Effect of stepwise nutritional intervention based on GLIM standard on children with leukemia undergoing transplantation: a retrospective study

Abstract

To evaluate the effect of stepwise nutritional intervention based on the Global Leadership Initiative on Malnutrition (GLIM) standard on children undergoing leukemia transplantation. A retrospective analysis was conducted on children who underwent leukemia transplantation. The study included two cohorts: one receiving stepwise nutritional intervention based on the GLIM standard, which had been formally incorporated into the routine nursing system during the study period, replacing the previous conventional nutritional nursing model, and the other receiving standard care prior to its introduction. Nutritional status, anthropometric measurements, biochemical indicators, and incidence of postoperative complications were assessed and compared between the two groups. Before and after receiving different nursing models, both groups showed improvements in albumin and hemoglobin levels; however, the increases were significantly greater in the nutrition intervention group than in the conventional group (P < 0.05). Similarly, weight, upper arm circumference, and triceps skinfold thickness (TSFT) increased in both groups, with significantly higher values observed in the nutrition intervention group (P < 0.05). Biochemical indicators, including albumin and prealbumin, also improved more markedly in the nutrition intervention group (P < 0.05). The overall incidence of postoperative complications was lower in the nutrition intervention group compared with the conventional group (df = 1, P = 0.086), but this difference was not statistically significant. The stepwise nutritional intervention based on GLIM standard can effectively improve the nutritional status of children undergoing leukemia transplantation and may be recommended for clinical practice.

Introduction

Leukemia is a malignant hematological disorder characterized by uncontrolled proliferation of abnormal white blood cells in the bone marrow, leading to impaired hematopoiesis, immune defense, oxygen transport, and hemostatic function¹. Hematopoietic stem cell transplantation (HSCT) is a key treatment option, yet patients frequently experience nutritional deterioration due to prolonged treatment and chemotherapy-related side effects such as nausea, anorexia, and gastrointestinal dysfunction². Malnutrition compromises overall health, reduces transplantation success, and delays recovery³. In children, leukemias and lymphomas account for nearly one-third of all pediatric cancers, and their heterogeneity further increases the need for effective supportive care, particularly nutritional management^4,5.

Among the various indicators of nutritional condition, serum proteins and hematological parameters are widely used in clinical practice. Albumin is a marker of protein reserves and overall nutritional adequacy, hemoglobin reflects oxygen-carrying capacity and erythropoietic function, and prealbumin provides a dynamic assessment of short-term nutritional changes^6,7. These markers, when interpreted together, offer valuable insights into both nutritional and metabolic status during the peri-transplantation period.

Malnutrition evaluation after allogeneic HSCT could be influenced by the tool adopted for screening or assessment⁸. The Global Leadership Initiative on Malnutrition (GLIM), established in 2019, provides standardized diagnostic criteria that integrate phenotypic measures (weight loss, low body mass index, muscle mass reduction) with etiologic factors (reduced intake, disease burden, or inflammation)⁹. This framework has been validated across diverse populations as a reliable tool for nutritional assessment and prognosis prediction, including in oncology and transplantation settings^10–12.

Stepwise nutritional intervention is a structured, individualized strategy that aligns with GLIM categories to guide staged management, ranging from dietary adjustment to oral supplementation and advanced nutritional support. This approach has been shown to enhance recovery, strengthen immunity, and improve long-term outcomes¹³. Based on this, the study incorporated data from pediatric patients with leukemia undergoing HSCT, comparing those who received care before and after the implementation of the GLIM-based stepwise nutritional intervention in our unit. The study assessed the impact of this intervention on nutritional status, treatment outcomes, and quality of life, thereby providing an evidence base for optimizing nursing strategies in this patient population.

Materials and methods

General information

A retrospective review was conducted of the clinical information for pediatric leukemia patients who underwent HSCT at our institution. The cohort included a control group receiving routine care prior to the introduction of the stepwise nutritional intervention model, and an intervention group (n = 43 in each group) enrolled after its implementation. The stepwise nutritional intervention based on the GLIM standard was a clinical routine nutritional nursing protocol newly developed and implemented by the Department of Hematology of our hospital in January 2022. This study represents a retrospective analysis conducted following the implementation of this protocol, rather than an intervention specifically designed for research purposes. Baseline demographic and clinical characteristics were compared between the two groups (Table 1), with no statistically significant differences (P > 0.05). The study protocol was reviewed and approved by the Institutional Review Board of CAPITAL CENTER FOR CHILDREN’S HEALTH, CAPITAL MEDICAL UNIVERSITY (Approval number: SHERLL2023074), in accordance with the Declaration of Helsinki. This was a retrospective study, and the requirement for informed consent was waived by the Ethics Committee.

