due to high treatment-related mortality (TRM) attributed partly to high prevalence of malnutrition[7] and infection. Infection is the most common cause of TRM even in developed countries. The incidence of TRM on contemporary trials in ALL is 2%–4%.[8],[9] It has been postulated that malnutrition results in immune dysfunction causing poor tolerance to infections and altered drug metabolism leading to higher drug toxicity and adverse clinical outcomes.[9],[10]
Several studies in developed countries have evaluated the effect of undernutrition on prognosis and survival of patients with acute leukemia. Interestingly, both undernutrition and obesity are associated with an inferior event free-survival as reported by Orgel et al.[11] A study from India by Roy et al. stated that undernourished children experience more episodes of febrile neutropenia resulting in poor outcome.[12],[13] Thus, nutritional status of the child at the start of treatment correlates with outcome. In our study, however, the duration of induction was not significantly affected by the nutritional status of the child (P = 0.079).
Apart from nutritional status, our study also focused on the influence of immunization status of the child and SES along with associated demographic factors on the duration of induction phase of chemotherapy. Many studies have assessed the effect of SES on the incidence of ALL as well as its effect on overall survival and relapse, with only few studies from developing countries including India.[14],[15],[16]
In our study, children with poor living conditions, i.e., children residing in a mud house with no access to SF and filtered drinking water, had a delay in the duration of induction phase of chemotherapy. Furthermore, the delay in induction was experienced by those who were not immunized before start of induction chemotherapy (P < 0>
Conclusion
Disease as well as chemotherapy weakens the immune system, predisposing patients with cancer to innumerable infections resulting in multiple hospitalizations, increasing the incidence of relapses as well as patient succumbing to fatal infections. It is already known that the delay in early phase of chemotherapy can affect overall survival. Thus, to curb delay in chemotherapy due to infectious causes and thereby improve outcome, an improvement in living conditions can play an important role. This study subjectively evaluates the living condition of patients and its effect on the duration of chemotherapy.
The authors of this study feel that interruptions during induction chemotherapy due to infections results in dose reduction/stoppage of chemotherapeutic agents during the febrile episode, causing delay in completion of induction chemotherapy. This may have an adverse effect on overall and event-free survival of patients with acute leukemia. More studies are needed to support the effect of interruption during induction chemotherapy on overall/event-free survival in patients with acute leukemia.
Conflict of Interest
There are no conflicts of interest.
References
- National Cancer Institute. SEER Cancer Statistics Review. Bethesda, MD: National Cancer Institute. Available from: http:// seer.cancer.gov/faststats/selections.php?#Output. [Last accessed on 2016 Apr 04]
- Gatta G, Capocaccia R, Stiller C, Kaatsch P, Berrino F, Terenziani M. et al. Childhood cancer survival trends in Europe: A EUROCARE working group study. J Clin Oncol 2005; 23: 3742-51
- World Health Organization and the United Nations Children's Fund. Progress on Drinking Water, Sanitation and Hygiene: 2017 Update and SDG Baselines.Geneva: World Health Organization and the United Nations Children's Fund; 2017
- Coebergh JW, van der Does-van den BergA, Hop WC, van WeerdenF, Rammeloo JA, van Steensel HA. et al Small in uence of parental educational level on the survival of children with leukaemia in the Netherlands between 1973 and 1979. Eur J Cancer 1996; 32A: 286-9
- Syse A, Lyngstad TH, Kravdal O. Is mortality after childhood cancer dependent on social or economic resources of parents? A population-based study. Int J Cancer 2012; 130: 1870-8
- Totadri S, Trehan A, Kaur A, Bansal D, Jain R. Does distance between residence and treating center impact outcome in childhood acute lymphoblastic leukemia? Report from a tertiary care center in North India. Pediatr Hematol Oncol J 2016; 1: S1-33
- Advani S, Pai S, Venzon D, Adde M, Kurkure PK, Nair CN. et al. Acute lymphoblastic leukemia in India: An analysis of prognostic factors using a single treatment regimen. Ann Oncol 1999; 10: 167-76
- Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ. et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: A report from the children's oncology group. J Clin Oncol 2012; 30: 1663-9
