{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:39:20Z","timestamp":1787020760075,"version":"build-2736575974"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,5]],"date-time":"2025-01-05T00:00:00Z","timestamp":1736035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,5]],"date-time":"2025-01-05T00:00:00Z","timestamp":1736035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hematol Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma rarely presents with circulating lymphoma cells (CL) at diagnosis. Previous studies were limited by small sample size precluding robust analysis. Hence, we evaluated the prognostic relevance of CL cells in newly diagnosed DLBCL patients. Based on peripheral blood (PB) immunophenotyping, patients were grouped into CL\u2009+\u2009and CL\u2212. CL was defined as detectable clonally restricted B-cells that matched the actual or expected B-cell immunophenotype of DLBCL. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS) and diagnosis-to-treatment interval (DTI). Among the 1266 patients with DLBCL, 621 had PB flow at diagnosis, and after excluding patients not meeting eligibility criteria, 588 cases remained. Among these, 85 (15%) were CL\u2009+\u2009and 503 were CL- (85%). Patients in CL\u2009+\u2009group were younger (67 vs. 70 years,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03) with a higher proportion of non-bulky disease (85% vs. 56%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), normal albumin (79% vs. 54%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), and\n                    <jats:italic>MYC\/BCL2<\/jats:italic>\n                    and\/or\n                    <jats:italic>BCL6<\/jats:italic>\n                    rearrangements (18% vs. 7%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.003) compared to the CL\u2009\u2212\u2009group. Patients with CL at diagnosis had significantly inferior PFS and OS compared with those without CL. After adjusting for factors associated with inferior PFS and OS in univariable analysis, presence of CL remained significantly associated with inferior PFS (HR\u2009=\u20092.04, 95%CI\u2009=\u20091.47\u20132.84,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and OS (HR\u2009=\u20091.61, 95%CI\u2009=\u20091.1\u20132.36,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01), respectively. There was no significant difference in DTI between the two groups. Given the prognostic relevance associated with presence of CL, clinicians should consider checking PB flow at diagnosis in all newly diagnosed DLBCL patients.\n                  <\/jats:p>","DOI":"10.1186\/s13045-024-01658-y","type":"journal-article","created":{"date-parts":[[2025,1,5]],"date-time":"2025-01-05T12:16:08Z","timestamp":1736079368000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of circulating lymphoma cells at diagnosis on outcomes in patients with newly diagnosed de novo diffuse large B-cell lymphoma"],"prefix":"10.1186","volume":"18","author":[{"given":"Sayan Mullick","family":"Chowdhury","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subodh","family":"Bhatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Voorhees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin","family":"Annunzio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazeed","family":"Sawalha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Sigmund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Hanel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalit","family":"Sehgal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lapo","family":"Alinari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Baiocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kami","family":"Maddocks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Christian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narendranath","family":"Epperla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,5]]},"reference":[{"issue":"1","key":"1658_CR1","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.pathol.2017.09.006","volume":"50","author":"S Li","year":"2018","unstructured":"Li S, Young KH, Medeiros LJ. Diffuse large B-cell lymphoma. Pathology. 