Table 1.

Comparison of general characteristics between the two groups of patients (n (%), mean ± SD).

Group	Conventional group	Nutrition intervention group	t/x2	P
Number of cases (n)	43	43
Average age (years)	6.81 ± 2.13	6.70 ± 2.17	0.237	0.813
Disease duration (months)	3.09 ± 0.68	3.16 ± 0.72	– 0.464	0.644
Gender
Female	21 (48.84)	20 (46.51)	0.047	0.829
Male	22 (51.16)	23 (53.49)
Whether CR was achieved before transplantation
Yes	15 (34.88)	16 (37.21)	0.050	0.822
No	28 (65.12)	27 (62.79)
Whether the conditioning regimen includes TBI
Yes	9 (20.93)	10 (23.26)	0.068	0.795
No	34 (79.07)	33 (76.74)

P-values represent comparisons between the two groups. Age and disease duration were analyzed using independent-sample t-tests, for which both t- and P-values are reported. CR: Complete remission; TBI: Total body irradiation.

Inclusion criteria: ① Diagnosis of leukemia confirmed by bone marrow puncture; ② Undergoing hematopoietic stem cell transplantation in our hospital; ③ Availability of complete clinical data.

Exclusion criteria: ① Presence of severe comorbid organic lesions; ② Congenital metabolic disorders; ③ Concurrent severe behavioral or consciousness disorders; ④ Inability to take food or water, or requirement for parenteral nutrition; ⑤ Primary or secondary immunodeficiency; ⑥ Known history of severe allergy was recorded.

Intervention methods

In January 2022, the Department of Hematology of our hospital integrated the stepwise nutritional intervention based on the GLIM standard into the routine nursing system for children undergoing leukemia transplantation, replacing the previous conventional nutritional support model. In this study, the conventional group comprised children who received traditional routine care prior to protocol implementation, whereas the nutrition intervention group consisted of children who received the new routine care following protocol implementation.

Conventional group: Patients received routine care. Nursing staff closely monitored vital signs, implemented infection prevention measures, and promptly identified and managed post-transplant complications. A sterile environment was maintained with appropriate isolation, and attention was given to skin, oral, and gastrointestinal hygiene. Nutritional support was strengthened to ensure electrolyte balance and facilitate physical recovery. Regular assessments of complete blood count and immune function were performed to evaluate transplantation outcomes. In addition, psychological care was provided to address emotional needs and support adaptation to the treatment process.

Nutrition intervention group: A stepwise nutritional intervention based on the GLIM criteria was implemented.

① Preliminary screening: Nutritional risk was assessed according to the GLIM criteria, focusing on weight loss, reduced appetite, and inadequate intake. Standardized tools were used to evaluate nutritional status, and body mass index (BMI), weight change, and clinical symptoms (e.g., reduced muscle mass, poor appetite) were recorded.

② Clinical assessment: A comprehensive evaluation was conducted, including medical history, lifestyle, dietary preferences, and digestive/absorptive function. Key nutritional indicators such as serum albumin, transferrin, blood glucose, and blood urea nitrogen were monitored. Based on the assessment results, patients were classified into three categories: mild, moderate, and severe malnutrition.

③ Intervention phase: Nutritional interventions were implemented in stages according to the degree of malnutrition (Table 2).

Table 2.

Correlation between GLIM-defined malnutrition categories and stepwise nutritional interventions.

GLIM category	Criteria (examples)	Intervention step	Specific procedures
Mild malnutrition	Slight weight loss Reduced intake	Step 1	Dietary adjustments High-calorie, high-protein foods (e.g., whole milk, lean meat) Increased meal frequency and portion size Light physical activity after meals
Moderate malnutrition	Moderate weight loss Reduced muscle mass or intake	Step 2	Oral nutritional supplements (fortified drinks, powders) High-calorie, high-protein snacks between meals Adequate hydration with electrolytes Regular monitoring of serum albumin
Severe malnutrition	Severe weight loss Significant muscle mass reduction Severe intake reduction or disease burden	Step 3	Enteral nutrition (nasogastric/gastric tube) if feasible Parenteral nutrition if enteral contraindicated Monitoring of electrolyte balance, liver, and renal function

GLIM: Global Leadership Initiative on Malnutrition.

