Effect of Nutritional Screening in Children with Acute Lymphoblastic Leukemia Undergoing the Maintenance Chemotherapy

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Methods: The reviews of 1038 pediatric patients were retrieved for the retrospective, propensity score-matched, superiority study. A 1:1 propensity score matching was utilized to match patients who received nutritional screening (screening cohort) to those who remained usual care without screening (control cohort). The primary endpoint was the long-term event-free-survival(EFS) after the last cycle of maintenance. Secondary outcomes included immune function, complications and long-term quality-adjusted life years (QALYs). Results: The proportion of cases with risk of malnutrition in screening was 25.8%. At the end of 4 weeks following the last cycle, the level of serum albumin was higher in screening cohort than control cohort (p<0.001), while the cellular immune function significantly improved in screening cohort (all p<0.05). During a mean of 11.09±6.45 months follow-up, 28.6% of patients in screening cohort had an event including ALL-related emergency visits, readmitted hospitalizations and severe infections compared to 46.5% of cases in control cohort yielding a hazard ratio of 0.397 (95%CI: 0.306, 0.493 and a significant difference in long-term EFS (24.07 (95%CI: 23.09, 25.04) vs. 18.02 (95%CI: 16.62, 19.42), log-rank p<0.001). The means of QALYs calculated by area under the curve up to 3, 6, 12 and 24 months after discharge were significantly lower in screening cohort as opposed to control cohort (all p<0.05). Conclusions: Pediatric ALL receiving the specific-for-children nutritional screening during hospitalization exhibited a better EFS over the 24-month follow-up than cases without screening. The benefit accounted for a significant improvement in immune function and QALYs scores over long-term follow-up. acute lymphoblastic leukemia nutritional screening event-free-survival readmission infection quality-adjusted life years Figures Figure 1 Figure 2 Figure 3 Introduction Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in child, accounting for the world age-standardized incidence of 46.4 per million per year in children aged 0–14 years and 28.5 per million in adolescents aged 15–19 years 1 . The cancer registration data show the same trend in China 2 . Chemotherapy remains the standard treatment for pediatric ALL, which usually has three phases-induction, consolidation and maintenance over the course of several years, with the 5-year survival rate can be over 80% 3, 4 . However, the severity of post-treatment myelosuppression increases as the frequency and intensity of chemotherapy rise, leading to the vulnerability of malnutrition. Adverse reactions to aggressive chemotherapy drugs and emotional instability also result in a diminished appetite in patients 5 . In addition, corticosteroids, integral component of ALL maintenance treatment are also likely contributors to impact children’s ability to take normal diet, thus contributing to a further decrease in nutritional status during the final and longest maintenance treatment stage 6 . In turn, patients with nutritional deficiencies have impaired haemopoietic and immune functions 7 , 8 . These evidences suggest that under-nutrition have been emphasized to be closely correlated with clinical efficacy, chemotherapy tolerance and prognosis in cases of ALL 9 . Furthermore, malnutrition decreases quality of life and prolongs length of hospital stay 10 . It is well known that the European Society for Clinical Nutrition and Metabolism (ESPEN) expert group emphasized the screen cancer patients for nutritional risk early in the course of their care 11 . Although malnutrition risk at the induction or intensification chemotherapy was significantly higher in patients who were not in remission than in the patients at any time during the maintenance therapy, previous research emphasized longitudinal changes of nutritional status in childhood cancer is a dynamic process, therefore, clinicians should follow up closely with re-evaluation required at each phase of treatment, among which maintenance is the last phase, indicating to prevent relapse of the disease and lasting for around 2–3 years 9 . Previous studies addressing this aspect from different parts of world has been reported, whereas, there is a lack in Chinese children with ALL, which might due to the absence of a gold standard measure 12 , 13 . Recently, the Subjective Global Nutritional Assessment (SGNA) represented a simple, comprehensive, organized and non-invasive, tool in pediatric patients, which has been proved to be highly sensitive tool for assessing nutritional status and identify children at risk of developing malnutrition with good inter-observer reliability and for prediction of post-operative adverse events 14 . Due to the limited evidences regarding its clinical use, the study aimed to evaluate the effectiveness of implementing the routine nutritional screen to identify “at risk” nutritional status in children diagnosed with ALL on maintenance therapy, that followed by a referral to the specialists in the nutrition department of our hospital for early nutritional intervention, to influence the event-free survival (EFS) and quality-adjusted life years (QALYs) during long-term follow-up. Methods Study design and participant selection The institutional Ethics Examining Committee of Human Research (TZRMH-2025KY-008) authorized ethical approval for a retrospective propensity score-matched cohort study in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines based on the principles of the Declaration of Helsinki 15 . Informed consents were waived for adult patients, because all data were retrieved from the existing medical and administrative records to inform treatment. No patients were contacted for the study and no personal data were disclosed. Whereas, informed consents were obtained from the parents or legal guardians for participants younger than the age of 16 after enrollment. Between January 1, 2020 and February 28, 2024, the reviews of pediatric patients who admitted to our hospital for the treatment of ALL according to the South China Children’s Leukemia Group-ALL-2015 protocol were extracted from the electronic medical records (EMRs) 16 . Inclusion criteria were as follows: ⑴ confirmed diagnosis of ALL by the criteria from the 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukmia 17 ; ⑵ aged 0 to 18 years of age at diagnosis; ⑶ on maintenance chemotherapy using 6-mercaptopurine 50mg/m 2 every day and methotrexate 25 mg/m 2 one day per week according to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (version 2.2021) 18 . Patients were excluded due to Philadelphia chromosome–positive ALL, relapsed/refractory disease, down syndrome, pulmonary/bone metastasis, neuromuscular disease, severe metabolic disease or gastrointestinal disease; hepatic or renal dysfunction and incomplete data. The review of 515 consecutive patients who were identified as the screening cohort were retrospectively retrieved from the electronic medical records (EMRs). We performed a propensity-score matching analysis of patients, who did not receive nutritional screening over the same period, in a 1:1 ratio as control cohort. The score was estimated using the baseline variables by the nearest-neighbor method with a caliper of 0.20: ⑴ age; ⑵ gender; ⑶ ALL immunophenotype; ⑷ Karyotye analysis; ⑸ white blood cell (WBC) count at diagnosis; ⑹ ALL risk category based on the International Berlin-Frankfurt-Munster Group Study Group and IntReALL Consortium risk classification 19 ; ⑺ end of induction-measurable residual disease (EOI-MRD); ⑻ post-induction condition; ⑼ extramedullary disease; ⑽ central nervous system leukemia (CNSL); ⑾ prednisone response; ⑿ serum albumin and body mass index (BMI) on the first day of admission. Nutritional screening Given that nutritional screening was not a routine procedure, the patients were engaged to selecting the management option most closely aligned with his/her values and preferences. Within 48 hours upon admission, patients were screened for nutritional risk using SGNA questionnaire, which has been widely used for more than 20 years to screen the nutritional status for pediatric patients, who are hospitalized, with neurocognitive disabilities or chronic illness/disease. The screening was performed by specially trained nurse staff at each cycle of maintenance for patients with agreement. Cases with a positive screening result were prescribed to a dietitian for detailed assessment to produce an early nutritional intervention or