Prevalence and risk factors of chemotherapy-induced oral mucositis in 470 children with acute lymphoblastic leukemia

Prevalence and risk factors of chemotherapy-induced oral mucositis in 470 children with acute lymphoblastic leukemia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prevalence and risk factors of chemotherapy-induced oral mucositis in 470 children with acute lymphoblastic leukemia Xiaofeng He, Weijie Wang, Lichan Liang, Xiaomei Liao, Jiayin Huang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4256541/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: To comprehensively assess the prevalence and risk factors of chemotherapy-induced oral mucositis in 470 children diagnosed with acute lymphoblastic leukemia in China, and to gain a better understanding of the treatment-related risk factors. Methods: In this retrospective study, 470 children diagnosed with acute lymphoblastic leukemia in China between January 2020 and July 2022 were included. Data on sociodemographic characteristics, nutritional status, disease and treatment history, blood biochemistry, and microbiological factors were gathered using electronic medical records, alongside oral and dietary information collected through field investigations and telephone follow-ups. The association between chemotherapy-induced oral mucositis and these variables was assessed using univariate and multivariate logistic analyses. Results: The study found a high prevalence (45.1%) of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia. The occurrence of oral mucositis was associated with several factors, including receiving more than five chemotherapy cycles ( P <0.001), carrying HSV-1( P =0.016), being infected with Candida albicans( P =0.012), undergoing chemotherapy with specific drugs containing methotrexate/daunorubicin/cytarabine( P <0.001), having a high clinical risk stratification( P =0.002), and being over 6 years old( P =0.002). Conclusion: The study suggests that the prevalence of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia is relatively high. It emphasizes the importance of clinical medical staff paying attention to this issue and adopting targeted interventions to reduce the prevalence of oral mucositis in this patient population. Acute lymphoblastic leukemia Chemotherapy Oral mucositis Risk factor Introduction Malignant tumors have been the second reason for death in children[ 1 ]. In China, more than 120, 000 children and adolescents aged 0 to 19 years were diagnosed with cancer between 2018 and 2020, and on average, more than 40, 000 children were newly diagnosed with cancer each year[ 2 ]. According to statistics, the incidence of childhood cancer has been increasing by 2.8% per year for nearly a decade[ 2 ]. Acute lymphoblastic leukemia is one of the most common types of childhood cancer and childhood leukemia, accounting for 26% of cancer cases in children aged 0 to 14[ 3 ], 55.82% of leukemia cases in children and adolescents aged 0 to 19 years and approximately 75% of newly diagnosed leukemia[ 2 ]. As treatment technology is being constantly improved, the 5-year survival rate for patients with acute lymphoblastic leukemia has increased from 57–90%[ 3 ]. At present, the focus has now shifted towards achieving early remission and addressing long-term complications of the disease[ 4 ]. The emphasis on chemotherapy as the main treatment also highlights the need to address its associated complications, such as oral mucositis as mentioned earlier[ 5 ]. In comparison to adult cancer patients, pediatric cancer patients are more susceptible to developing oral mucositis[ 6 ]. The incidence of oral mucositis among pediatric cancer patients ranges from 33–80%[ 6 ]. Furthermore, after high-dose methotrexate chemotherapy, the incidence of oral mucositis in these patients can reach 74.9%[ 7 ]. Moreover, the incidence of oral mucositis in children with hematologic tumors is significantly higher, ranging from 7.0 to 7.1 times than those of children with other tumors[ 7 ]. This warrants particular attention given that acute lymphoblastic leukemia is the most prevalent hematologic tumor in children[ 3 ]. The clinical symptoms of oral mucositis encompass atrophy, redness, ulceration, and bleeding accompanied by pain, which can lead to secondary infection or systemic infection, disruption of chemotherapy, prolonged hospital stays, and malnutrition[ 8 ]. Additionally, oral mucositis imposes a significant psychological burden on patients, often being regarded as the most undesirable event during chemotherapy treatment[ 9 ]. This emotional impact may lead to negative emotions in patients and influence treatment quality and patient compliance[ 10 , 11 ]. Substantial advancements have been achieved in comprehending the pathobiology of oral mucositis. Oral mucositis does not simply result from epithelial cell injury; rather, its mechanism comprises five stages: initiation, signal transmission, amplification, ulceration, and healing[ 12 ]. The pathogenesis of oral mucositis is complex, and currently, none of the preventive measures are effective in addressing the entire process[ 13 ]. Identifying the risk factors associated with chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia is crucial for developing effective, targeted interventions to prevent or delay its onset and development. The relevant risk factors of oral mucositis in children with acute lymphoblastic leukemia have been described in the existing literature. We carried out a systematic review to understand the risk factors of oral mucositis in children with acute lymphoblastic leukemia[ 14 ]. Factors related to oral mucositis mainly include patient-related factors and treatment-related factors[ 8 ]. However, the treatment-related risk factors of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia remain poorly understood. For example, the majority of relevant studies solely focus on the relationship between the chemotherapy drug methotrexate and oral mucositis in children with acute lymphoblastic leukemia, but there is a lack of studies investigating the correlation between the development of oral mucositis and other chemotherapeutic agents. Additionally, most studies only focus on one-sided influencing factors. Maiguma et al. [ 15 ]detailed the relationship between high-dose methotrexate therapy and oral mucositis in pediatric acute lymphoblastic leukemia. De Mendonça et al. [ 16 ]indicated that the presence of HSV, mainly HSV-1, and Candida spp. were associated with mucositis severity in pediatric acute lymphoblastic leukemia. Santos et al. [ 17 ]implied that HSV-1 may be a risk factor for aggravating the severity of mucositis. Mendonça et al. [ 18 ]revealed that the presence of HSV, platelet count, neutrophil count, and Candida spp. were associated with increased severity of mucositis in children with acute lymphoblastic leukemia. Murshid et al. [ 19 ]uncovered a strong correlation between practice frequency of oral hygiene practice and dietary habits and the developmental severity of oral mucositis in children with acute lymphoblastic leukemia. Devi et al.[ 20 ] reported the relationship between oral care practice at home and oral mucositis incidence. Figliolia et al.[ 21 ] found the ALL-BFM-95 protocol was associated with the development of oral mucositis in children with acute lymphoblastic leukemia. Gutierrez-Camino et al. [ 22 ]reported that miRNA-4268 rs4674470AA + AG + GG linked to oral mucositis development in children with acute lymphoblastic leukemia. The objective of this study was to comprehensively investigate the prevalence and risk factors of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia in China, and to gain a better understanding of treatment-related risk factors. Methods The retrospective study included 470 children diagnosed with acute lymphoblastic leukemia who received treatment at the pediatric departments of two tertiary hospitals in southern China between January 2020 and July 2022. The study's inclusion criteria were as follows: (a) patients aged 0 to 18 years; (b) diagnosis of acute lymphoblastic leukemia based on the SCCLG-2016 ALL protocol[ 23 ]; (c) absence of oral mucositis before chemotherapy according to the World Health Organization criteria for oral mucositis[ 24 ]; (d) normal communication ability and consent from patients' caregivers; and (e) primary caregivers knowledgeable about patients' oral and dietary condition. Exclusion criteria encompassed patients with other malignant tumors or serious diseases of vital organs. The research obtained approval from the Biomedical Ethics Committee of Southern Medical University ( [2022] No.011) and adhered to the principles of the Declaration of Helsinki. Measures variables A risk factor questionnaire was developed based on a systematic review and the incorporation of clinical expert opinion[ 14 ]. It encompassed the following categories: (a) Sociodemographic data: This included the age of patients at diagnosis, sex, father's level of education, mother's level of education, and monthly household income. (b) Nutritional data: The body mass index for age Z-score ((BMI measured value - data median) / data standard deviation) was utilized to assess the nutritional status of patients. This measure was recommended by the World Health Organization to evaluate body size changes in children. In this study, the most recent body mass index for age Z-score before chemotherapy was used. (c) Disease and chemotherapy data: This category encompassed clinical risk stratification, immune stratification, disease duration, disease location (central or peripheral), treatment stage, recurrence, chemotherapy cycle, and chemotherapy drugs containing MTX/DNR/Ara-C. (d) Blood biochemical data: Parameters included the count of white blood cells at diagnosis, as well as the counts of white blood cells, red blood cells, hemoglobin, platelets, and neutrophils before chemotherapy. The measurements taken one day before chemotherapy were utilized. (e) Microbial data: This section captured whether the patient carried HSV-1 or was infected with Candida albicans during previous or current chemotherapy sessions.