Mild malnutrition (first step): Dietary adjustments were prioritized to improve intake. High-calorie, high-protein foods (e.g., whole milk, lean meat) were added to ensure adequate energy and protein consumption. Meal frequency and portion sizes were increased, and food preferences were considered to enhance palatability and appetite. In addition, patients were encouraged to engage in light physical activity after meals to support digestion.

Moderate malnutrition (second step): If dietary adjustments were insufficient, oral nutritional supplementation was introduced under physician guidance. High-protein and high-calorie oral nutritional supplements (e.g., fortified drinks, nutritional powders) were provided to meet increased energy and nutrient demands. Additional nutritional snacks were offered between meals to enhance caloric intake. Adequate hydration was emphasized, including electrolyte-containing fluids to prevent dehydration. Nutritional markers, such as serum albumin, were regularly monitored to evaluate efficacy.

Severe malnutrition (third step): For patients whose nutritional requirements could not be met through oral intake, enteral or parenteral nutrition was initiated. Enteral nutrition (e.g., via gastric or nasogastric tube) was preferred when feasible, to ensure adequate caloric and protein intake. If enteral nutrition was contraindicated or insufficient, parenteral nutrition (intravenous nutritional support) was implemented. Electrolyte balance was closely monitored, and liver and renal function were assessed regularly to ensure the safety of nutritional support.

④ Family education: Caregivers were instructed to continue dietary management at home to ensure the continuity and effectiveness of nutritional support. Educational sessions were provided to enhance caregivers’ knowledge of nutritional interventions, including the preparation of balanced meals, adjustment of food types and portion sizes, and strategies to stimulate patients’ appetite.

⑤ Feedback mechanism: The effects of nutritional intervention were regularly evaluated and documented to guide subsequent adjustments. Feedback was provided to caregivers and patients, and individualized modifications were made based on clinical indicators and patient responses to ensure the sustained effectiveness of nutritional therapy.

Observation indicators

Relevant data were obtained from the hospital’s electronic medical record system. Standard laboratory techniques were employed as follows.

Nutritional status

Venous blood samples were collected from both groups to determine serum albumin and hemoglobin levels as indicators of nutritional status.

Anthropometric indicators

Body weight, mid-upper arm circumference, and triceps skin fold thickness (TSFT) were measured before and after the intervention. All measurements were performed by the same trained investigator to ensure data consistency. Each parameter was measured three times, and the average value was recorded to minimize measurement error and variability, thereby ensuring the reliability of the results.

Biochemical indicators

Fasting peripheral blood samples were collected at 8:00 a.m. to assess the levels of prealbumin and serum albumin.

Postoperative complications

The incidence of complications, including oral mucositis, bone marrow suppression, vomiting, and infection, was recorded.

Statistical analysis

Statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA) and R version 4.3.3 (R Foundation for Statistical Computing, Vienna, Austria). Categorical data were expressed as frequencies and percentages [n (%)], and inter-group comparisons were performed using the χ² test or Fisher’ s exact test. Continuous data were expressed as mean ± standard deviation (mean ± SD). Inter-group comparisons were performed using the independent-sample t-test, and intra-group comparisons were performed using the paired-sample t-test. A P value < 0.05 was considered statistically significant.

Research results

Nutritional status

Firstly, venous blood samples were collected to determine serum albumin and hemoglobin levels as part of the routine evaluation of nutritional status. Following the intervention, both groups of children exhibited increased levels of albumin and hemoglobin compared with baseline (Table 3). However, the nutrition intervention group demonstrated a significantly greater improvement in both albumin and hemoglobin levels than the conventional group, and the differences were statistically significant (P < 0.001).

Table 3.

Comparison of nutritional status between the two groups of children (mean ± SD).

Group	Conventional group	Nutrition intervention group	t	P
Number of cases (n)	43	43
Albumin (g/L)
Before intervention	22.38 ± 2.49	22.67 ± 2.44	– 0.546	0.587
After intervention	27.31 ± 3.25***	33.26 ± 3.83***	– 7.767	< 0.001
Hemoglobin (g/L)
Before intervention	85.56 ± 7.34	85.22 ± 7.90	0.207	0.837
After intervention	92.42 ± 9.38***	110.68 ± 9.65***	– 8.899	< 0.001

The independent-sample t-test was used for inter-group comparisons, and the corresponding t- and P-values were reported on the right. Pre- and post-treatment results were compared using the paired-sample t-test. Significance was denoted as ***P < 0.001 compared with before treatment.

Anthropometric indicators

After the intervention, both groups of children showed increases in weight, upper arm circumference, and TSFT. However, the improvements in the nutrition intervention group were significantly greater than those in the conventional group (P < 0.05) (Table 4).