support. Outcomes measurement The SGNA nutrition-screening tool uses both subjective and objective nutrition-focused aspects to identify nutritional status, considering seven specific features of medical history (height-for-age, weight-for-height, changes in body weight, adequacy of dietary intake, gastrointestinal symptoms, functional capacity, and metabolic stress of disease) and three parameters of physical examination (loss of subcutaneous fat, muscle wasting, and edema) for signs of inadequate energy and/or protein intake. A child’s nutritional status is categorized in accordance with the SGNA rating form as ⑴ normal/well nourished: The patient is growing and gaining weight normally, has a grossly adequate intake without gastrointestinal symptoms, shows no or few physical signs of wasting, and exhibits normal functional capacity. Normal ratings in most or all categories, or significant, sustained improvement from a questionable or moderately malnourished state. It is possible to rate a patient as well-nourished in spite of some reductions in muscle mass, fat stores, weight and intake. This is based on recent improvement in signs that are mild and inconsistent. ⑵ moderately malnourished: This patient has definite signs of a decrease in weight and/or growth, and intake and may or may not have signs of diminished fat stores, muscle mass and functional capacity. This patient is experiencing a downward trend, but started with normal nutritional status. Moderate ratings in most or all categories, with the potential to progress to a severely malnourished state. ⑶ severely malnourished: This patient has progressive malnutrition with a downward trend in most or all categories. There are significant physical signs of malnutrition—loss of fat stores, muscle wasting, weight loss >10%—as well as decreased intake, excessive gastrointestinal losses and/or acute metabolic stress, and definite loss of functional capacity. Severe ratings in most or all categories with little or no sign of improvement 20 . The levels of serum albumin (ALB), prealbumin (PA) and retinol binding protein (RBP) were measured from fasting blood specimens. The levels of T-cell subsets in peripheral blood were detected by immunofluorescence and flow cytometry to calculate the percentage of natural killer (NK) cells as immune indicators. Length of hospital stay (LOS) was predefined as days from admission to discharge from the ward, and prolonged LOS was considered as LOS>8 days. Early readmission was defined as readmission to hospital within 30 days post-discharge due to all-cause. The health-related quality of life (HR-QoL) was evaluated using the QALYs, which were calculated using the European quality of life five-dimensional (EQ-5D-5L) utility values over time following the area under the curve (AUC) method. The EQ-5D-5L questionnaire contained five domains: mobility, self-care, usual activity, pain or discomfort and anxiety or depression. Each dimension is scored using a 5-points likert scale, depending on whether the respondent has no, slight, moderate, severe or extreme problems. Utility scores were calculated by the Euro-QoL crosswalk set of utility index values to their EQ-5D-SL health states. The QALYs were generated via the AUC when the utility scores were plotted over time 21 . Data on demographic and other clinical data were retrieved from EMRs, SGNA scores and QALYs scores were extracted from medical database, which were collected through telephone interview by specially trained nurses according to our clinical protocol. The primary endpoint was the long-term survival without events that required acute care during long-term follow-up, defining as ALL-related emergency visits, readmitted hospitalizations and occurrence of severe infections. Sample size calculation PASS statistical software, version 22.0 (NCSS, LLC. Kaysville, Utah, USA) was used for sample size calculation. Based on a multidisciplinary experts’ consensus from a series of cases discussion, an equal sample allocation superiority was designed to compare the hazard rates of ALL-pediatric patients receiving a routine nutritional screening to those without screening using a log-rank test. The hazard rate was supposed to be 2.0, we wanted to show that it decreased by at least 25% when the nutritional screening was performed, which was considered to be clinically better for EFS of ALL 22 . We wanted to compare sample size when the power was 0.80 with two-side type I error of 5%, and the difference in hazard rates was between − 0.8 and − 0.3, specifying the value of the clinical superiority margin by 0.5. If the data-loss rate was estimated to be 20% in both two cohorts, the sample size was 587 cases in either screening or control cohort. Statistical Analysis SPSS software version 22.0 (SPSS Inc, Chicago, IL) was used for statistics analysis. Significant level was reported as p < 0.05. Data normality was performed using Kolmogorov-Smirnov Z test. Nominal distributed data, non-normally distributed data and categorical data were recorded as mean ± standard deviation (SD), median ± inter quartile range (IQR) and percentage. Differences between groups were compared using the student t test, Mann-Whitney U test and Chi-squared test. The probability of EFS was evaluated by the Kaplan-Meier method, and differences among cohorts were assessed by log-rank analysis with 95% confidence interval (CI). The censored point was defined as disease-free survival at the last follow-up assessment. Results Figure 1 showed the cohort flow diagram, a total of 1174 pediatric patients with ALL were identified for this study cohort. After propensity score matching, the screening cohort included 515 cases and 523 in the matched cohort. Table 1 showed the demographic and clinical characteristic of patients at baseline, which were well balanced between the two study cohorts. A total of 74.2%, 19.4% and 6.4% of cases in the screening cohort were respectively categorized as being at normal/well, moderately and severely malnourished during their maintenance treatment based on the SGNA nutritional screening tool for malnutrition risk. Occurrence of hypoproteinemia was reported in 11.1% and 31.5% cases in screening and control cohort at 4 weeks post-discharge, with significant between-group differences (p 8 days, compared with 40.1% of cases in control group (p < 0.001). As shown in table 2, the levels of ALB, PA and RBP were significantly higher in screening cohort at 4 weeks after the last maintenance cycle (all p < 0.05), while the lower in screening cohort as compared to the matched cohort at 4-week post-discharge following the last maintenance cycle (all p < 0.05). There were 26.8% of patients in screening cohort reporting ALL-related events requiring acute care as compared to 46.5% of cases in control cohort (p < 0.001) according to the Kaplan-Meier curves showed in Fig. 2 . Specifically, there were significantly lower proportion of patients in screening cohort in ALL-related emergency room visits (7.0% vs. 24.3%, p < 0.001), re-hospitalization (13.2% vs. 28.5%, p < 0.001) and severe infection (6.6% vs. 13.6%, p < 0.001) as opposed to those in control cohort during the long-term follow-up. Superiority was met, as the hazard ratio of the primary outcome was 0.397, the 95% confidence interval of 0.306 to 0.493 which felt within the predefined superiority margin of 0.5. As a matter of fact, the mean of long-term EFS was significantly longer in patients receiving nutritional screening than those as controls (24.07 (95%CI: 23.09, 25.04) vs. 18.02 (95%CI: 16.62, 19.42), log-rank p < 0.001). Figure 3 illustrated the quality of life between the two groups using the EQ-5D-5L utility and the corresponding QALYs over the long-term follow-up. There was a trend to reduction in the mean of QALYs for patients in both two groups. However, the means of QALYs calculated by AUC up to 3 (20.94 ± 12.64 vs. 17.33 ± 3.18, p = 0.039), 6 (29.12 ± 13.64 vs. 17.91 ± 3.86, p = 0.016), 12 (34.95 ± 15.59 vs. 20.45 ± 4.05, p = 0.009) and 24 months (39.12 ± 16.17 vs. 21.03 ± 14.36, p = 0.001) after discharge were significantly lower in the combined screening group as opposed to the matched control group. Discussion The present study firstly examined the long-term consequence of post-discharge EFS in relation to an implementation of routine nutritional screening for pediatric patients with ALL undergoing the maintenance chemotherapy. Our findings confirmed that the long-term EFS rate had been significantly improved in screening cohort, the average gain in immunocompetence and QALYs was higher for patients receiving nutritional screening as compared to matching control cohort, which