2018;50(1):74\u201387.","journal-title":"Pathology"},{"issue":"6","key":"1658_CR2","doi-asserted-by":"publisher","first-page":"443","DOI":"10.3322\/caac.21357","volume":"66","author":"LR Teras","year":"2016","unstructured":"Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. Cancer J Clin. 2016;66(6):443\u201359.","journal-title":"Cancer J Clin"},{"issue":"12","key":"1658_CR3","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1097\/01.pas.0000182405.65041.8b","volume":"29","author":"DA Arber","year":"2005","unstructured":"Arber DA, George TI. Bone marrow biopsy involvement by Non-hodgkin\u2019s lymphoma: frequency of lymphoma types, patterns, blood involvement, and discordance with other sites in 450 specimens. Am J Surg Pathol. 2005;29(12):1549\u201357.","journal-title":"Am J Surg Pathol"},{"issue":"17","key":"1658_CR4","doi-asserted-by":"publisher","first-page":"4166","DOI":"10.1002\/cncr.27381","volume":"118","author":"H Takahashi","year":"2012","unstructured":"Takahashi H, Tomita N, Yokoyama M, et al. Prognostic impact of extranodal involvement in diffuse large B-cell lymphoma in the Rituximab era. Cancer. 2012;118(17):4166\u201372.","journal-title":"Cancer"},{"issue":"5","key":"1658_CR5","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1136\/jclinpath-2013-201520","volume":"67","author":"V Sovani","year":"2014","unstructured":"Sovani V, Harvey C, Haynes AP, McMillan AK, Clark DM, O\u2019Connor SR. Bone marrow trephine biopsy involvement by lymphoma: review of histopathological features in 511 specimens and correlation with diagnostic biopsy, aspirate and peripheral blood findings. J Clin Pathol. 2014;67(5):389\u201395.","journal-title":"J Clin Pathol"},{"issue":"5","key":"1658_CR6","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1111\/j.1365-2141.2012.09209.x","volume":"158","author":"D Muringampurath-John","year":"2012","unstructured":"Muringampurath-John D, Jaye DL, Flowers CR, et al. Characteristics and outcomes of diffuse large B\u2010cell lymphoma presenting in leukaemic phase. Br J Haematol. 2012;158(5):608\u201314.","journal-title":"Br J Haematol"},{"key":"1658_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12881-017-0381-z","volume":"18","author":"D Zou","year":"2017","unstructured":"Zou D, Yi S, Cui R, et al. BCL-2 and MYC gain\/amplification is correlated with central nervous system involvement in diffuse large B cell lymphoma at leukemic phase. BMC Med Genet. 2017;18:1\u20136.","journal-title":"BMC Med Genet"},{"issue":"8","key":"1658_CR8","doi-asserted-by":"publisher","first-page":"e815","DOI":"10.1016\/j.clml.2022.04.009","volume":"22","author":"JJ Kuhlman","year":"2022","unstructured":"Kuhlman JJ, Moustafa MA, Jiang L, et al. Leukemic high grade B cell lymphoma is associated with MYC translocation, double hit\/triple hit status, transformation, and CNS disease risk: the Mayo Clinic experience. Clin Lymphoma Myeloma Leuk. 2022;22(8):e815\u201325.","journal-title":"Clin Lymphoma Myeloma Leuk"}],"container-title":["Journal of Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-024-01658-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13045-024-01658-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-024-01658-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,5]],"date-time":"2025-01-05T13:02:26Z","timestamp":1736082146000},"score":1,"resource":{"primary":{"URL":"https:\/\/jhoonline.biomedcentral.com\/articles\/10.1186\/s13045-024-01658-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,5]]},"references-count":8,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1658"],"URL":"https:\/\/doi.org\/10.1186\/s13045-024-01658-y","relation":{},"ISSN":["1756-8722"],"issn-type":[{"value":"1756-8722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,5]]},"assertion":[{"value":"14 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the institutional review board and was conducted in compliance with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"NE: Research funding: Beigene, Lilly, and Incyte; Speakers Bureau for Beigene and Genentech; Ad boards for ADC Therapeutics, Lilly, and Ipsen; Honorarium from Novartis. TJV: Advisory Board: Genmab\/AbbVie, ADC Therapeutics. Consultancy: Novartis, Recordati, Genmab. Research Funding: Kite, Viracta, Incyte\/Morphosys, Genmab\/AbbVie, Recordati. DAB: Advisory Board: Novartis, Nurix Therapeutics, ADC Therapeutics. Research Funding: Novartis, Kite\/Gilead, Accutar, Nurix Therapeutics, Incyte, GenMab, BeiGene. Astra Zeneca.BC Advisory Board: Ipsen, AstraZeneca; Research Support: Genentech, Acerta, Millenium, Kite, Bristol Myers Squibb KM: Consulting: AbbVie, ADC Therapeutics, AstraZeneca\/Acerta, Beigene, BMS, Caribou, Genentech, Genmab, Gilead\/KITE, Incyte, Janssen, Lilly, Morphosys, Pharmacyclics.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4"}}