{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:11:20Z","timestamp":1792782680812,"version":"4.5.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":88,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e0 degli Studi di Genova","id":[{"id":"https:\/\/ror.org\/0107c5v14","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Secondary plasma cell leukemia (sPCL) represents one of the most aggressive forms of Multiple Myeloma (MM) progression and remains associated with poor outcomes despite the availability of novel immunotherapeutic approaches. Severe hypereosinophilia is exceptionally rare in plasma cell neoplasms and may occasionally occur as a paraneoplastic manifestation of aggressive disease biology. In selected cases, eosinophilic infiltration can result in life-threatening organ damage, particularly involving the cardiovascular system. We report the case of a 40-year-old woman with IgG lambda MM who achieved complete remission following daratumumab-based induction therapy, autologous stem cell transplantation, and lenalidomide maintenance. Approximately one year after transplantation, she developed rapidly progressive relapse characterized by constitutional symptoms, circulating clonal plasma cells, extensive bone marrow involvement, severe hypereosinophilia, and marked cardiac biomarker elevation. Comprehensive infectious, autoimmune, and molecular investigations excluded alternative causes of eosinophilia. Cardiac magnetic resonance imaging revealed diffuse myocardial edema, increased myocardial wall thickness, extensive subendocardial late gadolinium enhancement, regional wall motion abnormalities, and left ventricular mural thrombosis, findings highly suggestive of eosinophilic myocarditis with endomyocardial involvement consistent with Loeffler syndrome. Urgent cytoreductive therapy with cyclophosphamide and dexamethasone resulted in rapid normalization of eosinophil counts, substantial clinical improvement, and reduction of cardiac symptoms, strongly supporting a pathogenetic relationship between eosinophilia and plasma cell disease burden. Despite subsequent salvage therapies, including isatuximab-based treatment and the BCMA-directed bispecific antibody elranatamab, disease control remained transient and the patient ultimately died from refractory sPCL. This case highlights severe hypereosinophilia as a rare paraneoplastic manifestation of aggressive clonal evolution in MM and emphasizes the importance of prompt recognition of eosinophilic cardiac involvement. The close correlation between eosinophil kinetics and disease activity further suggests that hypereosinophilia may represent a potential clinical indicator of aggressive plasma cell disease evolution and warrants further investigation.<\/jats:p>","DOI":"10.1007\/s00277-026-07172-0","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T19:24:14Z","timestamp":1783625054000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Severe hypereosinophilia and eosinophilic myocarditis during secondary plasma cell leukemia: evidence of a paraneoplastic manifestation of aggressive myeloma evolution"],"prefix":"10.1007","volume":"105","author":[{"given":"Maria Elisabetta","family":"Catini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Garibotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita Castiglione","family":"Morelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Tagliafico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soncini","family":"Debora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Guolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto Massimo","family":"Lemoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Cagnetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"issue":"11","key":"7172_CR1","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1056\/NEJMra1011442","volume":"364","author":"A Palumbo","year":"2011","unstructured":"Palumbo A, Anderson KC (2011) Multiple myeloma. N Engl J Med 364(11):1046\u20131060. https:\/\/doi.org\/10.1056\/NEJMra1011442","journal-title":"N Engl J Med"},{"issue":"12","key":"7172_CR2","doi-asserted-by":"publisher","first-page":"e538","DOI":"10.1016\/S1470-2045(14)70442-5","volume":"15","author":"SV Rajkumar","year":"2014","unstructured":"Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, International Myeloma Working Group et al (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15(12):e538\u2013e548","journal-title":"Lancet Oncol"},{"issue":"1","key":"7172_CR3","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41572-024-00529-7","volume":"10","author":"F Malard","year":"2024","unstructured":"Malard F, Neri P, Bahlis NJ, Terpos E et al (2024) Multiple myeloma. Nat Rev Dis Primers 10(1):45","journal-title":"Nat Rev Dis Primers"},{"issue":"3","key":"7172_CR4","doi-asserted-by":"publisher","first-page":"e105","DOI":"10.1016\/S1470-2045(20)30756-7","volume":"22","author":"P Moreau","year":"2021","unstructured":"Moreau P, Kumar SK, San Miguel J, Davies F, International Myeloma Working Group et al (2021) Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group. Lancet Oncol 22(3):e105\u2013e118","journal-title":"Lancet