might attribute to accurate assessment of nutritional status for early intervention of pediatric patients. Evidences revealed that the composition of pediatric body composition including bone density, fat- and fat-free mass and total body water, are changed primarily by caner itself, aggressive multimodal treatments, metabolism changes, unbalanced diet and physical activity reduction, influencing the patient’s nutritional status 23 . In turn, nutritional status disorders can modify the metabolism, volume distribution and clearance of chemotherapy, then change the drug pharmacokinetics to impair the effectiveness of cancer treatment and alter the cytokine hormone function to decrease the ability of immune response against infection 24 . Malnutrition adversely affects several clinical outcomes in terms of disease progression, survival, treatment-related morbidity and risk of infection. Likewise, it has been proved to be associated with a poor health-related quality of life 25 . The proportion of nutritional status disorders with pediatric ALLs at diagnosis ranges from 6–21.2%, and increased to 52.6% after at least one chemotherapy cycle 26 . As result, a systematic and standard approach of screening for nutritional status with adequate tool should be offered to all pediatric patients with ALL, which could be intervened upon to improve their clinical outcomes. In the present study, we employed a validated method for the overall pediatric population to identify the nutritional risk among the study population, which was not taken as a routinely reported practice up to now. Of the 515 cases in screening cohort, normal nutrition were reported in 74.2% of cases, moderate malnutrition in 19.4% and severe malnutrition in 6.4%, which was consistent with the previous reported median prevalence of undernutrition ranging from 10.3–20% at last maintenance cycle 27 . Although meeting the nutritional requirements in these pediatric cancer population is challenging, the enteral or parenteral nutritional support is frequently used to effectively reverse malnutrition associated with the anti-neoplastic treatment, promote treatment tolerance and improve immune function 28 . Yueqin Han et al estimated the application of nutrition therapy in childhood ALL during chemotherapy, their results showed the concentrations of ALB were significantly increased, while the percentages of CD3+, CD4+, CD4+/CD8+, NK cell significantly decreased at 4 weeks post-treatment 29 . In this study, we also found a significantly better improvement of immune function in screening cohort than control cohort. In contrast, patients with a malnourished status assessed by the SGNA were 1.95-time (95%CI: 1.12, 3.39) more likely to be readmitted as opposed to the well-nourished (p = 0.017) 30 . Moreover, malnourished ALL-children had 2 to 3 times prone to suffer from infection compared to well nourished (p = 0.024), and thus prolonged the duration of treatment, hospital stay, even could lead to death 31 . Consistent with previous evidences, our Kaplan-Meier survival analysis in screening cohort indicated a significantly greater outcome of the long-term probability of EFS than those did not receive screening for malnutrition risk in control cohort, which were in line with a meta-analysis concluding that malnutrition was associated with poorer overall survival (RR = 1.36 (95%CI: 1.16, 1.60) and EFS (RR = 1.56 (95%CI:1.32, 1.86)), respectively, supporting the essential to recognize and achieve optimal nutritional status by nutrition intervention to improve treatment results in pediatric ALL 32 . In addition, the implementation of a routine nutritional screening had a significantly markable impact on QoL over 24 months with a greater QALY score as opposed to control cohort without screening, which indicated that the routine nutritional screening was a useful process to distinguish the risk of malnutrition for pediatric patients with ALL, and minimized the delay in referral to a dietitian for early diagnosis and intervention to achieve a better nutritional status, therefore, further improved HR-QoL over time. Similarly, previous reviews showed nutritional assessment and early intervention in pediatric patients with caners could significantly improve their HR-QoL 25 . This study has several limitations. First, it was a single-center design, which limited its generalizability to all hospitalized pediatric ALLs. Second, investigators responsible for outcome assessment were not blinded due to the nature of retrospective study, which might yield confounding bias. Third, although our hospital the largest tertiary center in the city, we did not capture all readmissions for cases in our cohort, because patients were likely to be readmitted in other medical centers. Four, we did not measure the micronutrients in both the cohorts. In the future, there is a need for a well-designed, randomized, controlled study to verify our results. In conclusion, the implementation of routine nutritional screening in pediatric ALL patients could significantly improve the long-term ESF, when defining ALL-related events as ALL-related emergency visits, readmitted hospitalizations and occurrence of severe infections, and accounted for a significant improvement in scores of QALY over long-term follow-up. Abbreviations ALL acute lymphoblastic leukemia EFS event-free-survival QALYs quality-adjusted life years SGNA Subjective Global Nutritional Assessment EMRs electronic medical records EOI-MRD induction-measurable residual disease BMI body mass index HR-QoL health-related quality of life EQ-5D-5L European quality of life five-dimensional LOS length of hospital stay AUC under the curve SD standard deviation IQR inter quartile range CI confidence interval. Declarations Ethic approval and consent The ethic was approved by the institutional Ethics Examining Committee of Human Research (TZRMH-KY-2025015) based on the principles of the Declaration of Helsinki. Informed consents were waived for adult patients, because all data were retrieved from the existing medical and administrative records to inform treatment. No patients were contacted for the study and no personal data were disclosed. Whereas, informed consents were obtained from the parents or legal guardians for participants younger than the age of 16 after enrollment. Clinical trial number Not applicable。 Data availability statement The data are available from the corresponding author upon reasonable request. Acknowledgments None Conflicts of interest The authors declare no conflicts of interest in this study. Funding statement None. Author contributions statement Caihong Fu was involved in the conception and design, analysis and interpretation of the data; the drafting of the paper, revising it critically for intellectual content; and the final approval of the version to be published. Xin Xu was involved in the conception and design, analysis and interpretation of the data; the drafting of the paper, revising it critically for intellectual content; and the final approval of the version to be published. Xuefen Zhao was involved in the conception and design, analysis and interpretation of the data; the drafting of the paper, revising it critically for intellectual content. Juan Wang was involved in the conception and design; the drafting of the paper, revising it critically for intellectual content. Li Chen was involved in the conception and design; the drafting of the paper, revising it critically for intellectual content. And all authors agreed to be accountable for all aspects of the work. References Steliarova-Foucher E, Colombet M, Ries L, Moreno F, Dolya A, Bray F, et al. International incidence of childhood cancer, 2001-10: a population-based registry study. LANCET ONCOL. 2017;18:719–31. Zheng R, Peng X, Zeng H, Zhang S, Chen T, Wang H, et al. Incidence, mortality and survival of childhood cancer in China during 2000–2010 period: A population-based study. CANCER LETT. 2015;363:176–80. Cooper SL, Brown PA. Treatment of pediatric acute lymphoblastic leukemia. 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Nutritional Status of Pediatric Cancer Patients at Diagnosis and Correlations with Treatment, Clinical Outcome and the Long-Term Growth and Health of Survivors. CHILDREN-BASEL. 2020;7. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 07 Jun, 2025 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 21 Apr, 2025 Reviews received at journal 19 Apr, 2025 Reviews received at journal 16 Apr, 2025 Reviewers agreed at journal 15 Apr, 2025 Reviewers agreed at journal 13 Apr, 2025 Reviewers invited by journal 13 Apr, 2025 Submission checks completed at journal 12 Apr, 2025 First submitted to journal 09 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6248851","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":443733205,"identity":"f78602ea-3e89-480d-86d1-ec80fd7370c6","order_by":0,"name":"Xuefen Zhao","email":"","orcid":"","institution":"Children’s Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xuefen","middleName":"","lastName":"Zhao","suffix":""},{"id":443733206,"identity":"8217db1f-6eac-4799-b7e9-d84e5bc3388d","order_by":1,"name":"Juan Wang","email":"","orcid":"","institution":"Children’s Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Wang","suffix":""},{"id":443733207,"identity":"8cb9e90a-2dbd-4775-9ec9-c4c92810c9a3","order_by":2,"name":"Li Chen","email":"","orcid":"","institution":"Children’s Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Chen","suffix":""},{"id":443733208,"identity":"b81ede40-3970-460d-b26c-90ae7ba85045","order_by":3,"name":"Xin Xu","email":"","orcid":"","institution":"Children’s Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Xu","suffix":""},{"id":443733209,"identity":"d236e0ae-9e72-4b2b-ae70-1e5ced4d753c","order_by":4,"name":"Caihong Fu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYBAC+wNAIrEBxGRsYPgApAwIaQErgGlhnAETOUBIC2MDhMPMQ5QWieSHHx7usMmTj0hue2zbZiNvzsB78PEHPFrsJdKMJRLPpBUb3khsN85tSzPc2cCXbIDflhwGicS2w4kbew62See2HWbccIDHTIKAFuYfcC2Wbf/tgVrMfxDQwga2ZT57Y5s0Y9uBRJAt+L3P88zMIrEtLXEDe2O7Yc+55OQNh3mMJc7g08Ke/PjmzzabxPnN7M8e/Cizs91wvMfwQwUeLQi9BxjYGBjZgCxmYpSDgHwDUAvDH2KVj4JRMApGwUgCAMTpVD3FwA3iAAAAAElFTkSuQmCC","orcid":"","institution":"Children’s Hospital of Nanjing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Caihong","middleName":"","lastName":"Fu","suffix":""}],"badges":[],"createdAt":"2025-03-18 03:08:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6248851/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6248851/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-025-05788-1","type":"published","date":"2025-06-07T15:57:49+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81016836,"identity":"a79b2166-f2c3-41a5-ab77-8a96d002d9a8","added_by":"auto","created_at":"2025-04-21 09:07:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":136217,"visible":true,"origin":"","legend":"\u003cp\u003eThe flow diagram of the study cohort. ALL=acute lymphoblastic leukemia.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6248851/v1/0e8880971e52f9dd49c7a096.png"},{"id":81016835,"identity":"b82a3a26-3aa5-4a4d-988b-2b087734e57a","added_by":"auto","created_at":"2025-04-21 09:07:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":27545,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curves without ALL-related events that required acute care during long-term follow-up, defining as ALL-related emergency visits, readmitted hospitalizations and occurrence of severe infections for pediatric patients who received routine nutritional screening during hospitalization compared to the matched control cohort without screening during the long-term follow-up. The mean of EFS was significantly longer in screening cohort than control cohort (log-rank test: p\u0026lt;0.001). EFS=event-free-survival.\u003c/p\u003e","description":"","filename":"revisedfigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6248851/v1/d9be347f1155d18516d85c7e.png"},{"id":81016476,"identity":"2d116c3f-3191-4ba3-8877-cea6828b3a83","added_by":"auto","created_at":"2025-04-21 08:59:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":37457,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in health-related QoL from baseline to 24-month follow-up. (a) the mean of EQ--5D-5L utility scores was significantly lower in the combined screening group as opposed to the control group using basic screening tool at 3-, 6-, 12-and 24- month follow-up; and (b) the mean of QALYs calculated by area under the curve in the combined screening group was significantly lower than that in control group across all time points during the 24 months follow-up. QoL=quality of life; QALYs=quality-adjusted life year. *p\u0026lt;0.05.\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6248851/v1/f166a55cf1c436af2652d541.png"},{"id":84243158,"identity":"706be426-8433-4dac-93d7-73cb12422c60","added_by":"auto","created_at":"2025-06-09 16:12:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":643444,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6248851/v1/4ed726d1-a099-426c-b89d-73ccb2211a12.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of Nutritional Screening in Children with Acute Lymphoblastic Leukemia Undergoing the Maintenance Chemotherapy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in child, accounting for the world age-standardized incidence of 46.4 per million per year in children aged 0\u0026ndash;14 years and 28.5 per million in adolescents aged 15\u0026ndash;19 years\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. The cancer registration data show the same trend in China\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Chemotherapy remains the standard treatment for pediatric ALL, which usually has three phases-induction, consolidation and maintenance over the course of several years, with the 5-year survival rate can be over 80%\u003csup\u003e3, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. However, the severity of post-treatment myelosuppression increases as the frequency and intensity of chemotherapy rise, leading to the vulnerability of malnutrition. Adverse reactions to aggressive chemotherapy drugs and emotional instability also result in a diminished appetite in patients\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. In addition, corticosteroids, integral component of ALL maintenance treatment are also likely contributors to impact children\u0026rsquo;s ability to take normal diet, thus contributing to a further decrease in nutritional status during the final and longest maintenance treatment stage\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. In turn, patients with nutritional deficiencies have impaired haemopoietic and immune functions\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. These evidences suggest that under-nutrition have been emphasized to be closely correlated with clinical efficacy, chemotherapy tolerance and prognosis in cases of ALL\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Furthermore, malnutrition decreases quality of life and prolongs length of hospital stay\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. It is well known that the European Society for Clinical Nutrition and Metabolism (ESPEN) expert group emphasized the screen cancer patients for nutritional risk early in the course of their care\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Although malnutrition risk at the induction or intensification chemotherapy was significantly higher in patients who were not in remission than in the patients at any time during the maintenance therapy, previous research emphasized longitudinal changes of nutritional status in childhood cancer is a dynamic process, therefore, clinicians should follow up closely with re-evaluation required at each phase of treatment, among which maintenance is the last phase, indicating to prevent relapse of the disease and lasting for around 2\u0026ndash;3 years\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Previous studies addressing this aspect from different parts of world has been reported, whereas, there is a lack in Chinese children with ALL, which might due to the absence of a gold standard measure\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Recently, the Subjective Global Nutritional Assessment (SGNA) represented a simple, comprehensive, organized and non-invasive, tool in pediatric patients, which has been proved to be highly sensitive tool for assessing nutritional status and identify children at risk of developing malnutrition with good inter-observer reliability and for prediction of post-operative adverse events\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDue to the limited evidences regarding its clinical use, the study aimed to evaluate the effectiveness of implementing the routine nutritional screen to identify \u0026ldquo;at risk\u0026rdquo; nutritional status in children diagnosed with ALL on maintenance therapy, that followed by a referral to the specialists in the nutrition department of our hospital for early nutritional intervention, to influence the event-free survival (EFS) and quality-adjusted life years (QALYs) during long-term follow-up.