(f) Oral and dietary data: Information regarding the frequency of preventive mouthwash before chemotherapy, the number of meals per day during chemotherapy, the main food type per day during chemotherapy, toothbrush type during chemotherapy, and previous history of oral mucositis, dental caries, periodontitis, or gingivitis. The diagnosis of oral mucositis was conducted using the World Health Organization's criteria: grade 0 = no mucositis, grade 1 = erythema without lesions, grade 2 = ulcers, but able to eat, grade 3 = painful ulcers, but able to intake liquid food, grade 4 = unable to eat by mouth. Data collection The researchers collected medical record data of children following standardized training. To obtain oral and dietary data, caregivers who were familiar with the children's conditions were approached. In cases where children had been discharged, researchers utilized field investigations or telephone follow-ups, depending on whether the children were at home or in the hospital, to gather relevant information. Pediatricians documented the onset time and symptoms of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia. In an effort to minimize subjective bias, the severity of oral mucositis was evaluated by uninformed researchers who had undergone uniform training. Data analyses The statistical data were analyzed using IBM SPSS 26.0 software. The Chi-square test was employed to examine the relationship between the occurrence of oral mucositis and quantitative data, including age at diagnosis, sex, and immune classification. An independent t-test was conducted to identify the correlation between the occurrence of oral mucositis and measures of red blood cell count and hemoglobin level. The Wilcoxon test was utilized to analyze the relationship between the occurrence of oral mucositis and other ordinal variables. Variables with a P-value less than 0.05 in the univariate analysis were included in the multivariate logistic regression model for further discussion, and the stepwise backward method was employed to identify independent risk factors. The significance level was set at 0.05. Results Sociodemographic characteristics The sociodemographic characteristics of the children with acute lymphoblastic leukemia are summarized in Table 1. Among the 470 children analyzed, 289 (61.5%) were male and 181 (38.5%) were female. Their ages ranged from 0 to 17 years, with a mean age of 4.00 (3.00 ~ 7.00) years. Among the 470 children, 212 developed chemotherapy-induced oral mucositis, resulting in a prevalence of 45.1%. Of these cases, 138 were classified as grade Ⅰ, 43 as grade Ⅱ, 14 as grade Ⅲ, and 17 as grade Ⅳ. The results of univariate analysis The results of the univariate analysis are summarized in Table 2. Statistically significant differences were observed in various factors, including age, father's level of education, monthly household income, clinical risk classification, immune classification, duration of disease, count of red blood cells, hemoglobin, platelets, and neutrophils before chemotherapy. Additionally, factors such as the presence of central or peripheral disease, treatment stage, chemotherapy cycle, specific chemotherapy drugs, presence of HSV-1, infection with candida albicans, frequency of preventive mouthwash before chemotherapy, and number of meals per day during chemotherapy also showed statistically significant associations ( P < 0.05). The results of multivariate logistic regression analysis Table 3 displays the variable assignment, while Table 4 presents the results of the multivariate logistic regression analysis. Factors influencing the outcome included receiving more than 5 courses of chemotherapy ( OR = 2.631, 95%CI : 1.627–4.255, P < 0.001), HSV-1 infection ( OR = 13.117, 95%CI : 1.601-107.438, P = 0.016), Candida albicans infection ( OR = 6.229, 95%CI : 1.490-26.044, P = 0.012), use of chemotherapy drugs containing MTX/DNR/Ara-C ( OR = 5.972, 95%CI : 2.906–12.272, P < 0.001), high clinical risk stratification ( OR = 0.459, 95%CI : 0.279–0.756, P = 0.002), and being over 6 years old ( OR = 0.499, 95%CI : 0.323–0.772, P = 0.002). Disscusion Oral mucositis is the most common oral complication in children with acute lymphoblastic leukemia[ 25 ]. Factors contributing to oral mucositis mainly encompass patient-related and treatment-related factors[ 8 ]. Yet, the risk factors associated with treatment in children with acute lymphoblastic leukemia have not been comprehensively investigated. This study aimed to explore the incidence and risk factors of chemotherapy-induced oral mucositis in Chinese children with acute lymphoblastic leukemia. Additionally, it sought to offer deeper insights into the treatment-related risk factors. Our findings were consistent with previous studies that have reported a relatively high incidence of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia[ 19 – 21 , 26 ]. This study observed a 45.1% incidence of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia. Figliolia et al.[ 21 ] reported a 46% incidence and Devi et al.[ 20 ] also found a 48.7% incidence of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia. However, our findings demonstrated higher incidences compared to those reported by Murshid et al. [ 19 ]and Azher et al[ 26 ]; Murshid et al.[ 19 ] reported a 23.3% incidence, while Azher et al.[ 26 ] reported a 20.0% incidence. This disparity may be attributed to the fact that the studies by Murshid et al. and Azher et al. only focused on children with acute lymphoblastic leukemia during the induction period. In our study, we observed a notable correlation between age at diagnosis and chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia. Children aged 6 years and above were found to have a lower risk of chemotherapy-induced oral mucositis. These findings contrasted with those of comparable studies, such as Figliolia et al.[ 21 ], Cheng et al.[ 27 ], Fadda et al.[ 28 ] and Otmani et al.[ 29 ], who found no link between age and oral mucositis in pediatric patients. Figliolia et al.[ 21 ] reported no significant differences in mucositis; however, they did observe a higher frequency of oral mucositis (48%) in children aged ≤ 9 years compared to patients aged between 10 and 18 years (39%). This variance may stem from the larger sample size and the utilization of distinct age classification methods in our study. Additionally, younger children's elevated rate of cell division in oral mucosal tissue cells could be a contributing factor. Furthermore, the utilization of cytotoxic chemotherapy drugs can result in heightened cell apoptosis in normal oral mucosal tissue cells[ 30 ]. The study revealed a significant association between chemotherapy-induced oral mucositis and clinical risk stratification. High clinical risk stratification emerged as a protective factor against chemotherapy-induced oral mucositis in pediatric acute lymphoblastic leukemia. Our findings diverged from previous research[ 19 ]. The diagnosis and treatment of acute lymphoblastic leukemia adhere to the principle of individualization, classifying it into low risk, standard risk, and high risk categories[ 31 ]. Chemotherapy drug dosage, intensity, and frequency are determined based on differing clinical risk stratification[ 32 ]. This could be attributed to heightened monitoring of blood drug concentration in patients with high clinical risk stratification by medical staff. Moreover, pre-chemotherapy hydration levels are increased, emphasizing the need for increased attention to children with acute lymphoblastic leukemia of low clinical risk stratification. Regarding the association between chemotherapy cycles and oral mucositis, our findings indicate that children undergoing more than 5 courses of chemotherapy were at higher risk of developing oral mucositis compared to those undergoing 1 or 2 courses. Limited studies explore this relationship in children with acute lymphoblastic leukemia, hindering direct comparisons. A retrospective study in China suggests chemotherapy cycles significantly influence oral mucositis in patients with malignant tumors[ 33 ]. This could be attributed to escalating chemotherapy drug dosage and intensity with prolonged cycles, leading to extended exposure of oral mucosal tissues to high drug concentrations[ 15 ]. Furthermore, prolonged cycles may heighten the risk of myelosuppression in children with acute lymphoblastic leukemia, compromising their immunity and potentially resulting in oral mucositis[ 34 ]. Our study revealed a correlation between HSV-1 and Candida albicans and the development of oral mucositis in children with acute lymphoblastic leukemia, aligning with similar findings[ 16 – 18 ]. HSV-1, the predominant virus in the oral cavity, remains latent in the sacral ganglion and trigeminal ganglion and acts as an opportunistic pathogen[ 35 ]. Under normal immune conditions, it does not induce oral mucositis. However, children with acute lymphoblastic leukemia often undergo bone marrow suppression post-chemotherapy, leading to reduced blood cell count and weakened immunity, increasing their vulnerability to HSV-1 infection[ 16 – 18 ]. Furthermore, the oral microbial balance is disrupted due to reduced saliva production during chemotherapy, hampering oral cleansing, particularly when combined with antibiotic and glucocorticoid use[ 36 ]. Candida albicans, the prevalent oral fungus, frequently triggers oral mucositis in immunocompromised individuals[ 37 ]. Antifungal and antiviral drugs can be used preemptively to combat HSV-1 and Candida albicans[ 38 , 39 ]. Previous research has predominantly concentrated on the relationship between oral mucositis and the chemotherapy agent methotrexate[ 15 ]. However, there is a paucity of research examining the association between the incidence of oral mucositis in pediatric patients with acute lymphoblastic leukemia and alternative chemotherapeutic medications[ 15 ]. This study revealed that, apart from the chemotherapeutic agent methotrexate, cytarabine and daunorubicin also contributed to the onset of oral mucositis in pediatric patients with acute lymphoblastic leukemia. Methotrexate and cytarabine are anti-metabolism chemotherapeutic agents that eliminate tumor cells by disrupting cellular