Elena J. Ladas

Purpose: Treatment for childhood ALL has been associated with sarcopenia and obesity in high-income countries (HIC); however, little is known about how treatment affects body composition or clinical outcomes for children receiving therapy outside HIC settings. Methods: In this prospective study, 60 children with ALL were followed from diagnosis through the first 6 months of therapy. Assessments included anthropometrics (BMI for age [BMI/a]) and body composition (dual-energy x-ray absorptiometry to derive appendicular lean mass index [ALMI] and fat mass index [FMI]), and clinical outcomes. Longitudinal changes in ALMI and FMI Z-scores were assessed using multivariable linear mixed-effects models. Results: The cohort was 56.7% female with a mean age of 10.2 ± 4.6 years; 26.7% were malnourished at diagnosis. BMI/a did not increase significantly over time. ALMI decreased significantly from diagnosis to month 6, whereas FMI increased significantly. Sarcopenia rose from 40% at diagnosis to 66.1% by the end of induction. No evidence of sarcopenic obesity was observed. Higher ALMI and FMI were each significantly associated with severe adverse events, whereas higher FMI was further associated with treatment delays and fewer hospital days. No association of nutritional status and survival was observed. Conclusion: Children with ALL in Guatemala exhibited distinct BMI/a trajectories compared with those reported in HIC, highlighting the influence of geographic, socioeconomic, and population-specific factors on treatment-related nutritional outcomes. Our findings may be beneficial in global settings where children of non-European ancestry represent a substantial proportion of patients. Further investigation is warranted to elucidate the underlying biological and contextual mechanisms and to inform context-appropriate nutrition interventions.

BACKGROUND: Asparaginase is essential for curing acute lymphoblastic leukemia (ALL), but its use is limited by asparaginase-associated pancreatitis (AAP), a severe and unpredictable toxicity lacking validated prospective biomarkers. We sought to define early systemic molecular features of susceptibility to AAP. METHODS: We performed longitudinal lipidomic and proteomic profiling in two independent pediatric ALL cohorts ( n = 161; 79 AAP cases, 82 controls) using paired blood samples collected before asparaginase exposure and at the end of induction therapy (including a single dose of asparaginase), thereby capturing pre-injury biology rather than consequences of pancreatitis. We applied differential abundance and network-based analyses and integrated lipid-cytokine associations using proteomics. RESULTS: Across cohorts, we identified a reproducible lysophosphatidylcholine-centered (LPC-centered) signature characterized by attenuated induction therapy–associated LPC responses and disruption of LPC coregulation at the network level. Proteomic profiling revealed enrichment of cytokine signaling pathways, and integrative analyses demonstrated altered lipid-cytokine coupling, including a flip in association direction for LPC species and IL-18 between cases and controls. Although IL-18/LPC ratios did not differ globally, elevated postinduction IL-18/LPC ratios identified AAP risk within a protocol-defined very high-risk ALL subgroup (AUC = 0.81). CONCLUSION: These findings support a systems-level model in which failure of coordinated lipid-immune responses under therapeutic stress confers vulnerability to AAP, providing a framework for validation and mitigation strategies. TRIAL REGISTRATION: NCT00400946; NCT01574274; NCT03020030 (parent trials). FUNDING: Servier Pharmaceuticals (IIT-95014-027-USA); SDRC (P30DK116074); Stanford SPARK; Fonds de Recherche du Québec – Santé; Fondation Charles-Bruneau; Leukemia & Lymphoma Society of Canada.

