{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:11:55Z","timestamp":1778217115554,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytometry Part B Clinical"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Central nervous system involvement in multiple myeloma (CNS\u2010MM) is a rare complication usually observed in advanced relapse or refractory settings. The detection of malignant plasma cells in the cerebrospinal fluid (CSF) on the basis of morphology and flow cytometry (FCM) confirms this extra\u2010medullary lesion. The records of 459\u2009MM patients treated between 2016 and 2025 were reviewed, identifying four cases with CSF involvement. CSF and bone marrow samples were processed and analyzed on the basis of morphology and FCM using a dedicated 9\u2010color panel to detect malignant plasma cells. Interleukin\u20106 (IL\u20106) and interleukin\u201010 (IL\u201010) concentrations were also measured in the CSF using Cytometric Bead Assay. Three patients were in complete remission when CSF analysis revealed CNS\u2010MM. Two patients presented no cerebral lesions, although spinal cord compression was observed for one of them. Two patients presented interference in FCM analysis, supporting the penetration of daratumumab into the CSF. Interleukin measures in the CSF showed low or undetectable IL\u201010 levels but elevated IL\u20106 concentrations in some cases. Overall prognosis was poor, with the death of three patients and only one remaining alive at 2\u2009years. CNS\u2010MM could be the first sign of relapse among patients previously in complete remission. It should be envisaged in the case of any myeloma patient with unexplained neurological symptoms, even when imaging is negative. Flow\u2010cytometry panels need to be optimized for plasma\u2010cell detection, especially among patients treated with anti\u2010CD38 antibodies. Identifying patients at risk remains crucial, but prognostic biomarkers such as IL\u20106 still require validation.<\/jats:p>","DOI":"10.1002\/cyto.b.70035","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:01:28Z","timestamp":1778216488000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Central nervous system involvement in multiple myeloma as a first manifestation of relapse and potential diagnostic pitfall"],"prefix":"10.1002","author":[{"given":"Jessy","family":"Ranaivomanana","sequence":"first","affiliation":[{"name":"Laboratoire d'H\u00e9matologie Groupe Hospitalier de la R\u00e9gion Mulhouse Sud Alsace  Mulhouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e9a","family":"Ryffel","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie Groupe Hospitalier de la R\u00e9gion Mulhouse Sud Alsace  Mulhouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muriel","family":"Newinger","sequence":"additional","affiliation":[{"name":"Service Clinique d'H\u00e9matologie Groupe Hospitalier de la R\u00e9gion Mulhouse Sud Alsace  Mulhouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amira","family":"Mejri","sequence":"additional","affiliation":[{"name":"Service Clinique d'H\u00e9matologie Groupe Hospitalier de la R\u00e9gion Mulhouse Sud Alsace  Mulhouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Ojeda\u2010Uribe","sequence":"additional","affiliation":[{"name":"Service Clinique d'H\u00e9matologie Groupe Hospitalier de la R\u00e9gion Mulhouse Sud Alsace  Mulhouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"De Marini","sequence":"additional","affiliation":[{"name":"Service de Radiologie Groupe Hospitalier de la R\u00e9gion Mulhouse Sud Alsace  Mulhouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Dr\u00e9nou","sequence":"additional","affiliation":[{"name":"Service Clinique d'H\u00e9matologie Groupe Hospitalier de la R\u00e9gion Mulhouse Sud Alsace  Mulhouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magali","family":"Le Garff\u2010Tavernier","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie Biologique H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re, APHP, Sorbonne Universit\u00e9, Inserm UMR S 1138  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Lefebvre","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie Groupe Hospitalier de la R\u00e9gion Mulhouse Sud Alsace  Mulhouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8124-3925","authenticated-orcid":false,"given":"Agathe","family":"Debliquis","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie Groupe Hospitalier de la R\u00e9gion Mulhouse Sud Alsace  Mulhouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.clml.2013.11.004","article-title":"Patterns of central nervous system involvement in relapsed and refractory multiple myeloma","volume":"14","author":"Abdallah A.","year":"2014","journal-title":"Clinical Lymphoma, Myeloma & Leukemia"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/8563098","article-title":"Aggressive central nervous system relapse after autologous stem cell transplant in multiple myeloma: Case reports and literature review","volume":"2020","author":"Bergantim R.","year":"2020","journal-title":"Case Reports in Hematology"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/j.1365-2141.2004.05199.x","article-title":"Multiple myeloma involving the central nervous system: High frequency of chromosome 17p13.1 (p53) deletions","volume":"127","author":"Chang H.","year":"2004","journal-title":"British Journal of Haematology"},{"key":"e_1_2_8_5_1","first-page":"684","article-title":"VS38 identifies myeloma cells with dim CD38 expression and plasma cells following daratumumab therapy","volume":"152","author":"Courville E. L.","year":"2019","journal-title":"American Journal of Clinical Pathology"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.22169"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.22226"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/cyto.b.21981","article-title":"ESCCA\/ISCCA protocol for analysis of cerebrospinal fluid by multiparametric flow cytometry in hematological