DNA synthesis and impeding cell proliferation[ 15 , 40 ]. However, methotrexate and cytarabine are also broad-spectrum antineoplastic agents capable of inflicting harm on healthy tissue cells while aiming at tumor cells. Specifically, they are particularly detrimental to tissue cells exhibiting a rapid rate of proliferation, such as oral mucosal tissue cells[ 15 , 40 ]. Daunorubicin is an anthracycline chemotherapeutic agent that influences diverse stages of cellular growth. However, it also induces considerable harm to normal oral mucosal tissue cells[ 41 ]. This suggests that clinical medical staff should pay more attention to monitoring blood drug concentration when administering these chemotherapy drugs. This implies that it is important for clinical medical staff to carefully monitor blood drug concentrations when administering chemotherapy drugs to ensure the safety and efficacy of the treatment. This can help minimize the risk of toxicity and ensure that the patient is receiving the appropriate therapeutic dose. Regular monitoring and adjustment of drug concentrations can be critical for optimizing the treatment outcomes for patients undergoing chemotherapy. Limitation This study retrospectively collected case data from two tertiary hospitals in Guangdong province. In future studies, it is advisable to consider conducting prospective cohort studies to identify more relevant risk factors and gather multi-center, large sample data for further analysis. Conclusion The high prevalence of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia underscores the need for clinical medical staff to conduct a comprehensive assessment, taking into account chemotherapy, microbiology, and other relevant factors pertaining to pediatric patients. It is imperative for them to implement appropriate preventive measures to mitigate the occurrence of chemotherapy-induced oral mucositis in this patient population. Declarations Funding: This work was supported by the project of Guangzhou Municipal Science and Technology, Grant/Award Number: 202201011758 and Sanming Project of Medicine in Shenzhen, Grant/Award Number: SZZYSM 202108013. Author Contribution Xiaofeng He, Weijie Wang designed the research. Xiaofeng He, Weijie Wang, Jiayin Huang, and Jing Zhang acquired and analyzed the data. Xiaofeng He drafted the manuscript. Lichan Liang, and Xiaomei Liao provided the site where the data was collected and technical guidance. Lei Shi revised the manuscript. References Dolya, Anastasia, Colombet, Murielle, Shin, Hee, Young, Ries, Lynn, and A. 2017. International incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol. (2017), 18(6): 719 – 31.DOI 10.1016/S1470-2045(17)30186-9 Xin Ni, Zhe Li, Xinping Li, Xiao Zhang, Guoliang Bai, Yingying Liu, Rongshou Zheng, Yawei Zhang, Xin Xu, Yuanhu Liu, Chenguang Jia, Huanmin Wang, Xiaoli Ma, Huyong Zheng, Yan Su, Ming Ge, Qi Zeng, Shengcai Wang, Junyang Zhao, Yueping Zeng, Guoshuang Feng, Yue Xi, Zhuo Deng, Yongli Guo, Zhuoyu Yang, and Jinzhe Zhang. 2022. Socioeconomic inequalities in cancer incidence and access to health services among children and adolescents in China: a cross-sectional study. 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Oral ulcers in children under chemotherapy: clinical characteristics and their relation with Herpes Simplex Virus type 1 and Candida albicans. Med Oral Patol Oral Cir Bucal (2005), E1. Stephen W. Mamber, Thomas Hatch, Craig S. Miller, John V. Murray, Cynthia Strout, and John McMichael. 2022. Low-dose Oral Thimerosal for the Treatment of Oral Herpes: Clinical Trial Results and Improved Outcome After Post-hoc Analysis. Journal of Evidence-Based Integrative Medicine (2022), 2210780X-2515690X. DOI 10.1177/2515690X221078004 Na Liu, Nan Zhang, Shengrong Zhang, Lifang Zhang, and Qing Liu. 2021. Phloretin inhibited the pathogenicity and virulence factors againstCandida albicans. Bioengineered (2021), 2420–2431. DOI 10.1080/21655979.2021.1933824 Takehiko Mori, Kaori Hasegawa, Ai Okabe, Natsuki Tsujimura, Yusuke Kawata, Tomoko Yashima, Naoko Kobayashi, Sakiko Kondo, Yoshinobu Aisa, Jun Kato, Kazuyuki Tsunoda, Tetsuo Nagai, Taneaki Nakagawa, Naoyuki Shigematsu, Atsushi Kubo, Yasuo Ikeda, and Shinichiro Okamoto. 2008. Efficacy of mouth rinse in preventing oral mucositis in patients receiving high-dose cytarabine for allogeneic hematopoietic stem cell transplantation. Int. J. Hematol. (2008), 583–587. DOI 10.1007/s12185-008-0181-5 Ye Chen, Saixian Shi, and Yan Dai. 2022. Research progress of therapeutic drugs for doxorubicin-induced cardiomyopathy. Biomed. Pharmacother. (2022), 113903. DOI 10.1016/j.biopha.2022.113903 Tables Tabel 1 Sociodemographic characteristics in chldren with acute lymphoblastic leukemia at two general hospital, Guangzhou, Guangdong, China, 2020-2022 Variables Category Frenquency(n) Percent（%） Age(years) < 6 302 64.3 ≥6 168 35.7 Sex Male 289 61.5 Female 181 38.5 Father’s level of education Primary school 60 12.8 Junior high school 160 34.0 Senior high school 114 24.3 Junior college 64 13.6 College or higher 72 15.3 Mother’s level of education Primary school 51 10.9 Junior high school 172 36.6 Senior high school 112 23.8 Junior college 58 12.3 College or higher 77 16.4 Monthly household income(RMB) < 5000 304 64.7 5000-9999 114 24.3 ≥10000 52 11.1 Tabel 2 Association between chemotherapy-induced oral mucositis and sociodemographic characteristics, nutritional data, disease and chemotherapy data, blood biochemical data, microbial, and oral and eating data in children with acute lymphoblastic leukemia Variables Presence of oral mucositis X 2 / t / Z value P-value Yes(n=212) No(n=258) Age(years) 15.298 <0.001* <6 116(54.71) 186(72.09) ≥6 96(45.29) 72(27.91) Father’s level of education -2.196 0.028* Primary school 26(12.30) 34(13.20) Junior high school 83(39.20) 77(29.80) Senior high school 58(27.40) 56(21.70) Junior college 19(9.0) 45(17.40) College or higher 26(12.30) 46(17.80) Monthly household income(RMB) -2.269 0.023* < 5000 148(69.80) 156(60.50) 5000-9999 47(22.20) 67(26.00) ≥10000 17(8.00) 35(13.60) Clinical risk stratification -3.678 <0.001* Low risk 95(44.80) 157(60.90) Standard risk 47(22.20) 49(19.00) High risk 70(33.00) 52(20.20) Immune stratification 5.541 0.019* T type 34(16.04) 23(8.91) B type 178(83.96) 235(91.09) Duration of disease -3.326 0.001* < 1 month 57(26.90) 43(16.70) 1-3 months 46(21.70) 50(19.40) 3-6 months 51(24.10) 62(24.00) ≥ 6 months 58(27.40) 103(39.90) Neutrophil count before chemotherapy(mm 3 ) 7.385 0.007* <1500 142(66.98) 141(54.65) ≥1500 70(33.02) 117(45.35) Platelet count before chemotherapy(mm 3 ) -2.312 0.021* <25 156(73.60) 163(63.20) 25-49 50(23.60) 88(34.10) 50-74 4(1.90) 5(1.90) ≥75 2(0.90) 2(0.80) Red blood cell count before chemotherapy (g/L) 2.96(2.47, 3.59) 3.17(2.65, 3.76) -2.126 0.033* Hemoglobin count before chemotherapy(×10 12 /L) 86.62±21.15 93.82±24.92 -3.334 0.001* Tabel 3Variable assignment for multivariate regression analysis Variables Assignment Dependent variable Chemotherapy induced oral mucositis No=0, Yes=1 Independent variable Age <6 yesrs=0, ≥6 yesrs=1 Father’s level of education Primary school=(0, 0, 0, 0), Junior high school=(1, 0, 0, 0), Senior high school=(0, 1, 0, 0), Junior college=(0, 0, 1, 0),College or higher =(0, 0, 0,1) Monthly household income <5000=(0, 0), 5000-9999=(1, 0), ≥10000=(0, 1) Clinical risk stratification IR=(0, 0), SR=(1, 0), HR=(0, 1) Immune stratification T type=0, B type=1 Duration of disease <1 month=(0, 0, 0), 1-3 months =(1, 0, 0), 3-6 months=(0, 1, 0), ≥6 months=(0, 0, 1) Neutrophil count before chemotherapy(/mm 3 ) <1500=0, ≥1500=1 Platelet count before chemotherapy(/mm 3 ) <25=(0, 0, 0), 25-49=(1, 0, 0), 50-74=(0, 1, 0), ≥75=(0, 0, 1) Accompanied by central or peripheral disease No=0，Yes=1 Treatment stage Induction period=(0, 0), Consolidation period=(1, 0), Maintenance period=(0, 1) Chemotherapy cycle 1-2 courses=(0, 0), 3-4 courses =(1, 0), ≥5 courses=(0, 1) Chemotherapy drug containing MTX/DNR/Ara-C No=0，Yes=1 Carrying HSV-1 No=0, Yes=1 Being infected with Candida albicans No=0, Yes=1 Frequency of preventive gargle before chemotherapy <1 time=(0, 0), 1-2 times=(1, 0), ≥3 times=(0, 1) Number of meals per day during chemotherapy <1 time=(0, 0), 1-2 times=(1, 0), ≥3 times=(0, 1) Tabel 4 Association between chemotherapy-induced oral mucositis and age, clinical risk stratification, chemotherpy cycle, chemotherapy drug, HSV-1, and Candida albicans Variables β SE Wald-value P -value OR - value 95%CI Age ≥ 6 years -0.694 0.222 9.787 0.002 0.499 (0.323, 0.772) Low clinical risk stratification - - 9.416 0.009 - - Standard clinical risk stratification -0.204 0.281 0.524 0.469 0.816 (0.470, 1.415) High clinical risk stratification -0.778 0.254 9.375 0.002 0.459 (0.279, 0.756) Chemotherapy cycle 1-2 courses - - 15.591 <0.001 - - Chemotherapy cycle 3-4 courses 0.573 0.365 2.466 0.116 1.773 (0.868, 3.623) Chemotherapy cycle ≥ 5 courses 0.967 0.245 15.546 <0.001 2.631 (1.627, 4.255) Chemotherapy drug contains MTX/DNR/Ara-C 1.787 0.367 23.647 <0.001 5.972 (2.906, 12.272) Carrying HSV-1 2.574 1.073 5.755 0.016 13.117 (1.601, 107.438) Being infected with Candida albicans 1.829 0.730 6.280 0.012 6.229 (1.490, 26.044) Additional Declarations No competing interests reported. 