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participant selection\u003c/h2\u003e \u003cp\u003eThe institutional Ethics Examining Committee of Human Research (TZRMH-2025KY-008) authorized ethical approval for a retrospective propensity score-matched cohort study in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines based on the principles of the Declaration of Helsinki\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Informed consents were waived for adult patients, because all data were retrieved from the existing medical and administrative records to inform treatment. No patients were contacted for the study and no personal data were disclosed. Whereas, informed consents were obtained from the parents or legal guardians for participants younger than the age of 16 after enrollment.\u003c/p\u003e \u003cp\u003eBetween January 1, 2020 and February 28, 2024, the reviews of pediatric patients who admitted to our hospital for the treatment of ALL according to the South China Children\u0026rsquo;s Leukemia Group-ALL-2015 protocol were extracted from the electronic medical records (EMRs)\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Inclusion criteria were as follows: ⑴ confirmed diagnosis of ALL by the criteria from the 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukmia\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e; ⑵ aged 0 to 18 years of age at diagnosis; ⑶ on maintenance chemotherapy using 6-mercaptopurine 50mg/m\u003csup\u003e2\u003c/sup\u003e every day and methotrexate 25 mg/m\u003csup\u003e2\u003c/sup\u003e one day per week according to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (version 2.2021)\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Patients were excluded due to Philadelphia chromosome\u0026ndash;positive ALL, relapsed/refractory disease, down syndrome, pulmonary/bone metastasis, neuromuscular disease, severe metabolic disease or gastrointestinal disease; hepatic or renal dysfunction and incomplete data.\u003c/p\u003e \u003cp\u003eThe review of 515 consecutive patients who were identified as the screening cohort were retrospectively retrieved from the electronic medical records (EMRs). We performed a propensity-score matching analysis of patients, who did not receive nutritional screening over the same period, in a 1:1 ratio as control cohort. The score was estimated using the baseline variables by the nearest-neighbor method with a caliper of 0.20: ⑴ age; ⑵ gender; ⑶ ALL immunophenotype; ⑷ Karyotye analysis; ⑸ white blood cell (WBC) count at diagnosis; ⑹ ALL risk category based on the International Berlin-Frankfurt-Munster Group Study Group and IntReALL Consortium risk classification\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e; ⑺ end of induction-measurable residual disease (EOI-MRD); ⑻ post-induction condition; ⑼ extramedullary disease; ⑽ central nervous system leukemia (CNSL); ⑾ prednisone response; ⑿ serum albumin and body mass index (BMI) on the first day of admission.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eNutritional screening\u003c/h3\u003e\n\u003cp\u003eGiven that nutritional screening was not a routine procedure, the patients were engaged to selecting the management option most closely aligned with his/her values and preferences. Within 48 hours upon admission, patients were screened for nutritional risk using SGNA questionnaire, which has been widely used for more than 20 years to screen the nutritional status for pediatric patients, who are hospitalized, with neurocognitive disabilities or chronic illness/disease. The screening was performed by specially trained nurse staff at each cycle of maintenance for patients with agreement. Cases with a positive screening result were prescribed to a dietitian for detailed assessment to produce an early nutritional intervention or support.\u003c/p\u003e\n\u003ch3\u003eOutcomes measurement\u003c/h3\u003e\n\u003cp\u003eThe SGNA nutrition-screening tool uses both subjective and objective nutrition-focused aspects to identify nutritional status, considering seven specific features of medical history (height-for-age, weight-for-height, changes in body weight, adequacy of dietary intake, gastrointestinal symptoms, functional capacity, and metabolic stress of disease) and three parameters of physical examination (loss of subcutaneous fat, muscle wasting, and edema) for signs of inadequate energy and/or protein intake. A child\u0026rsquo;s nutritional status is categorized in accordance with the SGNA rating form as ⑴ normal/well nourished: The patient is growing and gaining weight normally, has a grossly adequate intake without gastrointestinal symptoms, shows no or few physical signs of wasting, and exhibits normal functional capacity. Normal ratings in most or all categories, or significant, sustained improvement from a questionable or moderately malnourished state. It is possible to rate a patient as well-nourished in spite of some reductions in muscle mass, fat stores, weight and intake. This is based on recent improvement in signs that are mild and inconsistent. ⑵ moderately malnourished: This patient has definite signs of a decrease in weight and/or growth, and intake and may or may not have signs of diminished fat stores, muscle mass and functional capacity. This patient is experiencing a downward trend, but started with normal nutritional status. Moderate ratings in most or all categories, with the potential to progress to a severely malnourished state. ⑶ severely malnourished: This patient has progressive malnutrition with a downward trend in most or all categories. There are significant physical signs of malnutrition\u0026mdash;loss of fat stores, muscle wasting, weight loss \u0026gt;10%\u0026mdash;as well as decreased intake, excessive gastrointestinal losses and/or acute metabolic stress, and definite loss of functional capacity. Severe ratings in most or all categories with little or no sign of improvement\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. The levels of serum albumin (ALB), prealbumin (PA) and retinol binding protein (RBP) were measured from fasting blood specimens. The levels of T-cell subsets in peripheral blood were detected by immunofluorescence and flow cytometry to calculate the percentage of natural killer (NK) cells as immune indicators. Length of hospital stay (LOS) was predefined as days from admission to discharge from the ward, and prolonged LOS was considered as LOS\u0026gt;8 days. Early readmission was defined as readmission to hospital within 30 days post-discharge due to all-cause. The health-related quality of life (HR-QoL) was evaluated using the QALYs, which were calculated using the European quality of life five-dimensional (EQ-5D-5L) utility values over time following the area under the curve (AUC) method. The EQ-5D-5L questionnaire contained five domains: mobility, self-care, usual activity, pain or discomfort and anxiety or depression. Each dimension is scored using a 5-points likert scale, depending on whether the respondent has no, slight, moderate, severe or extreme problems. Utility scores were calculated by the Euro-QoL crosswalk set of utility index values to their EQ-5D-SL health states. The QALYs were generated via the AUC when the utility scores were plotted over time\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eData on demographic and other clinical data were retrieved from EMRs, SGNA scores and QALYs scores were extracted from medical database, which were collected through telephone interview by specially trained nurses according to our clinical protocol. The primary endpoint was the long-term survival without events that required acute care during long-term follow-up, defining as ALL-related emergency visits, readmitted hospitalizations and occurrence of severe infections.\u003c/p\u003e\n\u003ch3\u003eSample size calculation\u003c/h3\u003e\n\u003cp\u003ePASS statistical software, version 22.0 (NCSS, LLC. Kaysville, Utah, USA) was used for sample size calculation. Based on a multidisciplinary experts\u0026rsquo; consensus from a series of cases discussion, an equal sample allocation superiority was designed to compare the hazard rates of ALL-pediatric patients receiving a routine nutritional screening to those without screening using a log-rank test. The hazard rate was supposed to be 2.0, we wanted to show that it decreased by at least 25% when the nutritional screening was performed, which was considered to be clinically better for EFS of ALL\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. We wanted to compare sample size when the power was 0.80 with two-side type I error of 5%, and the difference in hazard rates was between \u0026minus;\u0026thinsp;0.8 and \u0026minus;\u0026thinsp;0.3, specifying the value of the clinical superiority margin by 0.5. If the data-loss rate was estimated to be 20% in both two cohorts, the sample size was 587 cases in either screening or control cohort.