Invasive fungal infections in patients withcancer/hematologicalmalignanciesBackgroundshigh risk of invasive fungal infections (IFl)and high mortalityearly diagnosis is usually difficult;limited valueofmicroscopyandmycological culturesnonspecificclinicalfeatures;fevermaybeabsentwithcorticosteroidtherapyinvasive diagnostic procedures (e.g. biopsy) are difficult inhighriskpatientsduetocommonthrombocytopeniavarious treatmentsforcancer/HSCT
Invasive fungal infections in patients with cancer/hematological malignancies Backgrounds ●high risk of invasive fungal infections (IFI) and high mortality ●early diagnosis is usually difficult; limited value of microscopy and mycological cultures ●nonspecific clinical features; fever may be absent with corticosteroid therapy ●invasive diagnostic procedures (e.g. biopsy) are difficult in high risk patients due to common thrombocytopenia ●various treatments for cancer/HSCT 6
Patients at risk of invasive fungal diseases
Patients at risk of invasive fungal diseases 7
Timeline of IFl in patients with neutropenia1007No prophylaxis80Aspergillus6040Candida20020401030Duration of neutropenia (days)Prophylaxiswithfluconazole1000Recoveryfromneutropenia80Aspergillus6040°G-CSF20°Candida0201030408Wingard,JR.ClinInfectDis39:S38-43,2004
Timeline of IFI in patients with neutropenia Recovery from neutropenia G-CSF Candida Aspergillus 0 10 20 30 40 20 40 60 80 100 (%) 0 10 20 30 40 20 40 60 80 100 Candida Aspergillus (%) No prophylaxis Duration of neutropenia (days) Wingard, JR. Clin Infect Dis 39 :S38-43, 2004. Prophylaxis with fluconazole 8
Risk factors for invasive aspergillosisANG-patternEnvironmentalFactors4-93HEPAfilterAntigenexposureInfaret shapedconsolidationCavityHalosignAIDSMass likeconsolidationMacrophaeCellularimmunityNeutrophil(T cell)MembranousAIR-patternbarrierOrganfunctionPeribronchialconSolidatiortree-in-bud patternFNHematopoieticstemcelltransplantationpost-GVHD,Steroids,immunosuppressantschemotherapy9
Cellular immunity （T cell） Antigen exposure Macrophage Neutrophil Membranous barrier Organ function Environmental Factors HEPA filter AIDS FN postchemotherapy Hematopoietic stem cell transplantation GVHD , Steroids, immuno suppressants Risk factors for invasive aspergillosis 9
MadhdF1?E16,26188S288648ExecutiveSummaryofJapaneseDomesticGuidelinesforRiskstraficationaccordingtotheprobabilityofIFlManagementofDeep-seatedMycosis2014ProphylacticantifungalsareChairman: Shigeru KohnoCommiueemembers Kazuo Tamura',YoshihitoNiki',Koichi Izumikawa'Shinichi OkaKenji Ogawa,Junichi Kadota,KatsuhikoKamel,Yoshinobu KandaTetsuya KiuchiconsideredinpatientswithKazutoshi Shibuya,Syunji TakakuraToruTakata,YoshioTakesue",Katsuji TerIssei TokimatsuTakahiroFukuda,Shigefumi Maesaki',KoichiMakimuramorethanintermediate-riskHiroshigeMikamo",KotarouMitsutakeYoshitsuguMiyazaki"Masaaki MAkira Yasuoka',Keiko Yano',Noboru Yamanaka',and Minoru Yoshid.I.Assessmentofriskfactors.Theriskof invasivefungal diseaseisassessedaccordingtounderlyingdisease,typeoftreatment,etcHigh-risk groupIntermediate-risk groupLow-risk groupAntifungal prophylaxis isAntifungalprophylaxisisAntifungalprophylaxisisnotrecommended.consideredrecommended.Chart Ill:Indications for→Chart Ill:Indicationsfor+ Expectedduration ofantifungalprophylaxisantifungalprophylaxisneutropenia(<500/μL)forlessthan7days口口ConsolidationtherapyforRemissioninductiontherapyfor Nohigh/intermediateriskacute leukemia [acute myeloidacuteleukemiafactorsAutologousHSCTleukemia(AML),acutelymphoblasticleukemia(ALL)）(particularlywith mucosaldamage)myelodysplasticsyndrome Prolonged use of(MDS)口Allogeneichematopoieticstemcorticosteroids(0.3mg/kg.Idayofprednisolonecelltransplantation(HSCT)口Grade Il-IVacuteequivalent,for3weeksorgraft-versus-hostdiseaselonger,high-dose(GVHD).chronicGVHDdexamethasonefor(+corticosteroidtherapy)myeloma,etc...)口Expecteddurationof Treatmentwithotherneutropenia(<500/μL)for10recognizedTcelldays or longer.immunosuppressants,suchas cyclosporine, TNF-ablockers,specificmonoclonalantibodiesornucleosideanaloguesduringthepast 90daysExpecteddurationof10neutropenia(<500/μL)for7-10days
Risk strafication according to the probability of IFIk Prophylactic antifungals are considered in patients with more than intermediate-risk. 10