{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:40:57Z","timestamp":1760139657343,"version":"build-2065373602"},"reference-count":76,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T00:00:00Z","timestamp":1650672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Hemophagocytic lymphohistiocytosis (HLH) is a rare, elusive, and life-threatening condition that is characterized by the pathologic and uncontrolled secondary activation of the cytotoxic T-cells, natural killer cells (NK-cells), and macrophages of the innate immune system. This condition can develop in sporadic or familial contexts associated with hematological malignancies, as a paraneoplastic syndrome, or linked to an infection related to immune system deficiency. This leads to the systemic inflammation responsible for the overall clinical manifestations. Diagnosis should be thorough, and treatment should be initiated as soon as possible. In the current manuscript, we focus on classifying the HLH spectrum, describing the pathophysiology and the tools needed to search for and correctly identify HLH, and the current therapeutic opportunities. We also present the first case of a multiple myeloma patient that developed HLH following therapy with the ixazomib-lenalidomide-dexamethasone protocol.<\/jats:p>","DOI":"10.3390\/jpm12050678","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T21:39:45Z","timestamp":1650749985000},"page":"678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mechanistic Insights in Hemophagocytic Lymphohistiocytosis: Subsequent Acute Hepatic Failure in a Multiple Myeloma Patient Following Therapy with Ixazomib-Lenalidomide-Dexamethasone"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8292-911X","authenticated-orcid":false,"given":"Catalin","family":"Constantinescu","sequence":"first","affiliation":[{"name":"Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"},{"name":"Department of Anesthesia and Intensive Care, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"},{"name":"Intensive Care Unit, Emergency Hospital, 400006 Cluj-Napoca, Romania"},{"name":"Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bobe","family":"Petrushev","sequence":"additional","affiliation":[{"name":"Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"},{"name":"Department of Pathology, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioana","family":"Rus","sequence":"additional","affiliation":[{"name":"Department of Pathology, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania"},{"name":"Department of Hematology, Ion Chiricuta Clinical Cancer Center, 400015 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4034-5471","authenticated-orcid":false,"given":"Horia","family":"Stefanescu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania"},{"name":"Department of Gastroenterology, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Otilia","family":"Frasinariu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Margarit","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"},{"name":"Intensive Care Unit, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delia","family":"Dima","sequence":"additional","affiliation":[{"name":"Department of Hematology, Ion Chiricuta Clinical Cancer Center, 400015 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5500-1519","authenticated-orcid":false,"given":"Ciprian","family":"Tomuleasa","sequence":"additional","affiliation":[{"name":"Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"},{"name":"Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"},{"name":"Department of Hematology, Ion Chiricuta Clinical Cancer Center, 400015 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1146\/annurev-pathol-020117-043625","article-title":"Hemophagocytic Lymphohistiocytosis","volume":"13","author":"Berliner","year":"2018","journal-title":"Annu. 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