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eSPSS software version 22.0 (SPSS Inc, Chicago, IL) was used for statistics analysis. Significant level was reported as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Data normality was performed using Kolmogorov-Smirnov Z test. Nominal distributed data, non-normally distributed data and categorical data were recorded as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), median\u0026thinsp;\u0026plusmn;\u0026thinsp;inter quartile range (IQR) and percentage. Differences between groups were compared using the student t test, Mann-Whitney U test and Chi-squared test. The probability of EFS was evaluated by the Kaplan-Meier method, and differences among cohorts were assessed by log-rank analysis with 95% confidence interval (CI). The censored point was defined as disease-free survival at the last follow-up assessment.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e showed the cohort flow diagram, a total of 1174 pediatric patients with ALL were identified for this study cohort. After propensity score matching, the screening cohort included 515 cases and 523 in the matched cohort. Table\u0026nbsp;1 showed the demographic and clinical characteristic of patients at baseline, which were well balanced between the two study cohorts.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA total of 74.2%, 19.4% and 6.4% of cases in the screening cohort were respectively categorized as being at normal/well, moderately and severely malnourished during their maintenance treatment based on the SGNA nutritional screening tool for malnutrition risk. Occurrence of hypoproteinemia was reported in 11.1% and 31.5% cases in screening and control cohort at 4 weeks post-discharge, with significant between-group differences (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In addition, 23.1% of patients in screening cohort had a prolonged LOS \u0026gt;8 days, compared with 40.1% of cases in control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). As shown in table 2, the levels of ALB, PA and RBP were significantly higher in screening cohort at 4 weeks after the last maintenance cycle (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while the lower in screening cohort as compared to the matched cohort at 4-week post-discharge following the last maintenance cycle (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eThere were 26.8% of patients in screening cohort reporting ALL-related events requiring acute care as compared to 46.5% of cases in control cohort (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) according to the Kaplan-Meier curves showed in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Specifically, there were significantly lower proportion of patients in screening cohort in ALL-related emergency room visits (7.0% vs. 24.3%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), re-hospitalization (13.2% vs. 28.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and severe infection (6.6% vs. 13.6%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) as opposed to those in control cohort during the long-term follow-up. Superiority was met, as the hazard ratio of the primary outcome was 0.397, the 95% confidence interval of 0.306 to 0.493 which felt within the predefined superiority margin of 0.5. As a matter of fact, the mean of long-term EFS was significantly longer in patients receiving nutritional screening than those as controls (24.07 (95%CI: 23.09, 25.04) vs. 18.02 (95%CI: 16.62, 19.42), log-rank p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e illustrated the quality of life between the two groups using the EQ-5D-5L utility and the corresponding QALYs over the long-term follow-up. There was a trend to reduction in the mean of QALYs for patients in both two groups. However, the means of QALYs calculated by AUC up to 3 (20.94\u0026thinsp;\u0026plusmn;\u0026thinsp;12.64 vs. 17.33\u0026thinsp;\u0026plusmn;\u0026thinsp;3.18, p\u0026thinsp;=\u0026thinsp;0.039), 6 (29.12\u0026thinsp;\u0026plusmn;\u0026thinsp;13.64 vs. 17.91\u0026thinsp;\u0026plusmn;\u0026thinsp;3.86, p\u0026thinsp;=\u0026thinsp;0.016), 12 (34.95\u0026thinsp;\u0026plusmn;\u0026thinsp;15.59 vs. 20.45\u0026thinsp;\u0026plusmn;\u0026thinsp;4.05, p\u0026thinsp;=\u0026thinsp;0.009) and 24 months (39.12\u0026thinsp;\u0026plusmn;\u0026thinsp;16.17 vs. 21.03\u0026thinsp;\u0026plusmn;\u0026thinsp;14.36, p\u0026thinsp;=\u0026thinsp;0.001) after discharge were significantly lower in the combined screening group as opposed to the matched control group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study firstly examined the long-term consequence of post-discharge EFS in relation to an implementation of routine nutritional screening for pediatric patients with ALL undergoing the maintenance chemotherapy. Our findings confirmed that the long-term EFS rate had been significantly improved in screening cohort, the average gain in immunocompetence and QALYs was higher for patients receiving nutritional screening as compared to matching control cohort, which might attribute to accurate assessment of nutritional status for early intervention of pediatric patients.\u003c/p\u003e \u003cp\u003eEvidences revealed that the composition of pediatric body composition including bone density, fat- and fat-free mass and total body water, are changed primarily by caner itself, aggressive multimodal treatments, metabolism changes, unbalanced diet and physical activity reduction, influencing the patient\u0026rsquo;s nutritional status\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. In turn, nutritional status disorders can modify the metabolism, volume distribution and clearance of chemotherapy, then change the drug pharmacokinetics to impair the effectiveness of cancer treatment and alter the cytokine hormone function to decrease the ability of immune response against infection\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Malnutrition adversely affects several clinical outcomes in terms of disease progression, survival, treatment-related morbidity and risk of infection. Likewise, it has been proved to be associated with a poor health-related quality of life\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. The proportion of nutritional status disorders with pediatric ALLs at diagnosis ranges from 6\u0026ndash;21.2%, and increased to 52.6% after at least one chemotherapy cycle\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. As result, a systematic and standard approach of screening for nutritional status with adequate tool should be offered to all pediatric patients with ALL, which could be intervened upon to improve their clinical outcomes.\u003c/p\u003e \u003cp\u003eIn the present study, we employed a validated method for the overall pediatric population to identify the nutritional risk among the study population, which was not taken as a routinely reported practice up to now. Of the 515 cases in screening cohort, normal nutrition were reported in 74.2% of cases, moderate malnutrition in 19.4% and severe malnutrition in 6.4%, which was consistent with the previous reported median prevalence of undernutrition ranging from 10.3\u0026ndash;20% at last maintenance cycle\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Although meeting the nutritional requirements in these pediatric cancer population is challenging, the enteral or parenteral nutritional support is frequently used to effectively reverse malnutrition associated with the anti-neoplastic treatment, promote treatment tolerance and improve immune function\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Yueqin Han et al estimated the application of nutrition therapy in childhood ALL during chemotherapy, their results showed the concentrations of ALB were significantly increased, while the percentages of CD3+, CD4+, CD4+/CD8+, NK cell significantly decreased at 4 weeks post-treatment\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. In this study, we also found a significantly better improvement of immune function in screening cohort than control cohort. In contrast, patients with a malnourished status assessed by the SGNA were 1.95-time (95%CI: 1.12, 3.39) more likely to be readmitted as opposed to the well-nourished (p\u0026thinsp;=\u0026thinsp;0.017)\u003csup\u003e30\u003c/sup\u003e. Moreover, malnourished ALL-children had 2 to 3 times prone to suffer from infection compared to well nourished (p\u0026thinsp;=\u0026thinsp;0.024), and thus prolonged the duration of treatment, hospital stay, even could