Background: Children with cancer in low‑ and middle‑income countries (LMICs) experience disproportionately high mortality. Nutritional care improves treatment tolerance and survival, yet access to trained nutrition professionals remains limited. The International Initiative for Pediatrics and Nutrition (IIPAN) was established to strengthen hospital‑based clinical nutrition services through capacity‑building, education, and mentorship. Objectives: To evaluate the IIPAN global clinical nutrition capacity‑building program across hospitals in LMICs. Methods: A monitoring and evaluation framework was implemented across 16 hospitals in 11 countries (February 2024–June 2025). Monthly indicators captured patient characteristics, nutritional status, delivery of nutrition interventions, and dietary diversity. Nutritional status was classified using body mass index (BMI)‑for‑age, mid‑upper arm circumference (MUAC), and height‑for‑age z‑scores based on World Health Organization standards. Findings: Across all sites, 29,295 clinical visits were reported. Most consultations occurred in inpatient settings (79.9%) and were follow‑up assessments (85.1%). Among patients, 52.5% had solid tumors and 39.6% had hematologic malignancies. Based on BMI‑for‑age, 10.3% were classified with severe acute malnutrition (SAM) and 13.5% with moderate acute malnutrition (MAM). Height‑for‑age analysis indicated that 27.2% were stunted. Nearly all hospitalized patients (95.8%) received a nutrition assessment within 24 hours of admission, and 96.0% received individualized or group nutrition education. Therapeutic foods or formulas were provided in 42.8% of consultations, while advanced nutrition therapy was administered in 3.5%. The prevalence of acute malnutrition decreased significantly between initial and follow‑up assessments (38.9% to 25.2%; P < 0.001). In sites with food kitchens, provision of therapeutic nutrition was substantially higher than program‑wide for both children consuming ≤50% of estimated needs (87.4% vs 55%) and for children with SAM (99.1% vs 86%). Conclusions: The IIPAN model demonstrates that integrated, hospital‑based nutrition care led by trained nutritionists can reduce acute malnutrition and improve access to essential nutrition services in LMICs.

Introduction: Typhlitis is a life-threatening complication of chemotherapy. The recommended nutritional management of typhlitis involves bowel rest and initiating parenteral nutrition (PN). However, in limited-resource settings, PN is not readily available, leaving patients who develop typhlitis without nutrition for prolonged periods. Strategies for the nutritional management of typhlitis in settings without access to advanced nutritional therapies are urgently needed. Case Presentations: Three patients with acute leukemia presented to Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa, Ethiopia, for treatment, where PN is unavailable. All three patients presented with acute malnutrition at diagnosis and developed typhlitis during chemotherapy. In each case, oral feeding was reintroduced prior to complete resolution of typhlitis, guided by improved bowel thickness, recovery from neutropenia, and resolution of gastrointestinal symptoms. Conclusion: Gradual reintroduction of oral feeding based on clinical indicators was successfully implemented across this case series, minimizing prolonged periods without oral intake and preventing further decline in nutritional status in the absence of PN. Drawing from this experience and the existing literature, we propose an algorithm to guide nutritional management during typhlitis in similar clinical contexts.

Non-communicable diseases (NCDs) affect over 2.1 billion children globally, accounting for 15.9% of deaths in children under 20 and contributing 174 million years lived with disability. Integrating nutrition care into NCD management within health systems can save lives, reduce costs, and improve quality of life. Nutrition interventions have been found to improve survival rates in children with cancer by 30%. Incorporating early nutrition interventions in hospitals is associated with a 36% reduction in per-patient costs. Despite these clear benefits, nutrition care is often not readily accessible as part of NCD management in children. Access to trained nutrition professionals is limited, and nutrition training for healthcare workers is often inadequate. There are cost-effective and scalable models for delivering high-quality nutrition care, but scaling these models will require commitment to capacity building, training, technological innovation, and monitoring frameworks. Coordinated, multisectoral responses are needed urgently to incorporate nutrition sustainably into healthcare systems to confront the growing burden of childhood NCDs.

