Study On The Risk Factors Of Invasive Fungal Disease And Early Empirical Antifungal Strategy In Children With Acute Leukemia

Part 1 Incidence and Risk Factors of Invasive Fungal Disease in Children with Acute LeukemiaObjectiveThe clinical data of children with acute leukemia hospitalized in children’s medical center in Qilu Hospital of Shandong University were collected to study the incidence and risk factors of invasive fungal disease(IFD)in acute leukemia children with febrile neutropenia to provide reference for clinical work.MethodsThis was a retrospective study.The clinical data of children with acute leukemia hospitalized in children’s medical center in Qilu Hospital of Shandong University from January 2018 to December 2021 were collected.The incidence of IFD was investigated,and cases were divided into observation group or control group according to whether they developed IFD.Those risk factors that were statistically significant in univariate logistic regression were included in multivariate logistic regression to identify the independent risk factors of IFD.ResultsIn this part of the study,220 cases were included.There were 20 cases diagnosed with IFD(observation group)and 200 cases without IFD(control group).The incidence of IFD was 20/220(9.1%).Univariate logistic regression indicated that duration of neutropenia(OR=1.065),95%CI 1.005-1.129,P=0.033)and patchy shadows/nodules/ground-glass opacities in the first chest CT after fever(OR=5.211,95%CI 2.017-13.461,P=0.001)were risk factors of IFD,and multivariate logistic regression analysis indicated that duration of neutropenia(OR=1.078,95%CI 1.013-1.147,P=0.018)and patchy shadows/nodules/ground-glass opacities in the first chest CT after fever(OR=5.893,95%CI 2.202-15.772,P<0.001)were independent risk factors of IFD.ConclusionFor acute leukemia children with febrile neutropenia,prolonged duration of neutropenia and patchy shadows/nodules/ground-glass opacities in the first chest CT after fever are independent risk factors of IFD.Part 2 Effectiveness of Early Empirical Antifungal Strategy in Children with Acute LeukemiaObjectiveThe clinical data of children with acute leukemia hospitalized in children’s medical center in Qilu Hospital of Shandong University were collected to explore the effectiveness,economy and safety of early empirical antifungal strategy in acute leukemia children with febrile neutropenia to provide reference for reasonable clinical decisions.MethodsThis was a retrospective study.The clinical data of children with acute leukemia hospitalized in children’s medical center in Qilu Hospital of Shandong University from January 2018 to December 2021 were collected.Cases were divided into early group or control group according to whether they were given empirical antifungal therapy before the fourth day of fever.Cases of acute lymphoblastic leukemia(ALL)and acute myeloid leukemia(AML)were discussed respectively.The main outcomes included incidence of IFD and time to stable defervescence.The second outcomes were incidence of severe pneumonia,exposure time of antifungal agents,cost of antifungal agents,infection-related hospitalization time and adverse reactions of antifungal agents.ResultsIn this part of the study,188 cases were included and there were 127 cases of ALL and 61 cases of AML.In cases of ALL,there were 34 cases in early group and 93 cases in control group.Propensity score matching was adopted to balance the differences of baseline data in these two groups.A total of 78 cases were included after propensity score matching and there were 30 cases in early group and 48 cases in control group.There were no significant differences of incidence of IFD(16.7%vs.16.7%,P=1.000)and time to stable defervescence[6(3,6)days vs.6(3,8)days,P=0.616]between the two groups.There were no significant differences of incidence of severe pneumonia between the two groups(6.7%vs.10.4%,P=0.876).Exposure time of antifungal agents was longer in early group than that in control group[8(5,11)days vs.0(0,7)days,P=0.001].Antifungal agents’cost was higher in early group than that in control group[7718.92(3173.60,11022.75)yuan vs.0.00(0.00,4965.60)yuan,P<0.001].There was no statistical difference in infection-related hospitalization time between the two groups[14(8,20)days vs.11(8,15)days,P=0.200].A case of voriconazole-induced severe liver enzymes elevation was observed in early group.In cases of AML,there were 30 cases in early group and 31 cases in control group.Baseline data were balanced between these two groups.There were no significant differences of incidence of IFD(0.0%vs.3.2%,P=1.000)and time to stable defervescence[5(4,6)days vs.6(4,7)days,P=0.672]between the two groups.There were no significant differences of incidence of severe pneumonia between the two groups(3.3%vs.12.9%,P=0.371).Exposure time of antifungal agents was longer in early group than that in control group[9(6,11)days vs.0(0,7)days,P<0.001].Antifungal agents’ cost was higher in early group than that in control group[5532.65(4662.99,8324.59)yuan vs.0.00(0.00,2856.24)yuan,P<0.001].Infection-related hospitalization time was longer in early group than that in control group[16(12,23)days vs.11(9,17)days,P=0.016].There were no antifungal agents-related adverse reactions in both groups.Conclusion1.For acute leukemia children with febrile neutropenia,the available evidence is insufficient to support the initiation of an early empirical antifungal strategy(within 4 days of fever).2.Pediatricians should decide when to initiate empirical antifungal therapy after evaluating willingness and compliance of children and their families,on the basis of balancing effectiveness and adverse reactions of antifungal agents.