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In China, more than 120, 000 children and adolescents aged 0 to 19 years were diagnosed with cancer between 2018 and 2020, and on average, more than 40, 000 children were newly diagnosed with cancer each year[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. According to statistics, the incidence of childhood cancer has been increasing by 2.8% per year for nearly a decade[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Acute lymphoblastic leukemia is one of the most common types of childhood cancer and childhood leukemia, accounting for 26% of cancer cases in children aged 0 to 14[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], 55.82% of leukemia cases in children and adolescents aged 0 to 19 years and approximately 75% of newly diagnosed leukemia[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. As treatment technology is being constantly improved, the 5-year survival rate for patients with acute lymphoblastic leukemia has increased from 57\u0026ndash;90%[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. At present, the focus has now shifted towards achieving early remission and addressing long-term complications of the disease[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The emphasis on chemotherapy as the main treatment also highlights the need to address its associated complications, such as oral mucositis as mentioned earlier[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn comparison to adult cancer patients, pediatric cancer patients are more susceptible to developing oral mucositis[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The incidence of oral mucositis among pediatric cancer patients ranges from 33\u0026ndash;80%[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Furthermore, after high-dose methotrexate chemotherapy, the incidence of oral mucositis in these patients can reach 74.9%[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Moreover, the incidence of oral mucositis in children with hematologic tumors is significantly higher, ranging from 7.0 to 7.1 times than those of children with other tumors[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This warrants particular attention given that acute lymphoblastic leukemia is the most prevalent hematologic tumor in children[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe clinical symptoms of oral mucositis encompass atrophy, redness, ulceration, and bleeding accompanied by pain, which can lead to secondary infection or systemic infection, disruption of chemotherapy, prolonged hospital stays, and malnutrition[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Additionally, oral mucositis imposes a significant psychological burden on patients, often being regarded as the most undesirable event during chemotherapy treatment[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This emotional impact may lead to negative emotions in patients and influence treatment quality and patient compliance[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e Substantial advancements have been achieved in comprehending the pathobiology of oral mucositis. Oral mucositis does not simply result from epithelial cell injury; rather, its mechanism comprises five stages: initiation, signal transmission, amplification, ulceration, and healing[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The pathogenesis of oral mucositis is complex, and currently, none of the preventive measures are effective in addressing the entire process[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Identifying the risk factors associated with chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia is crucial for developing effective, targeted interventions to prevent or delay its onset and development.\u003c/p\u003e \u003cp\u003eThe relevant risk factors of oral mucositis in children with acute lymphoblastic leukemia have been described in the existing literature. We carried out a systematic review to understand the risk factors of oral mucositis in children with acute lymphoblastic leukemia[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Factors related to oral mucositis mainly include patient-related factors and treatment-related factors[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, the treatment-related risk factors of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia remain poorly understood. For example, the majority of relevant studies solely focus on the relationship between the chemotherapy drug methotrexate and oral mucositis in children with acute lymphoblastic leukemia, but there is a lack of studies investigating the correlation between the development of oral mucositis and other chemotherapeutic agents. Additionally, most studies only focus on one-sided influencing factors. Maiguma et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]detailed the relationship between high-dose methotrexate therapy and oral mucositis in pediatric acute lymphoblastic leukemia. De Mendon\u0026ccedil;a et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]indicated that the presence of HSV, mainly HSV-1, and Candida spp. were associated with mucositis severity in pediatric acute lymphoblastic leukemia. Santos et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]implied that HSV-1 may be a risk factor for aggravating the severity of mucositis. Mendon\u0026ccedil;a et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]revealed that the presence of HSV, platelet count, neutrophil count, and Candida spp. were associated with increased severity of mucositis in children with acute lymphoblastic leukemia. Murshid et al. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]uncovered a strong correlation between practice frequency of oral hygiene practice and dietary habits and the developmental severity of oral mucositis in children with acute lymphoblastic leukemia. Devi et al.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] reported the relationship between oral care practice at home and oral mucositis incidence. Figliolia et al.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] found the ALL-BFM-95 protocol was associated with the development of oral mucositis in children with acute lymphoblastic leukemia. Gutierrez-Camino et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]reported that miRNA-4268 rs4674470AA\u0026thinsp;+\u0026thinsp;AG\u0026thinsp;+\u0026thinsp;GG linked to oral mucositis development in children with acute lymphoblastic leukemia.\u003c/p\u003e \u003cp\u003e The objective of this study was to comprehensively investigate the prevalence and risk factors of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia in China, and to gain a better understanding of treatment-related risk factors.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe retrospective study included 470 children diagnosed with acute lymphoblastic leukemia who received treatment at the pediatric departments of two tertiary hospitals in southern China between January 2020 and July 2022. The study's inclusion criteria were as follows: (a) patients aged 0 to 18 years; (b) diagnosis of acute lymphoblastic leukemia based on the SCCLG-2016 ALL protocol[\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]; (c) absence of oral mucositis before chemotherapy according to the World Health Organization criteria for oral mucositis[\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]; (d) normal communication ability and consent from patients' caregivers; and (e) primary caregivers knowledgeable about patients' oral and dietary condition. Exclusion criteria encompassed patients with other malignant tumors or serious diseases of vital organs. The research obtained approval from the Biomedical Ethics Committee of Southern Medical University ( [2022] No.011) and adhered to the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003eMeasures variables\u003c/h2\u003e\n\u003cp\u003eA risk factor questionnaire was developed based on a systematic review and the incorporation of clinical expert opinion[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. It encompassed the following categories:\u003c/p\u003e\n\u003cp\u003e(a) Sociodemographic data: This included the age of patients at diagnosis, sex, father's level of education, mother's level of education, and monthly household income. (b) Nutritional data: The body mass index for age Z-score ((BMI measured value - data median) / data standard deviation) was utilized to assess the nutritional status of patients. This measure was recommended by the World Health Organization to evaluate body size changes in children. In this study, the most recent body mass index for age Z-score before chemotherapy was used. (c) Disease and chemotherapy data: This category encompassed clinical risk stratification, immune stratification, disease duration, disease location (central or peripheral), treatment stage, recurrence, chemotherapy cycle, and chemotherapy drugs containing MTX/DNR/Ara-C. (d) Blood biochemical data: Parameters included the count of white blood cells at diagnosis, as well as the counts of white blood cells, red blood cells, hemoglobin, platelets, and neutrophils before chemotherapy. The measurements taken one day before chemotherapy were utilized. (e) Microbial data: This section captured whether the patient carried HSV-1 or was infected with Candida albicans during previous or current chemotherapy sessions.(f) Oral and dietary data: Information regarding the frequency of preventive mouthwash before chemotherapy, the number of meals per day during chemotherapy, the main food type per day during chemotherapy, toothbrush type during chemotherapy, and previous history of oral mucositis, dental caries, periodontitis, or gingivitis.\u003c/p\u003e\n\u003cp\u003eThe diagnosis of oral mucositis was conducted using the World Health Organization's criteria: grade 0\u0026thinsp;=\u0026thinsp;no mucositis, grade 1\u0026thinsp;=\u0026thinsp;erythema without lesions, grade 2\u0026thinsp;=\u0026thinsp;ulcers, but able to eat, grade 3\u0026thinsp;=\u0026thinsp;painful ulcers, but able to intake liquid food, grade 4\u0026thinsp;=\u0026thinsp;unable to eat by mouth.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003eData collection\u003c/h2\u003e\n\u003cp\u003eThe researchers collected medical record data of children following standardized training. To obtain oral and dietary data, caregivers who were familiar with the children's conditions were approached. In cases where children had been discharged, researchers utilized field investigations or telephone follow-ups, depending on whether the children were at home or in the hospital, to gather relevant information. Pediatricians documented the onset time and symptoms of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia. In an effort to minimize subjective bias, the severity of oral mucositis was evaluated by uninformed researchers who had undergone uniform training.