Impact of treatment intensity on infectious complications in patients with acute myeloid leukemia

Impact of treatment intensity on infectious complications in patients with acute myeloid leukemia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of treatment intensity on infectious complications in patients with acute myeloid leukemia Sebastian Scholl, Romy Tober, Ulf Schnetzke, Maximilian Fleischmann, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1378367/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background: Infectious complications reflect a major challenge in the treatment of patients with acute myeloid leukemia (AML). Both induction chemotherapy and epigenetic treatment with hypomethylating agents (HMA) are associated with severe infections while neutropenia represents a common risk factor. Here, 220 consecutive and newly diagnosed AML patients were analyzed with respect to infectious complications dependent on treatment intensity and antifungal prophylaxis applied to these patients. Patients and Methods: We retrospectively analyzed 220 patients with newly diagnosed AML at a tertiary care hospital between August 2016 and December 2020. The median age of AML patients undergoing induction chemotherapy (n=102) was 61 years (25-76 years). Patients receiving palliative AML treatment (n=118) had a median age of 75 years (53-91 years). We assessed the occurrence of infectious complication including the classification of pulmonary invasive fungal disease (IFD) according to the EORTC/MSG criteria at diagnosis and until day 100 after initiation of AML treatment. Furthermore, admission to intensive care unit (ICU) and subsequent outcome was analyzed for both groups of AML patients, respectively. Results: AML patients subsequently allocated to palliative AML treatment have a significantly higher risk of pneumonia at diagnosis compared to patients undergoing induction chemotherapy (37.3% vs. 13.7%, P <0.001) including a higher probability of atypical pneumonia (22.0% vs. 10.8%, P =0.026). Furthermore, urinary tract infections are more frequent in the palliative subgroup at the time of AML diagnosis (5.1% vs. 0%, P =0.021). Surprisingly, the incidence of pulmonary IFD is significantly lower after initiation of palliative AML treatment compared to the occurrence after induction chemotherapy (8.4% vs. 33.3%, P <0.001) despite only few patients of the palliative treatment group received Aspergillus spp. -directed antifungal prophylaxis. The overall risk for infectious complications at AML diagnosis is significantly higher for palliative AML patients at diagnosis while patients undergoing induction chemotherapy have a significantly higher risk of infections after initiation of AML treatment. In addition, there is a strong correlation between the occurrence of pneumonia including atypical pneumonia and pulmonary IFD and the ECOG performance status at diagnosis in the palliative AML patient group. Analysis of intensive care unit (ICU) treatment (e.g. in case of sepsis or pneumonia) for both subgroups reveals a positive outcome in 10 of 15 patients (66.7%) with palliative AML treatment and in 15 of 18 patients (83.3%) receiving induction chemotherapy. Importantly, the presence of infections and the ECOG performance status at diagnosis significantly correlate with the overall survival (OS) of palliative AML patients (315 days w/o infection vs. 69 days with infection, P 0.0049 and 353 days for ECOG 2, P <0.001, respectively) in this intent-to-treat analysis. Conclusion: The risk and the pattern of infectious complications at diagnosis and after initiation of AML therapy depends on age, ECOG performance status and subsequent treatment intensity. A comprehensive diagnostic work-up for identification of pulmonary IFD is indispensable for effective treatment of pneumonia in AML patients. The presence of infectious complications at diagnosis contributes to an inferior outcome in elderly AML patients. AML infections epigenetic therapy induction chemotherapy IFD pneumonia Figures Figure 1 Figure 2 Full Text Supplementary Files 20220220SupplementFigureS1.pptx Figure S1: CONSORT diagram of AML patients (n=118) with palliative treatment. Illustration of antecedent hematological disease or specific therapy prior to diagnosis of AML and distribution of firstline AML therapy in patients allocated to palliative AML treatment. 20220220SupplementFigureS2.pptx Figure S2: CONSORT diagram of AML patients (n=102) with induction chemotherapy. Overview of antecedent hematological disease or specific therapy prior to diagnosis of AML, distribution of hematological response and subsequent treatment of patients undergoing induction chemotherapy as first-line treatment of AML. 20220220SupplementFigureS3.pptx Figure S3: Spectrum of pathogens obtained from blood culture samples dependent on AML treatment intensity. Distribution of positive blood culture specimens indicating the spectrum of isolated bacteria in febrile patients after palliative AML treatment (A) or following induction chemotherapy (B). Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 23 Feb, 2022 Reviewers invited by journal 22 Feb, 2022 Editor assigned by journal 22 Feb, 2022 First submitted to journal 20 Feb, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1378367","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":85666958,"identity":"5c1d7f35-94a3-479e-baec-a476eb68b7a0","order_by":0,"name":"Sebastian 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Hospital: Universitatsklinikum Jena","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anita","middleName":"","lastName":"Glaser","suffix":""},{"id":85666956,"identity":"2666fd94-74b8-4a07-af03-d82f930358f4","order_by":8,"name":"Christian Thiede","email":"","orcid":"","institution":"Dresden University Hospital: Universitatsklinikum Carl Gustav Carus","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Christian","middleName":"","lastName":"Thiede","suffix":""},{"id":85666957,"identity":"04888143-ece4-448c-a6c8-204816fca3a3","order_by":9,"name":"Andreas Hochhaus","email":"","orcid":"","institution":"Jena University Hospital: Universitatsklinikum Jena","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Andreas","middleName":"","lastName":"Hochhaus","suffix":""}],"badges":[],"createdAt":"2022-02-20 14:07:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1378367/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1378367/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":18574289,"identity":"4db06728-6fde-4319-809e-e5964049c52a","added_by":"auto","created_at":"2022-02-24 15:54:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36896,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT diagram of time-dependent pneumonia subtypes for both patient groups. Distribution of absolute numbers of patients presenting with pneumonia either at the time of AML diagnosis (upper part) or after initiation of AML therapy (lower part) for patients allocated to palliative AML treatment (left) or induction chemotherapy (right).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-1378367/v1/0920b264bfc601cfed22468c.png"},{"id":18574293,"identity":"4a8d28a0-1acb-4bc0-9f62-1120633d8711","added_by":"auto","created_at":"2022-02-24 15:54:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":95751,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier estimates for overall survival (OS) dependent on the ECOG performance score (A) or on the modified Charlson comorbidity index (B) for AML patients undergoing palliative treatment.\u0026nbsp;\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-1378367/v1/cc36c94031a37ff42901d1e5.png"},{"id":18575182,"identity":"a9615341-d7d2-4173-a7a9-1e7d11291f69","added_by":"auto","created_at":"2022-02-24 16:00:18","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":532876,"visible":true,"origin":"","legend":"","description":"","filename":"20220220ManuskriptInfectionsAMLScholl.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1378367/v1_covered.pdf"},{"id":18574290,"identity":"4178a393-4adf-4cb5-abcd-9f29dbeddaa0","added_by":"auto","created_at":"2022-02-24 15:54:11","extension":"pptx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":199943,"visible":true,"origin":"","legend":"\u003cp\u003eFigure S1: CONSORT diagram of AML patients (n=118) with palliative treatment. Illustration of antecedent hematological disease or specific therapy prior to diagnosis of AML and distribution of first\u0002line AML therapy in patients allocated to palliative AML treatment.\u0026nbsp;\u003c/p\u003e","description":"","filename":"20220220SupplementFigureS1.pptx","url":"https://assets-eu.researchsquare.com/files/rs-1378367/v1/f0098c829f02411297fae2e5.pptx"},{"id":18574910,"identity":"779d379d-27f1-4ac9-8f38-e8c2e6251a51","added_by":"auto","created_at":"2022-02-24 15:57:11","extension":"pptx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":45471,"visible":true,"origin":"","legend":"\u003cp\u003eFigure S2: CONSORT diagram of AML patients (n=102) with induction chemotherapy. Overview of antecedent hematological disease or specific therapy prior to diagnosis of AML, distribution of hematological response and subsequent treatment of patients undergoing induction chemotherapy as first-line treatment of AML.\u0026nbsp;\u003c/p\u003e","description":"","filename":"20220220SupplementFigureS2.pptx","url":"https://assets-eu.researchsquare.com/files/rs-1378367/v1/c6cbe47a40d02fed3668bdba.pptx"},{"id":18575181,"identity":"8db51e5c-2802-447f-8177-2631b7669bd8","added_by":"auto","created_at":"2022-02-24 16:00:12","extension":"pptx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":56284,"visible":true,"origin":"","legend":"\u003cp\u003eFigure S3: Spectrum of pathogens obtained from blood culture samples dependent on AML treatment intensity. Distribution of positive blood culture specimens indicating the spectrum of isolated bacteria in febrile patients after palliative AML treatment (A) or following induction chemotherapy (B).