Association of Low Height with Low Weight Presented During Chemotherapy Treatment in Pediatric Patients in Remission of Acute Lymphoblastic Leukemia (ALL)

Childhood Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer in the world, but especially in developed countries, it is a malignant disease of the white blood cells with a multifactorial etiology that involves an interaction of environmental, genetic and nutritional factors . It is estimated that more than 60% of the patients diagnosed with ALL are children under 15 years of age, with an incidence at 2-5 years [1-3]. 

Currently ALL treatments use several antineoplastic drugs that have greatly improved survival rates because of more effective treatments for childhood cancer. Unfortunately, the improved prognosis has been accompanied by the development of late complications related to treatment [4]. 

One of the most important aspects that must be taken into account during the treatment of ALL is the nutritional status and low weight of the patients, this is a condition that results from the balance between food intake and the body's expenditure to provide energy. In developing countries [5], such as Mexico, around 50% of pediatric patients with some type of cancer at the time of diagnosis have malnutrition and of all diagnosed cancers, ALL stands out with 20 to 50% of patients with malnutrition or underweight [6,7]. 

Adequate nutrition during cancer plays a decisive role in several measures of clinical outcome, such as response to treatment and quality of life after illness [8]. In childhood cancer patients, malnutrition has been proposed to increase infection rates and reduce survival [9]. There is evidence that malnutrition or underweight at an early age can cause a child's loss of development. Some studies explore the implications of suffering from childhood malnutrition and growth recovery for adult body size, but also for bone strength [10,11]. 

It is well known that the mechanism of action of some antineoplastic and cytotoxic agents used in the treatment of ALL can be altered in their pharmacokinetic behavior due to malnutrition or nutritional status [12,13] and as a consequence can cause negative effects and lead underweight or even malnutrition of the patient [14]. Malnutrition is a critical predictor of toxicity and outcome in cancer patients and may be perceived differently by patients, family members, and physicians [15,16]. 

Poor nutrition during growth and development in the pediatric stage can cause short stature as a consequence of the arrest of growth and development [17-19], therefore we decided to carry out this study, which is focused on determining if the short stature of a group of 39 patients under surveillance could be associated with the low weight and disease status they suffered during their ALL chemotherapy protocol.

The Research Ethics Committee and the Research Committee of the General Hospital of Durango Torre Materno-Infantil, Mexico, approved and validated the study in accordance with the Declaration of Helsinki and the General Health Law of Mexico. 39 pediatric patients of both sexes were studied at the Pediatric Hemato-Oncology Service of the State Oncology Center (CECAN) of the Ministry of Health of Durango, Mexico. All patients were diagnosed with ALL according to the criteria of the French-American-British Hematology Association [20]. Each patient underwent chemotherapy treatment according to the St Jude TOTAL XV protocol [21], none had craniospinal radiotherapy. Children who had completed their treatment protocol, that is, they were on surveillance. In addition, a group of 39 children without ALL were matched for age and sex and were evaluated as a control group. All the parents of the patients were asked to sign the informed consent, in addition to the children older than 8 years, they were asked to accept the informed consent.

The associations of the demographic aspects between the groups of cases (patients with ALL) and the controls (patients without ALL) were compared using the Chi-square test, the value <0.05 was considered significant. Comparison between patients with ALL with and without short stature was carried out by means of a chi-square test (x2) where a value of p=<0.05 was considered significant. The determination of the risk of patients with leukemia to have short height was determined by means of an Odds Ratio test, p<0.05 was considered significant. Finally, the multivariate analysis was performed with a correspondence test, using the TIBCO Statistica 13.3 software [22,23] (Graph 1). 

Graph 1: Two-dimensional graph that includes the cases (o), as well as the 8 variables (o).

Note: The variables that presented the greatest association are low height (relative inertia: 0.19944), male gender (Sex F) (relative inertia: 0.17984) and low BMI (relative inertia: 0.10641).

Tables 1 shows the comparison of the demographic aspects of children with ALL with and without short stature. We can see that there are no significant differences in the age of the patients (p=0.8), on another hand, we can see that there are a significant differences in the weight (p=0.002), height (p=<0.00001) and BMI (p=0.00009). Table 2 shows us the comparison between patients with ALL and without ALL with low height, we can see that there is a significant difference between the patients with ALL and without ALL with low height p=0.0006. 

Table 1: Comparison of the demographic aspects of children with ALL with and without low height.

Note: *Chi-square. 

Table 2: Comparison between patients with ALL with and without low height.

Note: *Chi square test. X²=11.5461 

The case-control study shows us that patients with ALL have a higher risk of being short (OR: 5.7273, 95% CI: 2.1623 to 15.1701, p=0.004). 

Finally, with the multivariate analysis we can observe that of the different variables that patients with ALL present, the ones that were most associated with them were: low height (relative inertia: 0.19944), female sex (Sex F) (relative inertia: 0.17984) and low BMI (relative inertia: 0.10641).

There are several studies that talk about the importance of good nutrition for proper development, as well as how significant it can be for a child to have low weight since it is in full development, this becomes especially important in pediatric patients with some type Of cancer. Rogers PC [24], shows this in his study where he points out the importance of this aspect since childhood is a moment of total development in a person's life. 

Iniesta RR et al. [25] and Arpaci T et al. [26], make it clear that if a child suffers from malnutrition or underweight, it may suffer certain adverse effects on its development, which is evidenced in our work by making it clear that low weight possibly caused by ALL and treatment for this disease affected the development of height in patients who have completed their treatment. 

The influence of sex on nutritional status has been mentioned by different authors. Castel H et al. [27], Nätt D et al. [28], y Marino M et al. [29], point out in their different studies the influence of sex on malnutrition, they mention that for different causes such as the ovarian cycle and physiological differences, women indicated that they were more prone to malnutrition, however these studies were conducted in healthy patients without any disease. Tazi I et al. [30], Joffe L et al. [31], y Aarnivala H et al. [32], point out in their studies the association of patients with malnutrition and low weight who suffered from different types of cancer including ALL, mostly women, this coincides we found this in our study, since although the population of patients with ALL has more men than women, women had a greater risk of being underweight, so special attention is recommended.

According to the results obtained, it was found that patients with ALL have a higher risk of having low height after concluding treatment; In addition, the multivariate analysis showed that patients with ALL and low weight were associated with short stature, female sex, and low BMI. 

Therefore, we assume that low weight may be caused by the disease and/ or antineoplastic treatment and consequently the short stature of patients with ALL. 

Therefore, it is necessary to evaluate more variables to know if patients suffer from some type of malnutrition, since the diagnosis of ALL before the pubertal outbreak, the use of steroids and the development of metabolic disorder can be decisive for the final short stature.