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003eData analyses\u003c/h2\u003e\n\u003cp\u003eThe statistical data were analyzed using IBM SPSS 26.0 software. The Chi-square test was employed to examine the relationship between the occurrence of oral mucositis and quantitative data, including age at diagnosis, sex, and immune classification. An independent t-test was conducted to identify the correlation between the occurrence of oral mucositis and measures of red blood cell count and hemoglobin level. The Wilcoxon test was utilized to analyze the relationship between the occurrence of oral mucositis and other ordinal variables. Variables with a P-value less than 0.05 in the univariate analysis were included in the multivariate logistic regression model for further discussion, and the stepwise backward method was employed to identify independent risk factors. The significance level was set at 0.05.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eSociodemographic characteristics\u003c/h2\u003e \u003cp\u003eThe sociodemographic characteristics of the children with acute lymphoblastic leukemia are summarized in Table\u0026nbsp;1. Among the 470 children analyzed, 289 (61.5%) were male and 181 (38.5%) were female. Their ages ranged from 0 to 17 years, with a mean age of 4.00 (3.00\u0026thinsp;~\u0026thinsp;7.00) years. Among the 470 children, 212 developed chemotherapy-induced oral mucositis, resulting in a prevalence of 45.1%. Of these cases, 138 were classified as grade Ⅰ, 43 as grade Ⅱ, 14 as grade Ⅲ, and 17 as grade Ⅳ.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eThe results of univariate analysis\u003c/h2\u003e \u003cp\u003eThe results of the univariate analysis are summarized in Table\u0026nbsp;2. Statistically significant differences were observed in various factors, including age, father's level of education, monthly household income, clinical risk classification, immune classification, duration of disease, count of red blood cells, hemoglobin, platelets, and neutrophils before chemotherapy. Additionally, factors such as the presence of central or peripheral disease, treatment stage, chemotherapy cycle, specific chemotherapy drugs, presence of HSV-1, infection with candida albicans, frequency of preventive mouthwash before chemotherapy, and number of meals per day during chemotherapy also showed statistically significant associations (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eThe results of multivariate logistic regression analysis\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;3 displays the variable assignment, while Table\u0026nbsp;4 presents the results of the multivariate logistic regression analysis. Factors influencing the outcome included receiving more than 5 courses of chemotherapy (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.631, \u003cem\u003e95%CI\u003c/em\u003e: 1.627\u0026ndash;4.255, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), HSV-1 infection (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;13.117, \u003cem\u003e95%CI\u003c/em\u003e: 1.601-107.438, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016), Candida albicans infection (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.229, \u003cem\u003e95%CI\u003c/em\u003e: 1.490-26.044, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012), use of chemotherapy drugs containing MTX/DNR/Ara-C (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.972, \u003cem\u003e95%CI\u003c/em\u003e: 2.906\u0026ndash;12.272, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), high clinical risk stratification (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.459, \u003cem\u003e95%CI\u003c/em\u003e: 0.279\u0026ndash;0.756, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), and being over 6 years old (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.499, \u003cem\u003e95%CI\u003c/em\u003e: 0.323\u0026ndash;0.772, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002).\u003c/p\u003e \u003c/div\u003e"},{"header":"Disscusion","content":"\u003cp\u003eOral mucositis is the most common oral complication in children with acute lymphoblastic leukemia[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Factors contributing to oral mucositis mainly encompass patient-related and treatment-related factors[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Yet, the risk factors associated with treatment in children with acute lymphoblastic leukemia have not been comprehensively investigated. This study aimed to explore the incidence and risk factors of chemotherapy-induced oral mucositis in Chinese children with acute lymphoblastic leukemia. Additionally, it sought to offer deeper insights into the treatment-related risk factors.\u003c/p\u003e \u003cp\u003eOur findings were consistent with previous studies that have reported a relatively high incidence of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia[\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. This study observed a 45.1% incidence of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia. Figliolia et al.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] reported a 46% incidence and Devi et al.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] also found a 48.7% incidence of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia. However, our findings demonstrated higher incidences compared to those reported by Murshid et al. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]and Azher et al[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]; Murshid et al.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] reported a 23.3% incidence, while Azher et al.[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] reported a 20.0% incidence. This disparity may be attributed to the fact that the studies by Murshid et al. and Azher et al. only focused on children with acute lymphoblastic leukemia during the induction period.\u003c/p\u003e \u003cp\u003eIn our study, we observed a notable correlation between age at diagnosis and chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia. Children aged 6 years and above were found to have a lower risk of chemotherapy-induced oral mucositis. These findings contrasted with those of comparable studies, such as Figliolia et al.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], Cheng et al.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], Fadda et al.[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and Otmani et al.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], who found no link between age and oral mucositis in pediatric patients. Figliolia et al.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] reported no significant differences in mucositis; however, they did observe a higher frequency of oral mucositis (48%) in children aged\u0026thinsp;\u0026le;\u0026thinsp;9 years compared to patients aged between 10 and 18 years (39%). This variance may stem from the larger sample size and the utilization of distinct age classification methods in our study. Additionally, younger children's elevated rate of cell division in oral mucosal tissue cells could be a contributing factor. Furthermore, the utilization of cytotoxic chemotherapy drugs can result in heightened cell apoptosis in normal oral mucosal tissue cells[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe study revealed a significant association between chemotherapy-induced oral mucositis and clinical risk stratification. High clinical risk stratification emerged as a protective factor against chemotherapy-induced oral mucositis in pediatric acute lymphoblastic leukemia. Our findings diverged from previous research[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The diagnosis and treatment of acute lymphoblastic leukemia adhere to the principle of individualization, classifying it into low risk, standard risk, and high risk categories[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Chemotherapy drug dosage, intensity, and frequency are determined based on differing clinical risk stratification[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. This could be attributed to heightened monitoring of blood drug concentration in patients with high clinical risk stratification by medical staff. Moreover, pre-chemotherapy hydration levels are increased, emphasizing the need for increased attention to children with acute lymphoblastic leukemia of low clinical risk stratification.\u003c/p\u003e \u003cp\u003eRegarding the association between chemotherapy cycles and oral mucositis, our findings indicate that children undergoing more than 5 courses of chemotherapy were at higher risk of developing oral mucositis compared to those undergoing 1 or 2 courses. Limited studies explore this relationship in children with acute lymphoblastic leukemia, hindering direct comparisons. A retrospective study in China suggests chemotherapy cycles significantly influence oral mucositis in patients with malignant tumors[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. This could be attributed to escalating chemotherapy drug dosage and intensity with prolonged cycles, leading to extended exposure of oral mucosal tissues to high drug concentrations[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Furthermore, prolonged cycles may heighten the risk of myelosuppression in children with acute lymphoblastic leukemia, compromising their immunity and potentially resulting in oral mucositis[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study revealed a correlation between HSV-1 and Candida albicans and the development of oral mucositis in children with acute lymphoblastic leukemia, aligning with similar findings[\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. HSV-1, the predominant virus in the oral cavity, remains latent in the sacral ganglion and trigeminal ganglion and acts as an opportunistic pathogen[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Under normal immune conditions, it does not induce oral mucositis. However, children with acute lymphoblastic leukemia often undergo bone marrow suppression post-chemotherapy, leading to reduced blood cell count and weakened immunity, increasing their vulnerability to HSV-1 infection[\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Furthermore, the oral microbial balance is disrupted due to reduced saliva production during chemotherapy, hampering oral