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Assessment of Baseline Nutritional Status, Vitamin B12, and Folate Levels in Patients with Acute Leukemia and Their Effect on Initial Treatment Outcome: A Prospective Observational Study
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2022; 43(02): 171-176
DOI: DOI: 10.1055/s-0042-1742665
Abstract
Introduction Poor nutrition is a common finding in patients with acute leukemia, affecting disease progression, treatment outcome, and survival. Overall nutritional status and micronutrients status evaluation may be an important step in management of acute leukemia.
Objective The objective of this study was to investigate baseline nutritional status, vitamin B12, and folate levels in patients with acute leukemia at the time of admission before starting chemotherapy and their initial treatment outcome.
Materials and Methods This was a prospective observational study. We assessed the pretreatment nutritional status of 73 patients by body mass index (BMI), serum vitamin B12 using a two-step chemiluminescent microparticle immunoassay, and serum folate using electrochemiluminescence by Cobas e411 analyzer before initiation of induction chemotherapy and evaluated for treatment response at the end of induction chemotherapy.
Results Out of a total of 73 patients, 51 (69.8%) completed induction chemotherapy, 36 (49.3%) showed complete remission, and 15 (20.5%) were in incomplete remission. Of the remaining 22 (30.1%) patients, 11 (15.1%) died due to toxicity during therapy. The mean values of baseline BMI, serum vitamin B12, and folate was 20.46 kg/m2, 956.04, and 13.52 ng/mL, respectively. There was no significant association between vitamin B12 (p-value = 0.609) and folate (p-value = 0.404) deficiency and the response to treatment.
Conclusion Baseline nutritional status, serum vitamin B12, and folate levels have no significant role in induction outcome in response to treatment, including mortality in patients with acute leukemia.
Note
The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and each author believes that the manuscript represents honest work.
Financial Support and Sponsorship
Nil.
Publication History
Article published online:
14 March 2022
© 2022. 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/)
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Abstract
Introduction Poor nutrition is a common finding in patients with acute leukemia, affecting disease progression, treatment outcome, and survival. Overall nutritional status and micronutrients status evaluation may be an important step in management of acute leukemia.
Objective The objective of this study was to investigate baseline nutritional status, vitamin B12, and folate levels in patients with acute leukemia at the time of admission before starting chemotherapy and their initial treatment outcome.
Materials and Methods This was a prospective observational study. We assessed the pretreatment nutritional status of 73 patients by body mass index (BMI), serum vitamin B12 using a two-step chemiluminescent microparticle immunoassay, and serum folate using electrochemiluminescence by Cobas e411 analyzer before initiation of induction chemotherapy and evaluated for treatment response at the end of induction chemotherapy.
Results Out of a total of 73 patients, 51 (69.8%) completed induction chemotherapy, 36 (49.3%) showed complete remission, and 15 (20.5%) were in incomplete remission. Of the remaining 22 (30.1%) patients, 11 (15.1%) died due to toxicity during therapy. The mean values of baseline BMI, serum vitamin B12, and folate was 20.46 kg/m2, 956.04, and 13.52 ng/mL, respectively. There was no significant association between vitamin B12 (p-value = 0.609) and folate (p-value = 0.404) deficiency and the response to treatment.
Conclusion Baseline nutritional status, serum vitamin B12, and folate levels have no significant role in induction outcome in response to treatment, including mortality in patients with acute leukemia.
Introduction
Poor nutrition is a common finding in patients with hematological malignancy, affecting disease progression and survival.[1] Human beings require macronutrients (carbohydrates, fats, and proteins) and micronutrients (vitamins, minerals, and other biochemicals) for nearly all metabolic and developmental processes. Micronutrients are critical for several vital functions in our body. Their deficiency is a significant health problem in India.[2] Data on micronutrient status in people are not available; however, recent studies from India have highlighted that people suffer from micronutrient deficiency.[3] Earlier reported data indicate that 47%- of the north Indian population had a deficit of vitamin B12.[4] This may be due to multiple reasons: a significant proportion of the Indian population, 29%-is vegetarian,[5] and other factors such as poor nutrition, malabsorption, and other gastrointestinal causes may also be responsible.[6] [7] The elderly and alcoholics are prone to vitamin B12 due to poor oral intake.[8] [9] Various studies suggest that vitamin B12 deficiency is more common in hematological malignancies than nonhematological diseases.[10] [11] Earlier studies indicate that folate deficiency exists in 40%-of the Indian population.[12] [13] [14] Inadequate serum folate levels may increase cancer risk, including hematological malignancies.[15] [16] [17]
Vitamin B12 and folate act as coenzymes that participate in one-carbon metabolism involved in DNA methylation and DNA synthesis.[18] [19] Inadequate intake of these micronutrients may disrupt one-carbon metabolism resulting in the risk of developing hematological malignancies.[16] Hence, the need of the hour is to evaluate the baseline status of vitamin B12 and folate in patients with hematological malignancies.