Table 4.

Comparison of anthropometric indicators between the two groups of children (mean ± SD).

Group	Conventional group	Nutrition intervention group	t	P
Number of cases (N)	43	43
Weight (kg)
Before intervention	20.21 ± 9.30	20.11 ± 10.32	0.047	0.962
After intervention	24.23 ± 6.28*	29.87 ± 6.17*​**	– 4.201	< 0.001
Upper arm circumference (cm)
Before intervention	13.62 ± 4.36	13.76 ± 4.45	– 0.147	0.883
After intervention	15.31 ± 2.34*	17.72 ± 2.40***	– 4.712	< 0.001
TSFT (mm)
Before intervention	10.85 ± 3.26	10.93 ± 3.44	– 0.111	0.912
After intervention	12.11 ± 3.21	14.87 ± 3.25***	– 3.962	< 0.001

Note: The independent-sample t-test was used for inter-group comparisons, and the corresponding t- and p-values were reported on the right. Pre- and post-treatment results were compared using the paired-sample t-test. Significance was denoted as *P < 0.05 and ***P < 0.001 compared with before treatment. TSFT: Triceps skinfold thickness.

Biochemical indicators

Fasting peripheral blood samples were subsequently collected to enable a more sensitive evaluation of short-term nutritional changes. As shown in Table 5, both groups demonstrated increases in serum albumin and prealbumin levels following the intervention; however, the nutrition intervention group exhibited significantly greater improvements compared with the conventional group (P < 0.05).

Table 5.

Comparison of biochemical indicators between the two groups of children (mean ± SD).

Group	Conventional group	Nutrition intervention group	t	P
Number of cases (n)	43	43
Prealbumin (mg/L)
Before intervention	130.32 ± 62.21	128.41 ± 59.28	0.146	0.884
After intervention	166.86 ± 43.49**	189.36 ± 50.64*​​​​**	– 2.210	0.030
Albumin (g/L)
Before intervention	38.45 ± 2.65	38.53 ± 3.11	– 0.128	0.898
After intervention	40.26 ± 3.04**	44.37 ± 3.14*​​​​**	– 6.617	< 0.001
Total protein (g/L)
Before intervention	50.62 ± 6.34	50.54 ± 6.44	0.058	0.954
After intervention	56.38 ± 5.70*​​​​**	62.43 ± 5.42*​​​​**	– 5.044	< 0.001

Note: The independent-sample t-test was used for inter-group comparisons, and the corresponding t- and P-values were reported on the right. Pre- and post-treatment results were compared using the paired-sample t-test. Significance was denoted as **P < 0.01 and ***P < 0.001 compared with before treatment.

Postoperative complications

The overall incidence of complications in the nutrition intervention group was 9.30%, which was lower than the 25.58% observed in the conventional group. However, the difference was not statistically significant (df = 1, P = 0.086) (Table 6).

Table 6.

Comparison of postoperative complications between the two groups of children [n (%)]

Group	Conventional group	Nutrition intervention group	P
Oral mucositis	2 (4.65)	1 (2.33)
Bone marrow suppression	3 (6.98)	1 (2.33)
Vomit	2 (4.65)	1 (2.33)
Infect	4 (9.30)	1 (2.33)
Overall incidence	11 (25.58)	4 (9.30)	0.086

Fisher’s exact test was used to compare the incidence of overall adverse reactions between the two groups.

Discussion

Leukemia is a malignant hematologic disorder characterized by impaired hematopoietic differentiation and abnormal proliferation, resulting in compromised blood function and increased susceptibility to anemia and infection. Among pediatric patients, acute lymphoblastic leukemia (ALL) is the most common subtype, accounting for approximately 75% of cases under 15 years of age¹⁴, and leukemia stem cells, although few in number, are critical for sustaining long-term disease persistence¹⁵. Allogeneic HSCT remains the standard curative treatment and has been shown to improve disease-free survival, particularly in acute myeloid leukemia (AML)¹⁶. However, HSCT places children in a hypermetabolic state, increasing their risk of malnutrition, which can impair immune function, delay recovery, and predispose to complications. The GLIM has established widely accepted diagnostic criteria based on three phenotypic indicators and two etiologic factors, providing a standardized framework for nutritional assessment¹⁷. This investigation retrospectively evaluated pediatric HSCT recipients, comparing a cohort assigned to a stepwise nutritional intervention based on GLIM criteria with a control group on a conventional care pathway. The intervention yielded significant benefits, including marked enhancements in levels of albumin, prealbumin, hemoglobin, and anthropometric indicators, along with a reduced complication rate. The study conclusively highlights the efficacy of a systematic nutritional approach in improving clinical outcomes for children recovering from leukemia transplantation.