malignancies","volume":"100","author":"Del Principe M. I.","year":"2021","journal-title":"Cytometry. Part B, Clinical Cytometry"},{"issue":"7","key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.3324\/haematol.2020.248518","article-title":"Multiple myeloma with central nervous system relapse","volume":"105","author":"Egan P. A.","year":"2020","journal-title":"Haematologica"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0052385","article-title":"Cytokine profile in human eyes: Contribution of a new cytokine combination for differential diagnosis between intraocular lymphoma and uveitis","volume":"8","author":"Fisson S.","year":"2013","journal-title":"PLoS One"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/cyto.b.21265","article-title":"Immunophenotype of normal vs. myeloma plasma cells: Toward antibody panel standardization in MRD","volume":"90","author":"Flores\u2010Montero J.","year":"2016","journal-title":"Cytometry. Part B, Clinical Cytometry"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.thromres.2015.03.019","article-title":"Thalidomide and multiple myeloma serum synergistically induce a hemostatic imbalance in endothelial cells in vitro","volume":"135","author":"Gao Y.","year":"2015","journal-title":"Thrombosis Research"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/cyto.b.21837","article-title":"Artifactual kappa light chain restriction of marrow hematogones: A potential diagnostic pitfall in minimal residual disease assessment of plasma cell myeloma patients on daratumumab","volume":"98","author":"Jiang X. Y.","year":"2020","journal-title":"Cytometry. Part B, Clinical Cytometry"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/ajh.24351","article-title":"Central nervous system involvement by multiple myeloma: A multi\u2010institutional retrospective study of 172 patients","volume":"91","author":"Jurczyszyn A.","year":"2016","journal-title":"American Journal of Hematology"},{"key":"e_1_2_8_15_1","first-page":"403","article-title":"Daratumumab interference in flow cytometry producing false kappa light\u2010chain restriction in plasma cells","volume":"52","author":"Kleinot W.","year":"2021","journal-title":"Laboratoriums Medizin"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2017.46","article-title":"Multiple myeloma","volume":"3","author":"Kumar S. K.","year":"2017","journal-title":"Nature Reviews. Disease Primers"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"11553","DOI":"10.1007\/s13277-016-5098-7","article-title":"Role of interleukin\u20106 in cancer progression and therapeutic resistance","volume":"37","author":"Kumari N.","year":"2016","journal-title":"Tumour Biology"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1097\/01.HS9.0000850904.60513.b3","article-title":"Multiple myeloma with central nervous system relapse in the era of novel drugs: A multicenter retrospective study from the Croatian cooperative Group for Hematological Malignancies (KROHEM)","volume":"6","author":"Mitrovic Z.","year":"2022","journal-title":"HemaSphere"},{"key":"e_1_2_8_19_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neurol.2022.06.014","article-title":"CSF biomarkers in primary CNS lymphoma","volume":"179","author":"Nguyen\u2010Them L.","year":"2023","journal-title":"Revue Neurologique (Paris)"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1365-2257.2006.00741.x","article-title":"Detection of malignant haematopoietic cells in the cerebrospinal fluid by conventional cytology and flow cytometry","volume":"28","author":"N\u00fcckel H.","year":"2006","journal-title":"Clinical and Laboratory Haematology"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","first-page":"e368","DOI":"10.3324\/haematol.2017.169235","article-title":"Long\u2010term CD38 saturation by daratumumab interferes with diagnostic myeloma cell detection","volume":"102","author":"Oberle A.","year":"2017","journal-title":"Haematologica"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0044-1787535"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.clml.2016.08.010","article-title":"Myelomatous involvement of the central nervous system","volume":"16","author":"Paludo J.","year":"2016","journal-title":"Clinical Lymphoma, Myeloma & Leukemia"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2022.934240","article-title":"Central nervous system myeloma and unusual extramedullary localizations: Real\u2010life practical guidance","volume":"12","author":"Sammartano V.","year":"2022","journal-title":"Frontiers in Oncology"},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.7150\/thno.38533","article-title":"Nanobody\u2010based CD38\u2010specific heavy chain antibodies induce killing of multiple myeloma and other hematological malignancies","volume":"10","author":"Schriewer L.","year":"2020","journal-title":"Theranostics"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1111\/j.1365-2141.2004.04853.x","article-title":"Clinical follow\u2010up indicates differential accuracy of MRI and immunocytology of CSF for diagnosing neoplastic meningitis","volume":"124","author":"Zeiser R.","year":"2004","journal-title":"British Journal of Haematology"}],"container-title":["Cytometry Part B: Clinical Cytometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cyto.b.70035","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cyto.b.70035","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cyto.b.70035","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:01:31Z","timestamp":1778216491000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cyto.b.70035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":25,"alternative-id":["10.1002\/cyto.b.70035"],"URL":"https:\/\/doi.org\/10.1002\/cyto.b.70035","archive":["Portico"],"relation":{},"ISSN":["1552-4949","1552-4957"],"issn-type":[{"value":"1552-4949","type":"print"},{"value":"1552-4957","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,7]]},"assertion":[{"value":"2025-12-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cyto.b.70035"}}