Very few studies have been performed for determining the micronutrient status (vitamin B12 and folate) in acute leukemia, and mostly, these have been done in the pediatric population.[20] [21] [22] It is essential to know the levels of nutritional status and their impact on the treatment and quality of life. Therefore, in this study, we aimed to investigate baseline nutritional status, serum vitamin B12 levels, and folate levels in patients with acute leukemia and evaluate their effect on response to therapy.
Materials and Methods
Study Participants
This study included patients with newly diagnosed acute leukemia presenting to the clinical haematology department of a tertiary care teaching and referral institute in northern India, from September 2018 to September 2019.
Inclusion and Exclusion Criteria
Patients suffering from acute leukemia and age older than 13 years, attending the department of clinical hematology OPD were consecutively included in this study. Prior to enrollment of the patient, written informed consent was obtained from him/her or legally authorized relative.
Patients who were unwilling to give written informed consent, those who were already on chemotherapy and using drugs containing vitamin B12 and folate, and those who had undergone gastric or ileocecal resection (which could potentially interfere with the absorption of vitamin B12) were excluded from the study.
Outcome Measures
Primary outcome measure was to study the association of nutritional status, vitamin B12, and folate levels with induction remission status of acute leukemia patients. Secondary outcome measure was to study the association of nutritional status, vitamin B12, and folate levels with induction-related death.
Data Collection
We collected baseline nutritional data of patients at the time of their admission in the ward before starting chemotherapy. Measurement of height (in cm), weight (in kg), body mass index (BMI), socioeconomic condition,[23] physical activity level,[24] food habits, serum protein, and serum albumin were recorded. Calculation of calorie and protein intake was done. Weight was measured in kilogram using a weighing scale, and height was measured in centimeter by using a stadiometer. Data on weight and height were collected to the nearest 0.1 kg and 1 cm, respectively. BMI was calculated using the formula: person's weight in kilogram divided by his/her height in meter squared. BMI is a calculated number that represents a person's level of fat or obesity level. BMI level was classified as: underweight (BMI <18>30).[25]
To calculate calorie and protein, dietary guidelines of National Institute of Nutrition (NIN) Hyderabad, India was followed. Patients' 24-hour dietary recall was maintained according to feedback given by their attendant. The food exchange method (NIN) was used for the calculation of nutrients. The food frequency table was also recorded at the time of admission to get detailed information about patients' food habits, likes, and dislikes.
Complete hemogram (hemoglobin, total leukocyte count, differential leukocyte count, platelets, total red blood cells), liver function test (serum bilirubin, SGOT, SGPT, serum alkaline phosphatase), kidney function test (serum urea, serum creatinine, uric acid), serum electrolyte, serum calcium, serum magnesium, and serum phosphorus were done; enzyme-linked immunosorbent assay was used to test viral markers including hepatitis B surface antigen, hepatitis C virus, and human immunodeficiency virus.
Criteria for a complete remission of acute leukemia was bone marrow aspiration and biopsy <5>
Sample Collection for Micronutrients
For estimation of micronutrients, a 2-mL blood sample was collected in plain vials from individuals. Serum levels of vitamin B12 were determined by using a two-step chemiluminescent microparticle immunoassay, and levels were expressed in picogram/milliliter (pg/mL). The serum level of folate was measured by using Cobas e411 analyzer, and levels were expressed in nanogram/milliliter (ng/mL). The cutoff value for serum vitamin B12 was < 203 pg/mL, while it was <4 ng/mL for folate to determine the deficiency levels.[26]
Statistical Analysis
The data were entered in MS Excel spreadsheet, and analysis was done using Statistical Package for Social Sciences (SPSS) version 16.0 (SPSS Inc., Chicago, Illinois, United States). Categorical variables were presented in numbers, and percentages (%) and continuous variables were presented as mean ± standard deviation (SD). Qualitative variables were compared using the chi-square test. A p-value of <0>
Ethics
The procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Declaration of Helsinki 1964, as revised in 2013. Ethics committee approval was obtained from the King George's Medical University institutional ethics committee dated August 28, 2018, number 91st ECM II A/P5 prior to enrollment of the patient, and written informed consent was obtained from him/her or legally authorized relative.