lead to death\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Consistent with previous evidences, our Kaplan-Meier survival analysis in screening cohort indicated a significantly greater outcome of the long-term probability of EFS than those did not receive screening for malnutrition risk in control cohort, which were in line with a meta-analysis concluding that malnutrition was associated with poorer overall survival (RR\u0026thinsp;=\u0026thinsp;1.36 (95%CI: 1.16, 1.60) and EFS (RR\u0026thinsp;=\u0026thinsp;1.56 (95%CI:1.32, 1.86)), respectively, supporting the essential to recognize and achieve optimal nutritional status by nutrition intervention to improve treatment results in pediatric ALL\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn addition, the implementation of a routine nutritional screening had a significantly markable impact on QoL over 24 months with a greater QALY score as opposed to control cohort without screening, which indicated that the routine nutritional screening was a useful process to distinguish the risk of malnutrition for pediatric patients with ALL, and minimized the delay in referral to a dietitian for early diagnosis and intervention to achieve a better nutritional status, therefore, further improved HR-QoL over time. Similarly, previous reviews showed nutritional assessment and early intervention in pediatric patients with caners could significantly improve their HR-QoL\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, it was a single-center design, which limited its generalizability to all hospitalized pediatric ALLs. Second, investigators responsible for outcome assessment were not blinded due to the nature of retrospective study, which might yield confounding bias. Third, although our hospital the largest tertiary center in the city, we did not capture all readmissions for cases in our cohort, because patients were likely to be readmitted in other medical centers. Four, we did not measure the micronutrients in both the cohorts. In the future, there is a need for a well-designed, randomized, controlled study to verify our results.\u003c/p\u003e \u003cp\u003eIn conclusion, the implementation of routine nutritional screening in pediatric ALL patients could significantly improve the long-term ESF, when defining ALL-related events as ALL-related emergency visits, readmitted hospitalizations and occurrence of severe infections, and accounted for a significant improvement in scores of QALY over long-term follow-up.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacute lymphoblastic leukemia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEFS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eevent-free-survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eQALYs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003equality-adjusted life years\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSGNA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSubjective Global Nutritional Assessment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEMRs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eelectronic medical records\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEOI-MRD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einduction-measurable residual disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHR-QoL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehealth-related quality of life\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEQ-5D-5L\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean quality of life five-dimensional\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elength of hospital stay\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAUC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eunder the curve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003estandard deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einter quartile range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence interval.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthic approval and consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ethic was approved by the institutional Ethics Examining Committee of Human Research (TZRMH-KY-2025015) based on the principles of the Declaration of Helsinki. Informed consents were waived for adult patients, because all data were retrieved from the existing medical and administrative records to inform treatment. No patients were contacted for the study and no personal data were disclosed. Whereas, informed consents were obtained from the parents or legal guardians for participants younger than the age of 16 after enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable。\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCaihong Fu was involved in the conception and design, analysis and interpretation of the data; the drafting of the paper, revising it critically for intellectual content; and the final approval of the version to be published.\u003c/p\u003e\n\u003cp\u003eXin Xu was involved in the conception and design, analysis and interpretation of the data; the drafting of the paper, revising it critically for intellectual content; and the final approval of the version to be published.\u003c/p\u003e\n\u003cp\u003eXuefen Zhao was involved in the conception and design, analysis and interpretation of the data; the drafting of the paper, revising it critically for intellectual content.\u003c/p\u003e\n\u003cp\u003eJuan Wang was involved in the conception and design; the drafting of the paper, revising it critically for intellectual content.\u003c/p\u003e\n\u003cp\u003eLi Chen was involved in the conception and design; the drafting of the paper, revising it critically for intellectual content.\u003c/p\u003e\n\u003cp\u003eAnd all authors agreed to be accountable for all aspects of the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSteliarova-Foucher E, Colombet M, Ries L, Moreno F, Dolya A, Bray F, et al. International incidence of childhood cancer, 2001-10: a population-based registry study. LANCET ONCOL. 2017;18:719\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZheng R, Peng X, Zeng H, Zhang S, Chen T, Wang H, et al. Incidence, mortality and survival of childhood cancer in China during 2000\u0026ndash;2010 period: A population-based study. CANCER LETT. 2015;363:176\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCooper SL, Brown PA. Treatment of pediatric acute lymphoblastic leukemia. PEDIATR CLIN N AM. 2015;62:61\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaynon PS, Angiolillo AL, Carroll WL, Nachman JB, Trigg ME, Sather HN, et al. Long-term results of the children's cancer group studies for childhood acute lymphoblastic leukemia 1983\u0026ndash;2002: a Children's Oncology Group Report. Leukemia. 2010;24:285\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiamantaras AA, Dessypris N, Sergentanis TN, Ntouvelis E, Athanasiadou-Piperopoulou F, Baka M, et al. Nutrition in early life and risk of childhood leukemia: a case-control study in Greece. CANCER CAUSE CONTROL. 2013;24:117\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTouyz LM, Cohen J, Neville KA, Wakefield CE, Garnett SP, Mallitt KA et al. Changes in body mass index in long-term survivors of childhood acute lymphoblastic leukemia treated without cranial radiation and with reduced glucocorticoid therapy. PEDIATR BLOOD CANCER. 2017;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChandra RK. Immunocompetence in undernutrition. J PEDIATR-US. 1972;81:1194\u0026ndash;200.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLobato ME, Ruiz-Arguelles GJ. Leukemia and malnutrition. III. Effect of chemotherapeutic treatment on the nutritional state and its repercussion on the therapeutic response of patients with acute lymphoblastic leukemia with standard risk]. Sangre (Barc). 1990;35:189\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrinksma A, Huizinga G, Sulkers E, Kamps W, Roodbol P, Tissing W. Malnutrition in childhood cancer patients: a review on its prevalence and possible causes. CRIT REV ONCOL HEMAT. 2012;83:249\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEspinoza M, Perelli J, Olmos R, Bertin P, Jara V, Ramirez P. Nutritional assessment as predictor of complications after hematopoietic stem cell transplantation. Rev Bras Hematol Hemoter. 2016;38:7\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArends J, Baracos V, Bertz H, Bozzetti F, Calder PC, Deutz N, et al. ESPEN expert group recommendations for action against cancer-related malnutrition. CLIN NUTR. 2017;36:1187\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGonzalez A, Cortina L, Gonzalez P, Gonzalez C, Garcia T, de Svarch EG. Longitudinal assessment of nutritional status in children treated for acute lymphoblastic leukaemia in Cuba. EUR J CANCER. 