cleansing, particularly when combined with antibiotic and glucocorticoid use[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Candida albicans, the prevalent oral fungus, frequently triggers oral mucositis in immunocompromised individuals[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Antifungal and antiviral drugs can be used preemptively to combat HSV-1 and Candida albicans[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrevious research has predominantly concentrated on the relationship between oral mucositis and the chemotherapy agent methotrexate[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, there is a paucity of research examining the association between the incidence of oral mucositis in pediatric patients with acute lymphoblastic leukemia and alternative chemotherapeutic medications[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. This study revealed that, apart from the chemotherapeutic agent methotrexate, cytarabine and daunorubicin also contributed to the onset of oral mucositis in pediatric patients with acute lymphoblastic leukemia. Methotrexate and cytarabine are anti-metabolism chemotherapeutic agents that eliminate tumor cells by disrupting cellular DNA synthesis and impeding cell proliferation[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. However, methotrexate and cytarabine are also broad-spectrum antineoplastic agents capable of inflicting harm on healthy tissue cells while aiming at tumor cells. Specifically, they are particularly detrimental to tissue cells exhibiting a rapid rate of proliferation, such as oral mucosal tissue cells[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Daunorubicin is an anthracycline chemotherapeutic agent that influences diverse stages of cellular growth. However, it also induces considerable harm to normal oral mucosal tissue cells[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. This suggests that clinical medical staff should pay more attention to monitoring blood drug concentration when administering these chemotherapy drugs. This implies that it is important for clinical medical staff to carefully monitor blood drug concentrations when administering chemotherapy drugs to ensure the safety and efficacy of the treatment. This can help minimize the risk of toxicity and ensure that the patient is receiving the appropriate therapeutic dose. Regular monitoring and adjustment of drug concentrations can be critical for optimizing the treatment outcomes for patients undergoing chemotherapy.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eLimitation\u003c/h2\u003e \u003cp\u003eThis study retrospectively collected case data from two tertiary hospitals in Guangdong province. In future studies, it is advisable to consider conducting prospective cohort studies to identify more relevant risk factors and gather multi-center, large sample data for further analysis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe high prevalence of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia underscores the need for clinical medical staff to conduct a comprehensive assessment, taking into account chemotherapy, microbiology, and other relevant factors pertaining to pediatric patients. It is imperative for them to implement appropriate preventive measures to mitigate the occurrence of chemotherapy-induced oral mucositis in this patient population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis work was supported by the project of Guangzhou Municipal Science and Technology, Grant/Award Number: 202201011758 and Sanming Project of Medicine in Shenzhen, Grant/Award Number: SZZYSM 202108013.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eXiaofeng He, Weijie Wang designed the research. Xiaofeng He, Weijie Wang, Jiayin Huang, and Jing Zhang acquired and analyzed the data. Xiaofeng He drafted the manuscript. Lichan Liang, and Xiaomei Liao provided the site where the data was collected and technical guidance. Lei Shi revised the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDolya, Anastasia, Colombet, Murielle, Shin, Hee, Young, Ries, Lynn, and A. 2017. 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DOI \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.biopha.2022.113903\u003c/span\u003e\u003cspan address=\"10.1016/j.biopha.2022.113903\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTabel 1 Sociodemographic characteristics in chldren with acute lymphoblastic leukemia at two general hospital, Guangzhou, Guangdong, China, 2020-2022\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003eCategory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003eFrenquency(n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003ePercent（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003eAge(years)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e302\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e64.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026ge;6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e168\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e35.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e61.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e181\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e38.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003eFather\u0026rsquo;s level of education\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003ePrimary school\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e12.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003eJunior high school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e34.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003eSenior high school\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e24.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003eJunior college\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003eCollege or higher\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e15.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003eMother\u0026rsquo;s level of education\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003ePrimary school\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003eJunior high school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e172\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e36.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003eSenior high school\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e23.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003eJunior college\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e12.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003eCollege or higher\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e16.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003eMonthly household income(RMB)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 5000\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e304\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e64.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003e5000-9999\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e24.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.013698630136986%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.061643835616437%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026ge;10000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.006849315068493%\" valign=\"top\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91780821917808%\" valign=\"top\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTabel 2 Association between chemotherapy-induced oral mucositis and sociodemographic characteristics, nutritional data, disease and chemotherapy data, blood biochemical data, microbial, and oral and eating data in children with acute lymphoblastic leukemia\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"588\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\" rowspan=\"2\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.285714285714285%\" colspan=\"2\"\u003e\n \u003cp\u003ePresence of oral mucositis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\" rowspan=\"2\"\u003e\n \u003cp\u003eX\u003csup\u003e2\u003c/sup\u003e/\u003cem\u003et\u003c/em\u003e/\u003cem\u003eZ\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eP-value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.38095238095238%\"\u003e\n \u003cp\u003eYes(n=212)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.61904761904762%\"\u003e\n \u003cp\u003e\u0026nbsp;No(n=258)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eAge(years)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\n \u003cp\u003e15.298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003e\u0026lt;6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e116(54.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e186(72.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003e\u0026ge;6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e96(45.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e72(27.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\" valign=\"top\"\u003e\n \u003cp\u003eFather\u0026rsquo;s level of education\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\n \u003cp\u003e-2.196\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\n \u003cp\u003e0.028*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\" valign=\"top\"\u003e\n \u003cp\u003ePrimary school\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\" valign=\"top\"\u003e\n \u003cp\u003e26(12.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\" valign=\"top\"\u003e\n \u003cp\u003e34(13.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\" valign=\"top\"\u003e\n \u003cp\u003eJunior high school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\" valign=\"top\"\u003e\n \u003cp\u003e83(39.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\" valign=\"top\"\u003e\n \u003cp\u003e77(29.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\" valign=\"top\"\u003e\n \u003cp\u003eSenior high school\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\" valign=\"top\"\u003e\n \u003cp\u003e58(27.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\" valign=\"top\"\u003e\n \u003cp\u003e56(21.