- Bauer J, Jürgens H, Frühwald MC. Important aspects of nutrition in children with cancer. Adv Nutr 2011; 2: 67-77
- Tisdale MJ. Cancer cachexia: Metabolic alterations and clinical manifestations. Nutrition 1997; 13: 1-7
- Orgel E, Sposto R, Malvar J, Seibel NL, Ladas E, Gaynon PS. et al. Impact on survival and toxicity by duration of weight extremes during treatment for pediatric acute lymphoblastic leukemia: A report from the children's oncology group. J Clin Oncol 2014; 32: 1331-7
- Roy A, Saha A, Chakraborty S, Chattopadhyay S, Sur PK. Effects of pre-existing undernutrition on treatment related complications and treatment outcomes in children with acute lymphoblastic leukemia: A tertiary care centre experience. Clin Cancer Invest J 2013; 2: 143-8
- 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
- Bona K, Blonquist TM, Neuberg DS, Silverman LB, Wolfe J. Impact of socioeconomic status on timing of relapse and overall survival for children treated on Dana-Farber cancer institute ALL consortium protocols (2000-2010). Pediatr Blood Cancer 2016; 63: 1012-8
- Gupta S, Wilejto M, Pole JD, Guttmann A, Sung L. Low socioeconomic status is associated with worse survival in children with cancer: A systematic review. PLoS One 2014; 9: e89482
- Totadri S, Trehan A, Kaur A, Bansal D, Jain R. Socio-economic status and survival in children with acute lymphoblastic leukemia. Pediatr Hematol Oncol J 2016; 1: S1-33
Address for correspondence
Publication History
Received: 16 October 2018
Accepted: 17 September 2019
Article published online:
28 June 2021
© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
References
- National Cancer Institute. SEER Cancer Statistics Review. Bethesda, MD: National Cancer Institute. Available from: http:// seer.cancer.gov/faststats/selections.php?#Output. [Last accessed on 2016 Apr 04]
- Gatta G, Capocaccia R, Stiller C, Kaatsch P, Berrino F, Terenziani M. et al. Childhood cancer survival trends in Europe: A EUROCARE working group study. J Clin Oncol 2005; 23: 3742-51
- World Health Organization and the United Nations Children's Fund. Progress on Drinking Water, Sanitation and Hygiene: 2017 Update and SDG Baselines.Geneva: World Health Organization and the United Nations Children's Fund; 2017
- Coebergh JW, van der Does-van den BergA, Hop WC, van WeerdenF, Rammeloo JA, van Steensel HA. et al Small in uence of parental educational level on the survival of children with leukaemia in the Netherlands between 1973 and 1979. Eur J Cancer 1996; 32A: 286-9
- Syse A, Lyngstad TH, Kravdal O. Is mortality after childhood cancer dependent on social or economic resources of parents? A population-based study. Int J Cancer 2012; 130: 1870-8
- Totadri S, Trehan A, Kaur A, Bansal D, Jain R. Does distance between residence and treating center impact outcome in childhood acute lymphoblastic leukemia? Report from a tertiary care center in North India. Pediatr Hematol Oncol J 2016; 1: S1-33
- Advani S, Pai S, Venzon D, Adde M, Kurkure PK, Nair CN. et al. Acute lymphoblastic leukemia in India: An analysis of prognostic factors using a single treatment regimen. Ann Oncol 1999; 10: 167-76
- Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ. et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: A report from the children's oncology group. J Clin Oncol 2012; 30: 1663-9
- Bauer J, Jürgens H, Frühwald MC. Important aspects of nutrition in children with cancer. Adv Nutr 2011; 2: 67-77
- Tisdale MJ. Cancer cachexia: Metabolic alterations and clinical manifestations. Nutrition 1997; 13: 1-7
- Orgel E, Sposto R, Malvar J, Seibel NL, Ladas E, Gaynon PS. et al. Impact on survival and toxicity by duration of weight extremes during treatment for pediatric acute lymphoblastic leukemia: A report from the children's oncology group. J Clin Oncol 2014; 32: 1331-7
- Roy A, Saha A, Chakraborty S, Chattopadhyay S, Sur PK. Effects of pre-existing undernutrition on treatment related complications and treatment outcomes in children with acute lymphoblastic leukemia: A tertiary care centre experience. Clin Cancer Invest J 2013; 2: 143-8
- 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
- Bona K, Blonquist TM, Neuberg DS, Silverman LB, Wolfe J. Impact of socioeconomic status on timing of relapse and overall survival for children treated on Dana-Farber cancer institute ALL consortium protocols (2000-2010). Pediatr Blood Cancer 2016; 63: 1012-8
- Gupta S, Wilejto M, Pole JD, Guttmann A, Sung L. Low socioeconomic status is associated with worse survival in children with cancer: A systematic review. PLoS One 2014; 9: e89482
- Totadri S, Trehan A, Kaur A, Bansal D, Jain R. Socio-economic status and survival in children with acute lymphoblastic leukemia. Pediatr Hematol Oncol J 2016; 1: S1-33