Introduction
Leukemia is the most common type of cancer in children (0–14 years old). In China, the incidence of childhood leukemia is 42.33 per 1 million [
1]. Of these, acute lymphoblastic leukemia (ALL) accounts for more than 70% of all acute leukemias in children. Although acute myeloid leukemia (AML) accounts for approximately only 25% of all pediatric acute leukemias, it is the second most common cancer type in children aged 5 years and older and in adolescents (aged 15–19 years) [
1]. In recent years, treatment outcomes for AML have improved due to precision risk stratification and optimized chemotherapy regimens, with overall survival reaching approximately 70% [
2,
3]. At present, an increasing number of studies have confirmed the link between the nutritional status of children at the initial diagnosis of acute leukemia and leukemia relapse and disease-related death [
4‐
9]. In addition, children are a special group, and we should not only focus on the issue of the length of their survival; the quality of life after cure is equally important. A significantly increased risk of obesity [
10,
11] and reductions in linear growth and final adult height [
12,
13] are common complications in cured children with ALL. However, studies of longitudinal growth changes among AML patients are rare [
6]. Malnutrition, obesity, and short stature seriously affect children’s physical and mental health [
11]. Therefore, it is imperative to pay more attention to the changes in body mass index (BMI), height and weight of children with AML during and after treatment and intervene in time.
In this study, we enrolled 88 patients in the Chinese Children’s Leukemia Group (CCLG)–AML2015 protocol at Beijing Children’s Hospital and evaluated BMI, weight, height and longitudinal changes in these measurements during and after therapy, along with the bone ages of patients and height of patients’ parents, to better predict the height of children. In addition, we analyzed the associations between leukemia outcomes and nutritional status at initial diagnosis and during treatment.
Discussion
Chemotherapy may affect the final adult height and nutritional status of children with leukemia, which in turn may affect the physical and mental health of patients after discontinuation of the drug [
11,
12]. Additionally, relatively high or low BMI may be associated with leukemia outcomes [
4‐
7]. Therefore, we evaluated the longitudinal changes in BMI, weight and height of 88 pediatric patients with AML during and after chemotherapy. We predicted the effect of chemotherapy on the final adult height of AML patients by the bone age and height of the patients’ parents. Moreover, we explored the associations between leukemia outcomes and BMI at initial diagnosis and during treatment. To our knowledge, this is the first study to use bone age and parental height in predicting the final height of children with AML. Meanwhile, this is the first study to use the growth curves of Chinese children and adolescents to assign descriptive values to BMI, weight, and height for children with AML, which minimizes the influence of different growth rates at different ages, genders and races on the results.
In this study, we found that during leukemia treatment, patients’ weight loss was mainly concentrated during induction and consolidation therapy, whereas the short-term effect of chemotherapy on height was not significant, resulting in reduced BMI in children during induction and consolidation therapy. The changes in weight are consistent with the current published AML study [
6]. After the maintenance period, the children’s weight and BMI gain were significantly accelerated, which is considered to be related to the low chemotherapy intensity and low tumor load after maintenance therapy. Over time, surprisingly, 20% of the children appeared to be overweight after two years of drug withdrawal, and we consider the high rate of overweight to be associated with chemotherapy drug effects and lack of exercise after cure. However, compared with the initial diagnosis BMI, there was no significant difference among the different treatment processes. This may be related to the fact that all children with leukemia in our hospital are equipped with a nutritious meal, narrowing the weight differences between treatment periods, or it may be related to the low sample size. Conversely, in patients with ALL, weight gain begins during induction therapy, which is the result of exposure to glucocorticoids and asparaginase, unhealthy diets, and lack of activity, and continues even after the end of therapy [
23,
24]. The difference in weight change between patients with ALL and those with AML underdoing intense chemotherapy could be attributed to disparities in their chemotherapy regimens. Notably, the administration of cytarabine [
25,
26] may induce stomatitis, contributing to weight loss in AML patients. Conversely, the use of glucocorticoids [
27] may lead to weight gain in ALL patients. As a high BMI can put survivors at increased risk of metabolic syndrome, early nutritional intervention and appropriate daily physical activity should be implemented in children with leukemia as early as possible [
28].
For height, our study found that the proportional change at each time point was not significant except at the two-year off therapy period. Height growth accelerated significantly after two years of drug withdrawal, and the majority of patients were in the 26-75% range of height for children of the same age and gender. Again, there was no significant difference between bone age and chronological age during and after treatment, and for the 12 patients who were followed up to their parents’ height, the height at last follow-up was within the range of the genetic prediction of height. However, one study [
6] on children with AML found that height Z scores are significantly lower than baseline scores not only during therapy but also throughout the off-therapy period, and linear growth is further affected by HSCT. The reason for the difference in the results of the two studies may be that our study excluded AML patients who underwent HSCT.
Our study found that patients with low BMI in the initial diagnosis and induction chemotherapy stages or with overweight in the initial diagnosis showed relatively lower 3-year EFS, 3-year RFS and 3-year OS. Previous studies also demonstrated that patients with AML in unhealthy BMI categories (underweight or overweight/obese) at diagnosis had significantly worse survival and more treatment-related mortality than healthy-weight individuals [
29,
30]. However, there was no significant difference in the effect of BMI on leukemia outcomes in our study. The revolutionary changes in AML treatment have marked small molecule inhibitors and biologic agents over the years [
31,
32]. Some supportive care, such as antibiotic prophylaxis, transfusion support, management of hyperleukocytosis and neutropenic fever, and better education for patient families and clinical staff, have also improved [
33,
34]. Patients with transplantation were excluded from this study, and most high-risk patients were excluded from the study, which would have resulted in prognostic bias. The above therapeutic advances and outcome bias due to enrollment criteria may have contributed to the outcomes being similar regardless of BMI status at diagnosis. In addition, the survival rate of children with AML in the present study was significantly higher than that of the reported studies [
2,
3], which is also considered to be related to the enrollment criteria. In addition, the small sample size of this study may also affect the
P value.
This study had some limitations. Because of death or transplantation, the number of patients declined over time. Most of the children were under 18 years of age at the time of the follow-up visit, and we had no information on whether patients had reached their final adult height. This study did not include the effects of confounding factors such as environment, diet, and exercise on height and weight. However, this study predicted the final height of children with AML by bone age and parental height and used the growth curves of Chinese children and adolescents to minimize the influence of different growth rates at different ages and sexes on the results, providing great clinical reference value.
Conclusion
In conclusion, this study revealed longitudinal changes in BMI, weight and height during the on-therapy and off-therapy periods, predicted the final height of children with AML by bone age and parental height, and demonstrated the relationship between BMI and leukemia outcomes. AML showed significant weight loss and decreased BMI during induction therapies, a gradual increase in weight and BMI after the maintenance period, and a greatly increased risk of overweight after discontinuation of chemotherapy, but treatment did not significantly affect the height of the patients with AML. Unhealthy BMI might reduce the prognosis of pediatric AML patients, but advances in leukemia treatment and supportive care have greatly reduced the prognostic impact of BMI at the time of the initial diagnosis. It is imperative to focus on the changes in BMI, height and weight of children with AML during and after treatment and intervene in time.
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