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\" valign=\"top\"\u003e\n \u003cp\u003eJunior college\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\" valign=\"top\"\u003e\n \u003cp\u003e19(9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\" valign=\"top\"\u003e\n \u003cp\u003e45(17.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\" valign=\"top\"\u003e\n \u003cp\u003eCollege or higher\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\" valign=\"top\"\u003e\n \u003cp\u003e26(12.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\" valign=\"top\"\u003e\n \u003cp\u003e46(17.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eMonthly household income(RMB)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\n \u003cp\u003e-2.269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\n \u003cp\u003e0.023*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 5000\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e148(69.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e156(60.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\" valign=\"top\"\u003e\n \u003cp\u003e5000-9999\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e47(22.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e67(26.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026ge;10000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e17(8.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e35(13.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eClinical risk stratification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\n \u003cp\u003e-3.678\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eLow risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e95(44.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e157(60.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eStandard risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e47(22.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e49(19.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eHigh risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e70(33.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e52(20.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eImmune stratification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\n \u003cp\u003e5.541\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\n \u003cp\u003e0.019*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eT type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e34(16.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e23(8.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eB type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e178(83.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e235(91.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eDuration of disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\n \u003cp\u003e-3.326\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003e\u0026lt; 1 month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e57(26.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e43(16.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003e1-3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e46(21.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e50(19.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003e3-6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e51(24.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e62(24.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003e\u0026ge;\u0026nbsp;6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e58(27.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e103(39.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eNeutrophil count before chemotherapy(mm\u003csup\u003e3\u003c/sup\u003e)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\n \u003cp\u003e7.385\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\n \u003cp\u003e0.007*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003e\u0026lt;1500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e142(66.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e141(54.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003e\u0026ge;1500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e70(33.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e117(45.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003ePlatelet count before chemotherapy(mm\u003csup\u003e3\u003c/sup\u003e)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\n \u003cp\u003e-2.312\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\n \u003cp\u003e0.021*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003e\u0026lt;25\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e156(73.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e163(63.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003e25-49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e50(23.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e88(34.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003e50-74\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e4(1.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e5(1.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003e\u0026ge;75\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e2(0.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e2(0.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eRed blood cell count before chemotherapy (g/L)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e2.96(2.47, 3.59)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e3.17(2.65, 3.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\n \u003cp\u003e-2.126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\n \u003cp\u003e0.033*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.224489795918366%\"\u003e\n \u003cp\u003eHemoglobin count before chemotherapy(\u0026times;10\u003csup\u003e12\u003c/sup\u003e/L)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.578231292517007%\"\u003e\n \u003cp\u003e86.62\u0026plusmn;21.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.707482993197278%\"\u003e\n \u003cp\u003e93.82\u0026plusmn;24.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.945578231292517%\"\u003e\n \u003cp\u003e-3.334\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54421768707483%\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTabel 3Variable assignment for multivariate regression analysis\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"581\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003eAssignment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\n \u003cp\u003eDependent variable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eChemotherapy induced oral mucositis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003eNo=0, Yes=1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\n \u003cp\u003eIndependent variable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;6 yesrs=0,\u0026nbsp;\u0026ge;6 yesrs=1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eFather\u0026rsquo;s level of education\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003ePrimary school=(0, 0, 0, 0), Junior high school=(1, 0, 0, 0), Senior high school=(0, 1, 0, 0), Junior college=(0, 0, 1, 0),College\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;or higher =(0, 0, 0,1) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eMonthly household income\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;5000=(0, 0), 5000-9999=(1, 0), \u0026nbsp;\u0026ge;10000=(0, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eClinical risk stratification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003eIR=(0, 0), SR=(1, 0), HR=(0, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eImmune stratification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003eT type=0, B type=1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eDuration of disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;1 month=(0, 0, 0), 1-3 months\u003c/p\u003e\n \u003cp\u003e=(1, 0, 0), 3-6 months=(0, 1, 0),\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u0026ge;6 months=(0, 0, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eNeutrophil count before chemotherapy(/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;1500=0, \u0026nbsp;\u0026ge;1500=1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003ePlatelet count before chemotherapy(/mm\u003csup\u003e3\u003c/sup\u003e)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;25=(0, 0, 0), 25-49=(1, 0, 0), 50-74=(0, 1, 0),\u0026nbsp;\u0026ge;75=(0, 0, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eAccompanied by central\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eor peripheral disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003eNo=0，Yes=1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eTreatment stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003eInduction period=(0, 0), Consolidation period=(1, 0), Maintenance period=(0, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eChemotherapy cycle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003e1-2 courses=(0, 0), 3-4 courses\u003c/p\u003e\n \u003cp\u003e=(1, 0),\u0026nbsp;\u0026ge;5 courses=(0, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eChemotherapy drug containing MTX/DNR/Ara-C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003eNo=0，Yes=1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eCarrying HSV-1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003eNo=0, Yes=1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eBeing infected with Candida albicans\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003eNo=0, Yes=1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eFrequency of preventive gargle before chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;1 time=(0, 0), 1-2 times=(1, 0),\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u0026ge;3 times=(0, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06368330464716%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.55421686746988%\" valign=\"top\"\u003e\n \u003cp\u003eNumber of meals per day during chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.38209982788296%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;1 time=(0, 0), 1-2 times=(1, 0),\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u0026ge;3 