2004;40:1031\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJaime-Perez JC, Gonzalez-Llano O, Herrera-Garza JL, Gutierrez-Aguirre H, Vazquez-Garza E, Gomez-Almaguer D. Assessment of nutritional status in children with acute lymphoblastic leukemia in Northern Mexico: A 5-year experience. PEDIATR BLOOD CANCER. 2008;50:506\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarter L, Hulst JM, Afzal N, Jeejeebhoy K, Brunet-Wood K. Update to the pediatric Subjective Global Nutritional Assessment (SGNA). NUTR CLIN PRACT. 2022;37:1448\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evon Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. INT J SURG. 2014;12:1495\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChu J, Cai H, Cai J, Bian X, Cheng Y, Guan X, et al. Prognostic significance of steroid response in pediatric acute lymphoblastic leukemia: The CCCG-ALL-2015 study. FRONT ONCOL. 2022;12:1062065.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown PA, Shah B, Advani A, Aoun P, Boyer MW, Burke PW, et al. Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J NATL COMPR CANC NE. 2021;19:1079\u0026ndash;109.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLocatelli F, Schrappe M, Bernardo ME, Rutella S. How I treat relapsed childhood acute lymphoblastic leukemia. Blood. 2012;120:2807\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSecker DJ, Jeejeebhoy KN. How to perform Subjective Global Nutritional assessment in children. J ACAD NUTR DIET. 2012;112:424\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Hout B, Janssen MF, Feng YS, Kohlmann T, Busschbach J, Golicki D, et al. Interim scoring for the EQ-5D-5L: mapping the EQ-5D-5L to EQ-5D-3L value sets. VALUE HEALTH. 2012;15:708\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuzman-Leon AE, Gallegos-Castorena S, Romo-Rubio H, Casillas-Toral E, Lopez-Teros V, Stein K. Nutritional status at diagnosis and its relationship with survival and relapse in Mexican children with acute lymphoblastic leukemia: a retrospective study. BMC Cancer. 2025;25:325.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchab M, Skoczen S. Nutritional status, body composition and diet quality in children with cancer. FRONT ONCOL. 2024;14:1389657.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchoon S, Makamo N, Uittenboogaard A, Bernhardt MB, Ozuah NW, Kaspers G et al. Impact of undernutrition on the pharmacokinetics of chemotherapy in children with cancer: A systematic review. PEDIATR BLOOD CANCER. 2023:e30531.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePedretti L, Massa S, Leardini D, Muratore E, Rahman S, Pession A et al. Role of Nutrition in Pediatric Patients with Cancer. NUTRIENTS. 2023;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eViani K, Albuquerque L, Barr RD, Ladas EJ. Nutrition of Children With Cancer in Brazil: A Systematic Review. JCO GLOB ONCOL. 2020;6:242\u0026ndash;59.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIniesta RR, Paciarotti I, Brougham MF, McKenzie JM, Wilson DC. Effects of pediatric cancer and its treatment on nutritional status: a systematic review. NUTR REV. 2015;73:276\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuzman-Leon AE, Avila-Prado J, Bracamontes-Picos LR, Haby MM, Stein K, Astiazaran-Garcia H, et al. Nutritional interventions in children with acute lymphoblastic leukemia undergoing antineoplastic treatment: a systematic review. BMC NUTR. 2024;10:89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHan Y, Zhang F, Wang J, Zhu Y, Dai J, Bu Y, et al. Application of Glutamine-enriched nutrition therapy in childhood acute lymphoblastic leukemia. NUTR J. 2016;15:65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLetourneau J, Belanger V, Marchand V, Boctor DL, Rashid M, Avinashi V, et al. Post-discharge complications and hospital readmissions are associated with nutritional risk and malnutrition status in a cohort of Canadian pediatric patients. BMC PEDIATR. 2024;24:469.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHafiz MG, Mannan MA. Nutritional status at initial presentation in childhood acute lymphoblastic leukemia and its effect on induction of remission. Mymensingh Med J. 2008;17:S46\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiakatou V, Vassilakou T. Nutritional Status of Pediatric Cancer Patients at Diagnosis and Correlations with Treatment, Clinical Outcome and the Long-Term Growth and Health of Survivors. CHILDREN-BASEL. 2020;7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"acute lymphoblastic leukemia, nutritional screening, event-free-survival, readmission, infection, quality-adjusted life years","lastPublishedDoi":"10.21203/rs.3.rs-6248851/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6248851/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e To investigate the effectiveness of the routine nutritional screening for malnutrition risk in hospitalized children with acute lymphoblastic leukemia (ALL) on maintenance chemotherapy from the viewpoint of clinical outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e The reviews of 1038 pediatric patients were retrieved for the retrospective, propensity score-matched, superiority study. A 1:1 propensity score matching was utilized to match patients who received nutritional screening (screening cohort) to those who remained usual care without screening (control cohort). The primary endpoint was the long-term event-free-survival(EFS) after the last cycle of maintenance. Secondary outcomes included immune function, complications and long-term quality-adjusted life years (QALYs).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The proportion of cases with risk of malnutrition in screening was 25.8%. At the end of 4 weeks following the last cycle, the level of serum albumin was higher in screening cohort than control cohort (p\u0026lt;0.001), while the cellular immune function significantly improved in screening cohort (all p\u0026lt;0.05). During a mean of 11.09±6.45 months follow-up, 28.6% of patients in screening cohort had an event including ALL-related emergency visits, readmitted hospitalizations and severe infections compared to 46.5% of cases in control cohort yielding a hazard ratio of 0.397 (95%CI: 0.306, 0.493 and a significant difference in long-term EFS (24.07 (95%CI: 23.09, 25.04) vs. 18.02 (95%CI: 16.62, 19.42), log-rank p\u0026lt;0.001). The means of QALYs calculated by area under the curve up to 3, 6, 12 and 24 months after discharge were significantly lower in screening cohort as opposed to control cohort (all p\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Pediatric ALL receiving the specific-for-children nutritional screening during hospitalization exhibited a better EFS over the 24-month follow-up than cases without screening. The benefit accounted for a significant improvement in immune function and QALYs scores over long-term follow-up.\u003c/p\u003e","manuscriptTitle":"Effect of Nutritional Screening in Children with Acute Lymphoblastic Leukemia Undergoing the Maintenance Chemotherapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-21 08:59:37","doi":"10.21203/rs.3.rs-6248851/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-21T07:54:39+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-19T07:38:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-16T09:10:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"129194223626812537461556879219377579961","date":"2025-04-15T07:28:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"275168320340638150871198446403571861501","date":"2025-04-13T07:35:44+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-13T07:11:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-12T15:02:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2025-04-09T04:34:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"461d0e41-fc01-4ca4-aff9-eb2dd323aae5","owner":[],"postedDate":"April 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-09T16:10:40+00:00","versionOfRecord":{"articleIdentity":"rs-6248851","link":"https://doi.org/10.1186/s12887-025-05788-1","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2025-06-07 15:57:49","publishedOnDateReadable":"June 7th, 2025"},"versionCreatedAt":"2025-04-21 08:59:37","video":"","vorDoi":"10.1186/s12887-025-05788-1","vorDoiUrl":"https://doi.org/10.1186/s12887-025-05788-1","workflowStages":[]},"version":"v1","identity":"rs-6248851","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6248851","identity":"rs-6248851","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}