\u003c/p\u003e","description":"","filename":"20220220SupplementFigureS3.pptx","url":"https://assets-eu.researchsquare.com/files/rs-1378367/v1/86b6c9d8f17b3cd33448b4b2.pptx"}],"financialInterests":"","formattedTitle":"Impact of treatment intensity on infectious complications in patients with acute myeloid leukemia","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-1378367/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-cancer-research-and-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocr","sideBox":"Learn more about [Journal of Cancer Research and Clinical Oncology](https://www.springer.com/journal/432)","snPcode":"432","submissionUrl":"https://submission.nature.com/new-submission/432/3","title":"Journal of Cancer Research and Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"AML, infections, epigenetic therapy, induction chemotherapy, IFD, pneumonia","lastPublishedDoi":"10.21203/rs.3.rs-1378367/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1378367/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Infectious complications reflect a major challenge in the treatment of patients with acute myeloid leukemia (AML). Both induction chemotherapy and epigenetic treatment with hypomethylating agents (HMA) are associated with severe infections while neutropenia represents a common risk factor. Here, 220 consecutive and newly diagnosed AML patients were analyzed with respect to infectious complications dependent on treatment intensity and antifungal prophylaxis applied to these patients. \u003c/p\u003e\u003cp\u003ePatients and Methods: We retrospectively analyzed 220 patients with newly diagnosed AML at a tertiary care hospital between August 2016 and December 2020. The median age of AML patients undergoing induction chemotherapy (n=102) was 61 years (25-76 years). Patients receiving palliative AML treatment (n=118) had a median age of 75 years (53-91 years). We assessed the occurrence of infectious complication including the classification of pulmonary invasive fungal disease (IFD) according to the EORTC/MSG criteria at diagnosis and until day 100 after initiation of AML treatment. Furthermore, admission to intensive care unit (ICU) and subsequent outcome was analyzed for both groups of AML patients, respectively. \u003c/p\u003e\u003cp\u003eResults: AML patients subsequently allocated to palliative AML treatment have a significantly higher risk of pneumonia at diagnosis compared to patients undergoing induction chemotherapy (37.3% vs. 13.7%, P \u0026lt;0.001) including a higher probability of atypical pneumonia (22.0% vs. 10.8%, P =0.026). Furthermore, urinary tract infections are more frequent in the palliative subgroup at the time of AML diagnosis (5.1% vs. 0%, P =0.021). Surprisingly, the incidence of pulmonary IFD is significantly lower after initiation of palliative AML treatment compared to the occurrence after induction chemotherapy (8.4% vs. 33.3%, P \u0026lt;0.001) despite only few patients of the palliative treatment group received Aspergillus spp. -directed antifungal prophylaxis. The overall risk for infectious complications at AML diagnosis is significantly higher for palliative AML patients at diagnosis while patients undergoing induction chemotherapy have a significantly higher risk of infections after initiation of AML treatment. In addition, there is a strong correlation between the occurrence of pneumonia including atypical pneumonia and pulmonary IFD and the ECOG performance status at diagnosis in the palliative AML patient group. Analysis of intensive care unit (ICU) treatment (e.g. in case of sepsis or pneumonia) for both subgroups reveals a positive outcome in 10 of 15 patients (66.7%) with palliative AML treatment and in 15 of 18 patients (83.3%) receiving induction chemotherapy. Importantly, the presence of infections and the ECOG performance status at diagnosis significantly correlate with the overall survival (OS) of palliative AML patients (315 days w/o infection vs. 69 days with infection, P 0.0049 and 353 days for ECOG \u0026lt; 1 vs. 50 days for ECOG \u0026gt; 2, P \u0026lt;0.001, respectively) in this intent-to-treat analysis. \u003c/p\u003e\u003cp\u003eConclusion: The risk and the pattern of infectious complications at diagnosis and after initiation of AML therapy depends on age, ECOG performance status and subsequent treatment intensity. A comprehensive diagnostic work-up for identification of pulmonary IFD is indispensable for effective treatment of pneumonia in AML patients. The presence of infectious complications at diagnosis contributes to an inferior outcome in elderly AML patients.\u003c/p\u003e","manuscriptTitle":"Impact of treatment intensity on infectious complications in patients with acute myeloid leukemia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-02-24 15:54:10","doi":"10.21203/rs.3.rs-1378367/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2022-02-23T20:37:11+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-02-22T09:51:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-02-22T08:19:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cancer Research and Clinical Oncology","date":"2022-02-20T09:06:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cancer-research-and-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocr","sideBox":"Learn more about [Journal of Cancer Research and Clinical Oncology](https://www.springer.com/journal/432)","snPcode":"432","submissionUrl":"https://submission.nature.com/new-submission/432/3","title":"Journal of Cancer Research and Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"deb8cae2-3c84-4db9-86fa-073d891ffd29","owner":[],"postedDate":"February 24th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-03-23T16:47:50+00:00","versionOfRecord":[],"versionCreatedAt":"2022-02-24 15:54:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1378367","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1378367","identity":"rs-1378367","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}