Clinical Analysis Of Acute Leukemia Patients With Invasive Fungal Infections

Part 1 Primary antifungal prophylaxis of invasive fungal diseases in acute leukemia patientsObjective1.Evaluate the implementation of primary antifungal prophylaxis(PAP)during the initial remission induction of acute leukemia patients in our hospital.2.Analyze the risk factors of invasive fungal diseases(IFD)in acute leukemia patients.3.Investigate the breakthrough IFD and the empirical therapy of different antifungal drugs to provide some reference for clinicians.MethodThis was a retrospective observational single-center study,including non-M3 acute myeloid leukemia(AML)?acute lymphocytic leukemia(ALL)and mixed phenotype acute leukemia(ABL)patients receiving initial remission induction chemotherapy from January 2016 to June 2018 in our hospital.A total of 493 patients with no clinical signs of infection(eg,fever,lung inflammation,etc.)were selected for admission.Separate patients into IFD positive group(proven and probable)and IFD negative group(possible and unconfirmed)to evaluate the effective of primary antifungal prophylaxis(PAP)in patients with AL.Analyze the use of antifungal drugs and the effectiveness of their preventive treatment.Result1?From January 2016 to June 2018,a total of 842 AL patients with initial remission induction chemotherapy in our hospital,82 cases were diagnosed IFD(proven and probable),the total incidence of IFD was 9.74%,AML patients with the IFD was significantly higher than that of ALL patients(11.74%vs 5.78%,P=0.009)and similar to ABL(11.74%vs 10%,P=1).2?Of the 493 patients who had no symptoms of infection at admission,377(76.47%,377/493)were given primary antifungal prophylaxis(PAP),and 116(23.53%,116/493)did not.The incidence of IFD(proven and probable)in the PAP group was 3.18%,which was significantly lower than that in the non-PAP group(7.76%)(P=0.039<0.05).There was no significant difference in the breakthrough IFD rate of PAP before induction chemotherapy,during chemotherapy or after chemotherapy(4%vs 3.17%vs 3.23%,P=0.612)?The incidence of IFD was higher in patients whose PAP began at neutrophils were less than or equal to 1*10^9 that that more than 1*10^9(4.4%vs 0.79%),but P=0.067>0.05,the difference was not statistically significant.3?The factors influencing the incidence of IFD in patients with AL were age,AML,infections at admission,empirical antifungal therapy,antibiotics,neutropenia,no complete remission after chemotherapy,and PAP,of which only PAP was a protective factor for IFD in patients with AL(OR:0.391,95%CI 0.160-0.952,P=0.001),and the rest are risk factors for IFD.4?72.15%cases were voriconazole and 27.85%was the other antifungal drugs.The incidence of bIFD in voriconazole is 2.77%and 4%in other(P=0.127),the difference was not significant.The rate of empirical antifungal therapy in voriconazole was significantly lower than the other drugs(13.04%vs 31%,P<0.001).ConclusionThe total incidence of IFD in AL patients with initial remission induction chemotherapy was 9.74%,and there were still 23.53%patients without PAP.The risk factors of IFD in our study were age?AML?infections at admission,empirical antifungal therapy,antibiotics,neutropenia and no complete remission after chemotherapy.More than 70%patients received voriconazole as PAP in our study,and the breakthrough IFD was similar to other drugs,but the rate of empirical antifungal therapy was lower.Part 2 Empiric antifungal therapy of invasive fungal diseases in acute leukemia patientsObjective1.Evaluate the implementation of empiric antifungal therapy(EAT)during the initial remission induction of acute leukemia patients in our hospital.2.Analyze the risk factors of invasive fungal diseases(IFD)in acute leukemia patients with infections.3.Investigate the efficacy and safety of voriconazole in empiric antifungal therapy.MethodA total of 349 patients with clinical signs of infection(eg,fever,lung inflammation,etc.)were selected for admission.Separate patients into IFD positive group(proven and probable)and IFD negative group(possible and unconfirmed)to evaluate the effective of empiric antifungal therapy(EAT)in patients with AL.Result1?A total of 349 patients with infection symptoms were admitted,and the incidence of IFD was 17.48%.There were 274 patients with EAT and 75 without EAT.The incidence of IFD was 14.96%and 26.67%,respectively.The incidence of IFD without EAT was significantly higher than that of EAT(P=0.025<0.05).EAT can significantly reduce the incidence of IFD in patients with symptoms of infection at admission.2?Risk factors for IFD in patients with acute leukemia admitted to hospital were analyzed by multivariate logistic regression:age,neutropenia,diagnosis-driven therapy,antibiotics,and remission after chemotherapy.In addition,the incidence of IFD before the start of chemotherapy(19.59%)was significantly higher than that during chemotherapy(10.53%)(P=0.043<0.05),suggesting that patients with concomitant infections on admission should be treated best during chemotherapy.3?The highest use of antifungal drugs in our hospital was voriconazole with 82.22%.The incidence of IFD under voriconazole was 15.6%,and the incidence of adverse events was 4.5%.Voriconazole is effective and safety in empiric antifungal therapy.ConclusionThere were also 21.49%patients with infections at admission without EAT in our hospital.We used voriconazole in EAT most,and it was effective and safety in empiric antifungal therapy.Part 3 Diagnostic Value of G and GM test in Acute Leukemia Patients with Invasive Fungal DiseaseObjectiveTo analysis the diagnostic value of(1,3)-beta-D-glucan and galactomannan in acute leukemia patients with invasive fungal disease,and explore the application features of serological detection(G/GM)and lung CT for early diagnosis of invasive fungal disease.MethodsA total of patients with acute leukemia in the department of hematology of our hospital from June 2016 to December 2016 with high risk invasive fungal infections were enrolled.According to the diagnostic criteria of IFD,they were divided into IFD confirmed group(including confirmed and clinically diagnosed cases,62 cases)and IFD unconfirmed group(suspected IFD and non-IFD,431 cases).We compared the results of(1,3)-beta-D-glucan and galactomannan in these two groups,and evaluated the early diagnostic value in IFD with combined two tests.In addition,we selected 26 serology positive patients with negative lung CT results at admission and positive during hospitalization to compare whose positive result comes earlier between serological detection and CT.ResultsThe positive rate of(1,3)-beta-D-glucan in IFD confirmed group and IFD unconfirmed group was 56.5%and 10.4%,meanwhile,those of galactomannan test were 41.9%and 9.0%respectively.The sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of(1,3)-beta-D-glucan were 56%,90%,44%and 92%,and galactomannan were 42%?91%?40%and 93%,respectively.Moreover,the combination of the(1,3)-beta-D-glucan and galactomannan can improve sensitivity to 69%or specificity to 98%.The positive results of serological detection(G/GM)come earlier than CT changes for five days approximately.Conclusion(1,3)-beta-D-glucan and galactomannan test both have high sensitivity and specificity,and the combination of them can improve the diagnostic efficacy and guide the clinical antifungal therapy more precisely.In the early clinical diagnosis of IFD,the positive results of serological detection come earlier than lung CT.