Oncol"},{"issue":"12","key":"7172_CR5","doi-asserted-by":"publisher","first-page":"2376","DOI":"10.1182\/blood-2012-06-435139","volume":"120","author":"NWCJ van de Donk","year":"2012","unstructured":"van de Donk NWCJ, Lokhorst HM, Anderson KC, Richardson PG (2012) How I treat plasma cell leukemia. Blood 120(12):2376\u20132389. https:\/\/doi.org\/10.1182\/blood-2012-06-435139","journal-title":"Blood"},{"issue":"4","key":"7172_CR6","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.annonc.2025.01.022","volume":"36","author":"P Musto","year":"2025","unstructured":"Musto P, Engelhardt M, van de Donk NWCJ, Gay F et al (2025) European Myeloma Network. European Myeloma Network Group review and consensus statement on primary plasma cell leukemia. Ann Oncol 36(4):361\u2013374","journal-title":"Ann Oncol"},{"issue":"12","key":"7172_CR7","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/s41408-021-00587-0","volume":"11","author":"C Fern\u00e1ndez de Larrea","year":"2021","unstructured":"Fern\u00e1ndez de Larrea C, Kyle R, Rosi\u00f1ol L, Paiva B, International Myeloma Working Group et al (2021) Primary plasma cell leukemia: consensus definition by the International Myeloma Working Group according to peripheral blood plasma cell percentage. Blood Cancer J 11(12):192","journal-title":"Blood Cancer J"},{"key":"7172_CR8","doi-asserted-by":"publisher","unstructured":"Al-Hadidi S, van Rhee F, Anderson LD Jr (2026) How I treat plasma cell leukemia. Blood 1. https:\/\/doi.org\/10.1182\/blood.2025032145","DOI":"10.1182\/blood.2025032145"},{"issue":"9","key":"7172_CR9","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1586\/erc.11.118","volume":"9","author":"R Wassmuth","year":"2011","unstructured":"Wassmuth R, Schulz-Menger J (2011) Cardiovascular magnetic resonance imaging of myocardial inflammation. Expert Rev Cardiovasc Ther 9(9):1193\u20131201","journal-title":"Expert Rev Cardiovasc Ther"},{"issue":"16","key":"7172_CR10","doi-asserted-by":"publisher","first-page":"4733","DOI":"10.3390\/jcm13164733","volume":"13","author":"D Marchetti","year":"2024","unstructured":"Marchetti D, Buzzi F, Di Febo R, Modugno S et al (2024) Role of cardiac magnetic resonance in inflammatory and infiltrative cardiomyopathies: a narrative review. J Clin Med 13(16):4733","journal-title":"J Clin Med"},{"issue":"1","key":"7172_CR11","first-page":"14","volume":"72","author":"F Franchi","year":"1984","unstructured":"Franchi F, De Rosa F, Seminara P, Calvieri S et al (1984) Hypereosinophilic syndrome and plasmocytoma. Report of a case and review of the literature. Acta Haematol 72(1):14\u201320","journal-title":"Acta Haematol"},{"issue":"5","key":"7172_CR12","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1093\/ajcp\/103.5.583","volume":"103","author":"L Glantz","year":"1995","unstructured":"Glantz L, Rintels P, Samoszuk M, Medeiros LJ (1995) Plasma cell myeloma associated with eosinophilia. Am J Clin Pathol 103(5):583\u2013587","journal-title":"Am J Clin Pathol"},{"issue":"11","key":"7172_CR13","doi-asserted-by":"publisher","first-page":"e305","DOI":"10.1515\/cclm-2015-0232","volume":"53","author":"C Robier","year":"2015","unstructured":"Robier C, Egger M, Wiesinger K, Aigner R, Neubauer M (2015) Progression from light chain myeloma to secondary plasma cell leukemia accompanied by peripheral blood eosinophilia. Clin Chem Lab Med 53(11):e305\u2013e307","journal-title":"Clin Chem Lab Med"},{"key":"7172_CR14","doi-asserted-by":"crossref","unstructured":"Zhong J, Liu X, Liu J, Xiao S, Gu X, Liu Z (2026) Case report: a case of non-secretory multiple myeloma presenting with eosinophilia: diagnostic challenges and a focused literature review. Front Oncol 16:1833556","DOI":"10.3389\/fonc.2026.1833556"},{"issue":"3","key":"7172_CR15","first-page":"565","volume":"51","author":"Y Sonoda","year":"1993","unstructured":"Sonoda Y (1993) Humoral regulation of eosinophilopoiesis by interleukin-3, granulocyte\/macrophage colony-stimulating factor (GM\u2013CSF) and interleukin-5. Nihon Rinsho 51(3):565\u2013570","journal-title":"Nihon Rinsho"},{"issue":"1","key":"7172_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1158\/2326-6066.CIR-13-0196","volume":"2","author":"BP Davis","year":"2014","unstructured":"Davis BP, Rothenberg ME (2014) Eosinophils and cancer. Cancer Immunol Res 2(1):1\u20138","journal-title":"Cancer Immunol Res"},{"issue":"7","key":"7172_CR17","doi-asserted-by":"publisher","first-page":"e69191","DOI":"10.1371\/journal.pone.0070554","volume":"8","author":"TW Wong","year":"2013","unstructured":"Wong TW, Kita H, Hanson CA, Walters DK, Arendt BK, Jelinek DF (2013) Induction of malignant plasma cell proliferation by eosinophils. PLoS ONE 8(7):e69191","journal-title":"PLoS ONE"},{"issue":"5","key":"7172_CR18","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1111\/j.1365-2141.2006.06038.x","volume":"132","author":"A Tefferi","year":"2006","unstructured":"Tefferi A, Patnaik MM, Pardanani A (2006) Eosinophilia: secondary, clonal and idiopathic. Br J Haematol 132(5):468\u2013492","journal-title":"Br J Haematol"},{"issue":"1","key":"7172_CR19","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/all.15544","volume":"78","author":"P