Correlation Analysis Between Infection During VDLP Chemotherapy And Disease Prognosis In Children With Acute Lymphoblastic Leukemia

ObjectiveOur study aimd to collect and analyze the clinical characteristics of children with acute lymphoblastic leukemia(ALL)at initial diagnosis,infection during VDLP chemotherapy,treatment effect and prognosis.1)To investigate the main clinical features of children with ALL,2)to explore the risk factors of infection,3)to follow up and analyze the outcome and prognosis of children,4)and to provide reference for clinical diagnosis and treatment.In order to make medical workers pay attention to differential diagnosis in the process of treatment,improve the diagnostic rate,reduce the occurrence of adverse reactions of chemotherapy,ensure the continuity and integrity of chemotherapy,improve the survival rate,so as to reduce the psychological pressure and economic burden of children and their families.MethodThe clinical data of 337 children with newly diagnosed acute lymphoblastic leukemia admitted to the Department of Pediatrics,Qilu Hospital of Shandong University from January 2015 to December 31 2019 were retrospectively analyzed.All children were treated with CCCG-ALL-2015 regimen.The clinical characteristics of the children at initial diagnosis were analyzed,including gender,age,White blood cell(WBC)count at initial diagnosis,time from symptom onset to initial diagnosis,and symptoms at initial diagnosis.The occurrence of infection during VDLP chemotherapy,the site and severity of infection,pathogen and drug sensitivity results,treatment plan,whether it affects subsequent chemotherapy and disease prognosis were analyzed.According to different data types,corresponding methods were used for statistical analysis to explore the infection-related factors and prognostic factors of ALL in children.P<0.05 was considered statistically significant.Results1.Clinical characteristics at initial diagnosis:a total of 337 children were enrolled,including 205 males and 132 females,with a male to female ratio of 1.55:1.They were divided into low-risk 199 cases(59.05%),intermediate-risk 132 cases(39.17%),and high-risk 6 cases(1.78%)according to age,auxiliary examination and treatment effect.Fever(76.26%)was the most common symptom at initial diagnosis,followed by infection(38.28%),anemia(33.23%),bone and joint pain(22.26%),and bleeding(20.18%).The diagnosis was confirmed quickly in children with typical symptoms at the time of initial diagnosis,and the rate of misdiagnosis and underdiagnosis was low,while the rate of misdiagnosis and underdiagnosis was highest in children with infiltrative bone and joint manifestations.2.Analysis of infections associated with the chemotherapy phase of VDLP:(1)Rate and site of infection:A total of 259 infections occurred in 237 of the 337 children,representing an infection rate of 70.33%.The most common infection was respiratory tract infection,followed by fever of unknown origin,rare infections included intracranial infection and pancreatitis.(2)Analysis of the distribution of pathogens and drug resistance:A total of 65 strains of pathogenic bacteria,39 strains of G+bacteria(60%),17 strains of G-bacteria(26.15%),5 strains of fungi(7.69%),4 cases of virus(6.15%)were detected.The positive rate was highest in blood culture and lowest in cerebrospinal fluid culture.G+bacteria were mainly Staphylococcus,Enterococcus and Streptococcus.The sensitivity of G+bacteria to Vancomycin and Linezolid was 100%,the sensitivity to Quinolone antibiotics was more than 90%,and the resistance rate to penicillin G and ceftriaxone was the highest.G-bacteria with Pseudomonas aeruginosa and Escherichia coli as the main species,G-bacteria were 100%sensitive to amikacin,while the resistance rate to cotrimoxazole and ceftriaxone reached 79%;5 cases of Candida tropicalis were sensitive to antifungal drugs.(3)Analysis of infection-related factors:The results of both univariate and multifactorial analyses showed statistically significant differences(P<0.05)between infection and time from symptom onset to diagnosis(≤15d or>15d),duration of granular deficiency(≥15d or<15d),and whether protective isolation was given in laminar beds.(4)Severity of infection:Among 337 children,100 were mildly infected(29.67%),138 were severely infected(40.95%),and 99 were not infected(29.38%).The number of days of laminar beds use,PCT level and duration of neutropenia were significantly higher in the severely infected group than in the non-severely infected group(P<0.001),the neutrophil count was lower than in the other two groups(P=0.036),and the CRP level was not statistically different(P>0.05).(5)Therapeutic effect:Among 337 children,328 successfully completed VDLP chemotherapy,and 326 successfully received the next stage of chemotherapy.7 cases died during VDLP chemotherapy,all of which were complicated with grade 4 or above infection.2 cases died after forced termination of chemotherapy,and 2 cases died after completion of VDLP chemotherapy.3.Disease prognosis and regression:By the end of 2022,45 of 337 patients had relapsed,with a recurrence rate of 13.35%,including 31 patients with bone marrow recurrence,7 patients with testicular recurrence,7 patients with central recurrence,and 11 patients receiving transplantation after recurrence.3 cases were complicated with second tumor.The results of univariate analysis showed that female,age<1 year,T-ALL,initial WBC count≥50×109/L,fusion gene KMT2A-r rearrangement,co-infection during VDLP chemotherapy,non-conversion of D19 MRD,and high risk were risk factors associated with mortality(P<0.05),with gender(P=0.037),initial WBC count(P=0.007),infection during chemotherapy for VDLP(P=0.042),and risk level(P=0.006)were independent risk factors for mortality in children,with relative risk levels and 95%confidence intervals of 2.145(1.046,4.398),3.072(1.350,6.993),2.567(1.033,6.379),3.061(1.379,6.797).Survival analysis and comparison of survival rates revealed statistical differences between groups in gender,age,immunophenotype,initial WBC count,fusion gene,whether VDLP was infected,whether D19 MRD turned negative,and risk level(P<0.05).Conclusions1.ALL children whose first symptom is only joint pain have the highest rate of clinical misdiagnosis and underdiagnosis.The incidence of infection during VDLP chemotherapy is high in children with the time from symptom onset to diagnosis more than 15 days.2.Respiratory tract infections are most common during chemotherapy for VDLP,and the pathogens are predominantly G+bacteria.The longer the neutrophil deficiency,the more severe the infection,and giving protective isolation in a laminar bed can reduce the occurrence of severe infections.3.Female,age<1 year,T-ALL,initial WBC count ≥50×109/L,fusion gene KMT2A-r rearrangement,co-infection during VDLP chemotherapy,non-conversion of D19 MRD,and high-risk ALL were associated with high mortality(P<0.05).And female,initial WBC count≥50×109/L,co-infection during VDLP chemotherapy,and high-risk ALL could be independent predictors of mortality.