Results
Patient Characteristics
Seventy-three newly diagnosed patients enrolled between September 2018 and September 2019 were included in the study. There were 44 (60.3%) males and 29 (39.7%) females with an M:F ratio of 1.5:1. All the patients belonged to either lower, 47 (64.4%), or middle socioeconomic strata, 26 (35.6%). The mean (SD) age of patients was 30.32 (14.95) years ([Table 1]). The average mean (SD) of anthropometric variables such as weight, height, and BMI of these patients was 52.29 (11.07) kg, 180.12 (166.30) cm, and 20.46 (3.96) kg/m2, respectively. [Table 1] depicts the general baseline characteristics of the patients.
|
Characteristic |
Categories |
Number (73) |
Percentage |
|---|---|---|---|
|
Age (y) |
Mean ± SD |
30.32 (14.95) |
|
|
Range |
13–70 |
||
|
Sex |
Male |
44 |
60.3 |
|
Female |
29 |
39.7 |
|
|
Socioeconomic condition |
Low |
47 |
64.4 |
|
Middle |
26 |
35.6 |
|
|
Physical activity level |
Active |
11 |
15.1 |
|
Low |
28 |
38.4 |
|
|
Moderate |
34 |
46.6 |
|
|
Dietary habit |
Nonvegetarian |
44 |
60.3 |
|
Vegetarian |
29 |
39.7 |
|
|
Addiction |
No addiction |
49 |
67.1 |
|
Smoking |
5 |
6.8 |
|
|
Alcohol |
2 |
2.7 |
|
|
Tobacco |
17 |
23.3 |
|
|
Nutritional status |
|||
|
BMI |
Normal |
43 |
58.9 |
|
Obese |
2 |
2.7 |
|
|
Overweight |
6 |
8.2 |
|
|
Underweight |
22 |
30.1 |
|
|
Calorie (kcal) |
Mean ± SD |
1127.49 (414.50) |
|
|
Protein (g) |
Mean ± SD |
24.82 (10.02) |
|
|
Serum protein (g/dL) |
Mean ± SD |
6.53 (1.12) |
|
|
Range |
3.83–8.62 |
||
|
Serum albumin (g/dL) |
Mean ± SD |
3.65 (0.63) |
|
|
Range |
1.80–4.80 |
||
|
Vitamin B12 (pg/mL) |
Mean ± SD |
956.04 (1,178.41) |
|
|
Range |
83–5,960 |
||
|
Folate (ng/mL) |
Mean ± SD |
13.52 (9.63) |
|
|
Range |
2.2–41.2 |
||
|
Response |
p-Value |
|||||||
|---|---|---|---|---|---|---|---|---|
|
Complete remission |
Incomplete remission |
Death due to toxicity |
||||||
|
N |
% |
N |
% |
N |
% |
|||
|
Vitamin B12 |
≤203 |
12 |
33.3% |
4 |
26.7% |
2 |
18.2% |
0.609 |
|
>203 |
24 |
66.7% |
11 |
73.3% |
9 |
81.8% |
||
|
Folate |
≤4 |
2 |
5.6% |
1 |
7.1% |
2 |
18.2% |
0.404 |
|
>4 |
34 |
94.4% |
13 |
92.9% |
9 |
81.8% |
||
|
Total protein |
<6> |
10 |
27.8% |
3 |
20.0% |
2 |
18.2% |
0.736 |
|
≥6 |
26 |
72.2% |
12 |
80.0% |
9 |
81.8% |
||
|
Albumin |
<3> |
12 |
33.3% |
4 |
26.7% |
6 |
54.5% |
0.312 |
|
≥3.5 |
24 |
66.7% |
11 |
73.3% |
5 |
45.5% |
||
|
BMI |
<18> |
7 |
19.4% |
5 |
33.3% |
0 |
0% |
0.104 |
|
≥18.5 |
29 |
80.6% |
10 |
66.7% |
11 |
100.0% |
||
|
Parameters |
Unadjusted (univariate) |
|
|---|---|---|
|
OR (95% CI) |
p-Value |
|
|
Age (≤50) |
0.954 (0.164–5.561) |
0.958 |
|
Sex (male) |
1.179 (0.342–4.063) |
0.794 |
|
Dietary habit (NV) |
1.750 (0.512–5.978) |
0.372 |
|
Socioeconomic condition (low) |
0.250 (0.062–1.038) |
0.056 |
|
Disease (ALL vs. AML) |
3.429 (0.969–12.137) |
0.056 |
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