Valent","year":"2023","unstructured":"Valent P, Klion AD, Roufosse F et al (2023) Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes. Allergy 78(1):47\u201359","journal-title":"Allergy"},{"issue":"2","key":"7172_CR20","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1081\/IPH-120003748","volume":"24","author":"CK Wong","year":"2002","unstructured":"Wong CK, Zhang J, Ip WK, Lam CW (2002) Intracellular signal transduction in eosinophils and its clinical significance. Immunopharmacol Immunotoxicol 24(2):165\u2013186","journal-title":"Immunopharmacol Immunotoxicol"},{"issue":"14","key":"7172_CR21","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.3390\/cells13141180","volume":"13","author":"M Caminati","year":"2024","unstructured":"Caminati M, Brussino L, Carlucci M, Carlucci P, Carpagnano LF, Caruso C, Cosmi L, D\u2019Amore S, Del Giacco S, Detoraki A et al (2024) Managing patients with hypereosinophilic syndrome: a statement from the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC). Rev Cells 13(14):1180","journal-title":"Rev Cells"},{"issue":"1","key":"7172_CR22","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.jaci.2009.07.025","volume":"125","author":"DG Powe","year":"2010","unstructured":"Powe DG, Groot Kormelink T, Sisson M, Blokhuis BJ, Kramer MF, Jones NS, Redegeld FA (2010) Evidence for the involvement of free light chain immunoglobulins in allergic and nonallergic rhinitis. J Allergy Clin Immunol 125(1):139\u201345.e1-3","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"7172_CR23","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1111\/bjh.14488","volume":"176","author":"NM Butt","year":"2017","unstructured":"Butt NM, Lambert J, Ali S, Beer PA, Cross NC, Duncombe A, Ewing J, Harrison CN, Knapper S, McLornan D, Mead AJ, Radia D, Bain BJ (2017) British Committee for Standards in Haematology. Guideline for the investigation and management of eosinophilia. Br J Haematol 176(4):553\u2013572","journal-title":"Br J Haematol"},{"issue":"5","key":"7172_CR24","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1002\/ajh.27287","volume":"99","author":"W Shomali","year":"2024","unstructured":"Shomali W, Gotlib J (2024) World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management. Am J Hematol 99(5):946\u2013968","journal-title":"Am J Hematol"},{"issue":"9","key":"7172_CR25","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.clml.2024.04.007","volume":"24","author":"K Sasaki","year":"2024","unstructured":"Sasaki K, Kantarjian H, Montalban\u2013Bravo G, Hammond D et al (2024) Eosinophilia During Lenalidomide Therapy in Myelodysplastic Syndrome. Clin Lymphoma Myeloma Leuk 24(9):629\u2013633","journal-title":"Clin Lymphoma Myeloma Leuk"},{"issue":"6","key":"7172_CR26","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1177\/0018578717717394","volume":"52","author":"A Shanbhag","year":"2017","unstructured":"Shanbhag A, Pritchard ER, Chatterjee K, Hammond DA (2017) Highly probable drug reaction with eosinophilia and systemic symptoms syndrome associated with lenalidomide. Hosp Pharm 52(6):408\u2013411","journal-title":"Hosp Pharm"},{"issue":"6","key":"7172_CR27","first-page":"e00260","volume":"5","author":"A Toma","year":"2017","unstructured":"Toma A, Rapoport AP, Burke A, Sachdeva A (2017) Lenalidomide-induced eosinophilic pneumonia. Respirol Case Rep 5(6):e00260","journal-title":"Respirol Case Rep"},{"issue":"2","key":"7172_CR28","first-page":"136","volume":"43","author":"HS Lee","year":"2011","unstructured":"Lee HS, Park LC, Shin SH, Lee SU, Chang HK, Huh B, Jung GS, Kim MH, Kim YS (2011) Successful chemotherapy following autologous stem cell transplantation in multiple myeloma and multi-organ dysfunction with infiltration of eosinophils: a case report. Cancer Res Treat 43(2):136\u2013140","journal-title":"Cancer Res Treat"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-026-07172-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-07172-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-07172-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:02:47Z","timestamp":1791212567000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-026-07172-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":28,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,11]]}},"alternative-id":["7172"],"URL":"https:\/\/doi.org\/10.1007\/s00277-026-07172-0","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-9966075\/v1","asserted-by":"object"}]},"ISSN":["1432-0584"],"issn-type":[{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]},"assertion":[{"value":"8 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethics approval was not required.","order":1,"name":"Ethics","label":"Ethics declaration","group":{"name":"EthicsHeading","label":"Declaration"}},{"value":"Written informed consent was obtained for publication of the case report and any accompanying images from the patient or the legal representative.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declaration"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declaration"}}],"article-number":"442"}}