times=(0, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTabel 4 Association between chemotherapy-induced oral mucositis and age, clinical risk stratification, chemotherpy cycle, chemotherapy drug, HSV-1, and Candida albicans\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"651\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.36196319018405%\" valign=\"top\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026beta;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eSE\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.269938650306749%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eWald-value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.815950920245399%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eOR\u003c/em\u003e-\u003cem\u003evalue\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.87116564417178%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e95%CI\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.36196319018405%\" valign=\"top\"\u003e\n \u003cp\u003eAge\u0026nbsp;\u0026ge;\u0026nbsp;6 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e-0.694\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.269938650306749%\" valign=\"top\"\u003e\n \u003cp\u003e9.787\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.815950920245399%\" valign=\"top\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\" valign=\"top\"\u003e\n \u003cp\u003e0.499\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.87116564417178%\" valign=\"top\"\u003e\n \u003cp\u003e(0.323, 0.772)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.36196319018405%\" valign=\"top\"\u003e\n \u003cp\u003eLow clinical risk stratification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.269938650306749%\" valign=\"top\"\u003e\n \u003cp\u003e9.416\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.815950920245399%\" valign=\"top\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.87116564417178%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.36196319018405%\" valign=\"top\"\u003e\n \u003cp\u003eStandard clinical risk stratification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e-0.204\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e0.281\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.269938650306749%\" valign=\"top\"\u003e\n \u003cp\u003e0.524\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.815950920245399%\" valign=\"top\"\u003e\n \u003cp\u003e0.469\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\" valign=\"top\"\u003e\n \u003cp\u003e0.816\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.87116564417178%\" valign=\"top\"\u003e\n \u003cp\u003e(0.470, 1.415)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.36196319018405%\" valign=\"top\"\u003e\n \u003cp\u003eHigh clinical risk stratification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e-0.778\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e0.254\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.269938650306749%\" valign=\"top\"\u003e\n \u003cp\u003e9.375\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.815950920245399%\" valign=\"top\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\" valign=\"top\"\u003e\n \u003cp\u003e0.459\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.87116564417178%\" valign=\"top\"\u003e\n \u003cp\u003e(0.279, 0.756)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.36196319018405%\" valign=\"top\"\u003e\n \u003cp\u003eChemotherapy cycle 1-2 courses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.269938650306749%\" valign=\"top\"\u003e\n \u003cp\u003e15.591\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.815950920245399%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.87116564417178%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.36196319018405%\" valign=\"top\"\u003e\n \u003cp\u003eChemotherapy cycle 3-4 courses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e0.573\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e0.365\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.269938650306749%\" valign=\"top\"\u003e\n \u003cp\u003e2.466\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.815950920245399%\" valign=\"top\"\u003e\n \u003cp\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\" valign=\"top\"\u003e\n \u003cp\u003e1.773\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.87116564417178%\" valign=\"top\"\u003e\n \u003cp\u003e(0.868, 3.623)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.36196319018405%\" valign=\"top\"\u003e\n \u003cp\u003eChemotherapy cycle\u0026nbsp;\u0026ge;\u0026nbsp;5 courses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e0.967\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e0.245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.269938650306749%\" valign=\"top\"\u003e\n \u003cp\u003e15.546\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.815950920245399%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\" valign=\"top\"\u003e\n \u003cp\u003e2.631\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.87116564417178%\" valign=\"top\"\u003e\n \u003cp\u003e(1.627, 4.255)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.36196319018405%\" valign=\"top\"\u003e\n \u003cp\u003eChemotherapy drug contains MTX/DNR/Ara-C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e1.787\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e0.367\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.269938650306749%\" valign=\"top\"\u003e\n \u003cp\u003e23.647\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.815950920245399%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\" valign=\"top\"\u003e\n \u003cp\u003e5.972\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.87116564417178%\" valign=\"top\"\u003e\n \u003cp\u003e(2.906, 12.272)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.36196319018405%\" valign=\"top\"\u003e\n \u003cp\u003eCarrying HSV-1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e2.574\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e1.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.269938650306749%\" valign=\"top\"\u003e\n \u003cp\u003e5.755\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.815950920245399%\" valign=\"top\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\" valign=\"top\"\u003e\n \u003cp\u003e13.117\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.87116564417178%\" valign=\"top\"\u003e\n \u003cp\u003e(1.601, 107.438)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.36196319018405%\" valign=\"top\"\u003e\n \u003cp\u003eBeing infected with\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCandida albicans\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e1.829\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.282208588957054%\" valign=\"top\"\u003e\n \u003cp\u003e0.730\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.269938650306749%\" valign=\"top\"\u003e\n \u003cp\u003e6.280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.815950920245399%\" valign=\"top\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\" valign=\"top\"\u003e\n \u003cp\u003e6.229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.87116564417178%\" valign=\"top\"\u003e\n \u003cp\u003e(1.490, 26.044)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Acute lymphoblastic leukemia, Chemotherapy, Oral mucositis, Risk factor","lastPublishedDoi":"10.21203/rs.3.rs-4256541/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4256541/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eTo comprehensively assess the prevalence and risk factors of chemotherapy-induced oral mucositis in 470 children diagnosed with acute lymphoblastic leukemia in China, and to gain a better understanding of the treatment-related risk factors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eIn this retrospective study, 470 children diagnosed with acute lymphoblastic leukemia in China between January 2020 and July 2022 were included. Data on sociodemographic characteristics, nutritional status, disease and treatment history, blood biochemistry, and microbiological factors were gathered using electronic medical records, alongside oral and dietary information collected through field investigations and telephone follow-ups. The association between chemotherapy-induced oral mucositis and these variables was assessed using univariate and multivariate logistic analyses.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe study found a high prevalence (45.1%) of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia. The occurrence of oral mucositis was associated with several factors, including receiving more than five chemotherapy cycles (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001), carrying HSV-1(\u003cem\u003eP\u003c/em\u003e=0.016), being infected with Candida albicans(\u003cem\u003eP\u003c/em\u003e=0.012), undergoing chemotherapy with specific drugs containing methotrexate/daunorubicin/cytarabine(\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001), having a high clinical risk stratification(\u003cem\u003eP\u003c/em\u003e=0.002), and being over 6 years old(\u003cem\u003eP\u003c/em\u003e=0.002).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe study suggests that the prevalence of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia is relatively high. It emphasizes the importance of clinical medical staff paying attention to this issue and adopting targeted interventions to reduce the prevalence of oral mucositis in this patient population.\u003c/p\u003e","manuscriptTitle":"Prevalence and risk factors of chemotherapy-induced oral mucositis in 470 children with acute lymphoblastic leukemia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-30 14:56:22","doi":"10.21203/rs.3.rs-4256541/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d47603b2-d0a7-4ff9-8eb1-dd9b7e0d0033","owner":[],"postedDate":"April 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-31T03:38:52+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-30 14:56:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4256541","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4256541","identity":"rs-4256541","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}