Albumin and hemoglobin are widely recognized as key biochemical indicators reflecting nutritional and inflammatory status¹⁸, while prealbumin is a sensitive marker of short-term nutritional changes^7,19. Insufficient protein or micronutrient intake (e.g., iron, vitamin B12, folate) can impair albumin and hemoglobin synthesis^20,21, leading to hypoalbuminemia or anemia, both of which weaken immune function, delay recovery, and increase the risk of complications^22,23. Children undergoing leukemia transplantation are at particularly high nutritional risk due to their hypermetabolic state and treatment-related side effects. In this study, stepwise nutritional intervention based on the GLIM standard significantly improved albumin, prealbumin, and hemoglobin levels compared with conventional care (P < 0.05), demonstrating enhanced protein synthesis, immune recovery, and overall nutritional status. Furthermore, the incidence of postoperative complications was lower in the stepwise nutritional intervention group (P < 0.05), indicating that structured nutritional support can reduce infection, bleeding, and organ dysfunction, thereby promoting recovery and improving clinical outcomes.

Recently, several studies have emphasized the importance of nutritional support in adult patients undergoing HSCT. For example, one study demonstrated that implementing a lactose-free diet, including lactose-free milk, significantly reduced the prevalence of vancomycin-resistant enterococci (VRE) carriers in allogeneic HSCT patients²⁴. In addition, nutritional intervention with TGF-beta–enriched food was shown to reduce malnutrition, as assessed by the Patient-Generated Subjective Global Assessment, and was associated with improved overall survival in allogeneic HSCT patients with a median age of approximately 55 years^25,26. Additional evidence indicates that patients at risk of malnutrition before transplantation had a higher risk of death during a 1-year follow-up, underscoring the need for multidisciplinary nutritional management. In contrast, in younger HSCT patients with acute leukemia (18–55 years), malnutrition did not significantly influence survival, mortality, or complications²⁷, suggesting that age and baseline risk profiles may modify the clinical impact of nutritional status. Compared with these prior studies, the present work provides novel evidence in a pediatric population, applying the GLIM criteria as a framework for stepwise nutritional intervention. This approach improved albumin, prealbumin, and hemoglobin levels, reduced postoperative complications, and promoted recovery in pediatric patients (median age 6.8 years). Collectively, these results emphasize the pivotal role of structured and targeted nutritional strategies in enhancing clinical outcomes across different HSCT populations.

Although this study demonstrated clinically meaningful results, several limitations should be acknowledged. First, the relatively small sample size and single-center retrospective design limit the evidence-level, generalizability and broader applicability of the findings. Second, this study focused on short-term outcomes without long-term follow-up record, making it difficult to evaluate the sustained impact of nutritional intervention on nutritional status and postoperative complications. Future multi-center studies with larger cohorts and longitudinal assessments are therefore warranted to validate and extend the present findings. Third, the potential confounding variables that were not fully controlled could have influenced the results. In addition, participants were not classified by leukemia subtype, restricting exploration of subtype-specific effects. Finally, while the GLIM criteria were applied as the framework for nutritional intervention, alternative assessment standards may yield varying results, underscoring the need for cross-standard comparative studies.

In conclusion, this study showed that the stepwise nutritional intervention guided by the GLIM standard can significantly improve the nutritional status, optimize biochemical indicators, and reduce postoperative complications in pediatric patients undergoing leukemia transplantation (Fig. 1). These findings suggest that such an intervention strategy should be actively integrated into clinical practice to provide more effective postoperative support and promote faster recovery in this population.

Fig. 1.

Schematic illustration of the stepwise nutritional intervention guided by the GLIM criteria in pediatric patients undergoing hematopoietic stem cell transplantation for leukemia.

Author contributions

We declare that all the listed authors have participated actively in the study and all meet the requirements of the authorship. CW designed the study, performed the studies, managed the data analyses and wrote the paper, NN & YLZ managed the study concepts and literature searches, BZ & SZ undertook the data acquisition. All authors reviewed the manuscript.

Funding

This research did not receive any specific funding.

Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study protocol was reviewed and approved by the Institutional Review Board of CAPITAL CENTER FOR CHILDREN’S HEALTH, CAPITAL MEDICAL UNIVERSITY (Approval number: SHERLL2023074), in accordance with the Declaration of Helsinki. This was a retrospective study, and the requirement for informed consent was waived by the Ethics Committee.