From Unexplained Fever to a Second Malignancy: Peripheral T-cell Lymphoma Following Long-term Olaparib Maintenance Therapy in Ovarian Cancer

From Unexplained Fever to a Second Malignancy: Peripheral T-cell Lymphoma Following Long-term Olaparib Maintenance Therapy in Ovarian Cancer | 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 Case Report From Unexplained Fever to a Second Malignancy: Peripheral T-cell Lymphoma Following Long-term Olaparib Maintenance Therapy in Ovarian Cancer Juanjuan Cai, Yuan Chen, Wanmao Ni, Yirui Chen, Yining Dai This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8684567/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Fever of unknown origin (FUO) presents a common clinical challenge, with lymphoma being a significant neoplastic cause. Olaparib, a cornerstone in ovarian cancer maintenance therapy, has well-documented hematologic toxicities. However, its potential association with peripheral T-cell lymphoma (PTCL) remains unreported. Case Presentation: We report the case of a 77-year-old woman with advanced ovarian cancer on long-term maintenance therapy with olaparib and letrozole for over three years, who presented with fever and progressive cytopenia. Comprehensive infectious and rheumatologic workups were negative. Cell-free DNA sequencing revealed complex chromosomal abnormalities. 18 FDG PET/CT showed diffuse, intense skeletal hypermetabolism (SUVmax 16.0). Subsequently laboratory findings, including extreme hyperferritinemia (> 33511.2 ng/mL), elevated sIL-2R, hypertriglyceridemia, and hypofibrinogenemia, fulfilled the criteria for hemophagocytic lymphohistiocytosis (HLH). Bone marrow biopsy ultimately confirmed the diagnosis of peripheral T-cell lymphoma (PTCL) with marrow involvement. Despite discontinuing olaparib and initiating therapy for HLH and lymphoma, the patient's condition deteriorated rapidly, leading to death within one month of admission. Conclusion The case represents the first reported temporal association between long-term olaparib therapy and the development of PTCL in an ovarian cancer patient. It underscores the importance of considering secondary hematologic malignancies, including lymphoma, in patients on novel targeted therapies who present with unexplained FUO and cytopenias. fever of unknown origin cytopenia peripheral T-cell lymphoma hemophagocytic lymphohistiocytosis Olaparib ovarian cancer Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-8684567","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":591490065,"identity":"8ce0307f-2595-4b10-97b9-6ade9ef63226","order_by":0,"name":"Juanjuan Cai","email":"","orcid":"","institution":"Zhejiang Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Juanjuan","middleName":"","lastName":"Cai","suffix":""},{"id":591490066,"identity":"8e52c2b3-0925-4f0e-9b49-57e59391c691","order_by":1,"name":"Yuan Chen","email":"","orcid":"","institution":"Zhejiang Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Chen","suffix":""},{"id":591490067,"identity":"e1204d13-fe5b-4535-b3ac-9dd0a8ec0ba8","order_by":2,"name":"Wanmao Ni","email":"","orcid":"","institution":"Zhejiang Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wanmao","middleName":"","lastName":"Ni","suffix":""},{"id":591490071,"identity":"d32a2151-800c-42ef-824c-ab969a9a77e7","order_by":3,"name":"Yirui Chen","email":"","orcid":"","institution":"Zhejiang Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yirui","middleName":"","lastName":"Chen","suffix":""},{"id":591490076,"identity":"86b6ccd8-cd61-49af-b06e-59822b7b76b8","order_by":4,"name":"Yining Dai","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYDCCA4wNDAwVDMwgtgQJWs6QpgWIGdsgbOK08B0/3CZdOK+O3eAA88HbPAx2eQS1SJ5JbJOeuY2N2eAAW7I1D0NyMUEtBgeAWni38QC18JhJ8zAcSGwgqOX8Q6CWORJALfzfiNRyA2RLgwHIFjbitEjeeNhszXMsgVnyMJux5RyDZMJa+M6nP7zNU1OXzHe8+eGNNxV2hLUAAQsoOpIhkWlAhHogYP4AJOyIUzsKRsEoGAUjEgAAAtM3fJEoLSsAAAAASUVORK5CYII=","orcid":"","institution":"Zhejiang Provincial People's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yining","middleName":"","lastName":"Dai","suffix":""}],"badges":[],"createdAt":"2026-01-24 07:23:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8684567/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8684567/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104439202,"identity":"50233cf6-7dc9-4a64-bdba-0f28e330be8e","added_by":"auto","created_at":"2026-03-11 17:41:07","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1488729,"visible":true,"origin":"","legend":"","description":"","filename":"manuscriptannhem.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8684567/v1_covered_f348b335-6826-4371-a9d8-005758522568.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"From Unexplained Fever to a Second Malignancy: Peripheral T-cell Lymphoma Following Long-term Olaparib Maintenance Therapy in Ovarian Cancer","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"fever of unknown origin, cytopenia, peripheral T-cell lymphoma, hemophagocytic lymphohistiocytosis, Olaparib, ovarian cancer","lastPublishedDoi":"10.21203/rs.3.rs-8684567/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8684567/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eFever of unknown origin (FUO) presents a common clinical challenge, with lymphoma being a significant neoplastic cause. Olaparib, a cornerstone in ovarian cancer maintenance therapy, has well-documented hematologic toxicities. However, its potential association with peripheral T-cell lymphoma (PTCL) remains unreported.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eWe report the case of a 77-year-old woman with advanced ovarian cancer on long-term maintenance therapy with olaparib and letrozole for over three years, who presented with fever and progressive cytopenia. Comprehensive infectious and rheumatologic workups were negative. Cell-free DNA sequencing revealed complex chromosomal abnormalities. \u003csup\u003e18\u003c/sup\u003eFDG PET/CT showed diffuse, intense skeletal hypermetabolism (SUVmax 16.0). Subsequently laboratory findings, including extreme hyperferritinemia (\u0026gt;\u0026thinsp;33511.2 ng/mL), elevated sIL-2R, hypertriglyceridemia, and hypofibrinogenemia, fulfilled the criteria for hemophagocytic lymphohistiocytosis (HLH). Bone marrow biopsy ultimately confirmed the diagnosis of peripheral T-cell lymphoma (PTCL) with marrow involvement. Despite discontinuing olaparib and initiating therapy for HLH and lymphoma, the patient's condition deteriorated rapidly, leading to death within one month of admission.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe case represents the first reported temporal association between long-term olaparib therapy and the development of PTCL in an ovarian cancer patient. It underscores the importance of considering secondary hematologic malignancies, including lymphoma, in patients on novel targeted therapies who present with unexplained FUO and cytopenias.\u003c/p\u003e","manuscriptTitle":"From Unexplained Fever to a Second Malignancy: Peripheral T-cell Lymphoma Following Long-term Olaparib Maintenance Therapy in Ovarian Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-16 20:09:39","doi":"10.21203/rs.3.rs-8684567/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"589d9ca3-984f-4650-9e0b-2e94847766ba","owner":[],"postedDate":"February 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-11T17:40:15+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-16 20:09:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8684567","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8684567","identity":"rs-8684567","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}