Purpose The association of nutritional intervention and health-related quality of life (HRQL) was examined in children with cancer. Methods Undernourished children with cancer (N = 260) were randomized 1:1 to standard nutritional therapy (SNT) or SNT + Ready to Use Therapeutic Food (RUTF). HRQL was assessed using the Health Utilities Index® (HUI) at study entry and 6 weeks later. HUI has two systems, HUI2 and HUI3, with derived categories of disability. Scores after SNT and SNT + RUTF were compared. Results At study entry there were no significant differences in HRQL scores between the two treatment arms. After 6 weeks of nutritional intervention, median overall HUI2 scores were comparable—0.90 with RUTF and 0.89 with SNT (p = 0.317)—but overall HUI3 scores were 0.90 and 0.79 (p = 0.009), respectively. At study entry and 6 weeks, 87 (35%) and 116 (46.6%) subjects had no or mild disability, and 162 (65%) and 133 (53.4%) had moderate or severe disability (p < 0.001) respectively using HUI2 scores. Corresponding scores with HUI3 were 66 (26.5%) and 103 (41.3%) for no or mild disability and 183 (73.5%) and 146 (58.6%) (p < 0.001) for moderate or severe disability at study entry and 6 weeks, respectively. Children with weight gain >10% had significant improvement in overall HUI2 (0.92 vs 0.84; p = 0.049) and HUI3 scores (0.88 vs 0.78; p = 0.010). Conclusion In severely and moderately malnourished children with cancer, administration of RUTF and weight gain were associated with improved HRQL. Weight gain can improve HRQL in numerous domains and overall.

The survival rates for children with cancer have increased appreciably over the last few decades; however, childhood cancer survivors continue to suffer from long-lasting sequelae. Studies have demonstrated that the presence of malnutrition, over- and under-nutrition, at diagnosis or the duration of malnutrition during treatment is associated with increased toxicity, infection, and inferior survival. Dietary habits, along with behavioral and socioeconomic status, are known factors that lead to obesity or undernutrition and can affect the prognosis and quality of life of children with cancer. Unfortunately, the underlying mechanisms responsible for these observations are largely unknown. To address this gap in science, we established the EPICkids cohort study, an initiative of the International Initiative for Pediatrics and Nutrition at Columbia University Irving Medical Center and the International Agency for Research on Cancer of the World Health Organization. Over a 5-year period, children and adolescents with acute lymphoblastic leukemia and brain tumors receiving treatment in Spain, Italy, or Greece will be recruited. Clinical data and biospecimens (blood and stool) will be collected at designated timepoints in therapy. At the same time, several surveys will be administered to collect data on sociodemographics, physical activity, quality of life, food insecurity, and dietary habits. The primary aim of EPICkids is to develop a large informative nutrition biobank and database to investigate the etiologic pathways that connect nutritional status and lifestyle factors with clinical outcomes in children and adolescents with cancer. Secondary aims are to create evidence-based guidelines for European children with cancer in this understudied region and to ultimately improve the quality of life of those children and adolescents. The ClinicalTrials.gov ID for EPICkids study is NCT05375617.

Corrigendum of supplementary material only (supplementary material 1).

Introduction: This study investigated the prevalence of malnutrition at childhood cancer diagnosis in South Africa and the association with 1‐year post‐diagnosis overall survival (OS). Method: Nutritional status was prospectively assessed for newly diagnosed children with cancer. Chronic undernutrition was defined as two standard deviations (SDs) or more below zero for height/length‐for‐age (HAZ), and acute as underweight (weight‐for‐age [WAZ], and wasted as body mass index for age [BAZ] and mid‐upper arm circumference for age [MUAC/A]). The association between the nutritional status at diagnosis and age, sex, disease group and 1‐year post‐diagnosis OS was analysed with Cox regression and hazard ratios (HRs). Results: Less than 15% were chronically malnourished (stunted: 14.3%) and up to 24.3% acutely undernourished (wasted: 24.3% MUAC‐Z and BAZ 8.1%), 11.6% underweight, of 320 patients at cancer diagnosis). More females than males were underweight (12.2% vs. 4.5%; p = 0.027). Children of 5 years of age and older had a higher prevalence of wasting (18.7%) than children under 5 years of age (3.9%) ( p < 0.001) at diagnosis, with significant improvement 6 months after diagnosis. Stunting was significantly associated with poorer OS at 3 years after a cancer diagnosis (HR 1.8; 95% CI 1.1, 2.8; p = 0.011). Conclusion: MUAC/A identified more children with undernutrition than other nutritional parameters. Stunting was significantly associated with poorer OS 3 years and EFS 2 years after a cancer diagnosis. Optimal nutritional support should be provided for South African children, especially those with acute and chronic malnutrition, to improve OS.