| Background:Acute lymphoblastic leukemia(ALL)is a common malignant disease in Chinese children.In recent years,the survival rate of ALL children has been significantly improved due to the application and continuous improvement of combined chemotherapy regimens.However,there are still patients who have treatment failure due to recurrence,treatment-related death and second cancer.Infection was the leading cause of treatment-related death in children with bone marrow remission.Maintenance therapy is an important part of ALL chemotherapy.We found in clinical work that although the intensity of chemotherapy in the middle and late stages of maintenance therapy is low,ALL children in this stage can still be complicated with severe infection,which affects their prognosis and quality of life.At present,the research on severe infection in ALL children mainly focuses on the induction remission and consolidation treatment stage,and the analysis of severe infection in the middle and late stages of maintenance treatment is rare.Objective:To analyze the severe infection in children with ALL who received chemotherapy under CCCG-ALL-2015 regimen during the middle and late period of maintenance treatment,and to study the clinical characteristics,risk factors and their influence on the prognosis of children with ALL,so as to increase the understanding of severe infection during this stage of chemotherapy and improve its treatment and prevention.Methods:A total of 268 cases of newly diagnosed and treated ALL children admitted to Qilu Hospital of Shandong University from January 2015 to January 2020 were included after standard screening.The clinical data of 268 children who were hospitalized in Qilu Hospital of Shandong University from May 2016 to December 2022 due to severe infection during the middle and late period of maintenance treatment were retrospectively studied.The occurrence time,length of stay,clinical manifestations,infection site and other characteristics of severe infection in children were analyzed.SPSS 26.0 statistical software was used for data processing.The measurement data between the two groups were compared by t test or non-parametric test.The univariate analysis of risk factors were performed by chi-square test or Fisher exact probability method.Logistic regression model was used to screen the risk factors.Kaplan-Meier survival analysis was used for EFS and OS,and Log-rank test was used to analyze the effect of severe infection on OS and EFS.P<0.05 was defined as statistically significant.Results:1.General information:Among the 268 children,169(63.1%)were males,99(36.9%)were females,246 were B-ALL.20 were T-ALL.172 were in the standard-risk group,of which 93 were treated with LR-A chemotherapy regimen and 79 were treated with LR-B chemotherapy regimen.There were 93 children in the medium-risk group,3 children in the high-risk group.60 children in the medium-risk group were treated with the I/HR-A chemotherapy regimen and 35 children in the I/HR-B chemotherapy regimen.The median age of 268 children in the middle and later stages of maintenance treatment was 6.32 years,and the median duration was 538.50 days.By the end of December 31,2022,the EFS was 58.94(46.60,74.82)months and OS was 61.22(49.07,76.95)months.2.Incidence of severe infection:During the middle and late stages of maintenance treatment,85 of 268 children developed 114 hospitalized infection cases.The infection rate was 31.7%(85/268).Among the 85 children,33 had severe infection,with a total of 38 cases.The severe infection rate was 12.4%(33/268).94 cases of infection were hospitalized in our hospital,of which 37 cases were severe infection.Among the 33 children with severe infection,19 were male and 14 were female.There were 28 patients with B-ALL and 5 patients with T-ALL.There were 15 children at standard-risk,including 8 children receiving chemotherapy under the LR-A regimen,7 children receiving chemotherapy under the LR-B regimen.18 children were at medium risk,including 14 children receiving chemotherapy under the I/HR-A regimen and 4 children receiving chemotherapy under the I/HR-B regimen.Among 37 cases of severe infection,33 cases were severe pneumonia,and the complications included sepsis,respiratory failure,etc.2 caces were septicemia and 1 case was sepsis.1 case was a focal infection with a high risk of spread.3.Clinical features:Fever was the most common clinical manifestation and the most common initial symptom in ALL children with severe infection.Cough was the second most common clinical manifestation and the second most common initial symptom.Other clinical manifestations included expectoration,runny nose and wheezing.Lung was the most common infection site,with a total of 30 cases,and other pulmonary complicated with central nervous system infection,pulmonary complicated with bloodstream infection,etc.Among the 37 episodes of severe infections,9 episodes were fungal infections,4 episodes were viral infections,3 episodes were Mycoplasma pneumoniae infections,2 episodes were bacterial infections,and the remaining 12 episodes were mixed infections,including bacterial and fungal infections,viral and fungal infections,etc.The pathogens of 7 severe infections were unknown.33 cases of severe infection were improved/cured after treatment,and 4 cases were discharged automatically,of which 2 cases were improved/cured after discharge,and 2 cases died.4.Risk factors:Univariate analysis showed that there were statistical differences in the incidence of in-hospital infection among children with ALL with different risk stratification(χ2=13.764,P<0.001)and chemotherapy regimen groups(χ2=18.320,P<0.001).The incidence of in-hospital infection was higher in children treated with dexamethasone in chemotherapy,and the difference was statistically significant(χ2=5.550,P<0.05).There were statistical differences in the incidence of severe infection among ALL children with different nutritional status(χ2=6.331,P<0.05)and serum albumin levels(x2=8.736,P<0.01).Multivariate analysis showed that risk stratification(OR=7.649,P<0.05)and application of dexamethasone in chemotherapy(OR=1.769,P<0.05)were risk factors for in-hospital infection in children with ALL,and low serum albumin level(OR=4.158,P<0.01)was a risk factor for severe infection.5.Severe infection and prognosis:There were 238 cases of event-free survival and 26 cases of recurrence.7 died of recurrence.2 cases developed second tumor,and 1 of them died.2 cases died of severe infection during the late period of maintenance treatment.Survival analysis showed that severe infection in the middle and late stages of maintenance therapy was not associated with EFS,but was associated with OS in ALL children.Conclusion:1.Children with ALL also had the risk of severe infection during the middle and late period of maintenance treatment,and severe pneumonia is the most common severe infection in children with ALL at this stage.2.Fungi and viruses are important pathogens of severe infections in ALL children during the middle and late period of maintenance treatment.Low albumin level is the risk factor for severe infection in ALL children and nutritional status is related to the occurrence of severe infection at this stage.3.Severe infection in the middle and late stages of maintenance treatment for ALL children can lead to death and reduce their OS. |
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