{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:44:57Z","timestamp":1793277897272,"version":"4.5.0"},"reference-count":61,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To provide an overview of clinical sequelae and emerging treatment options for hemophagocytic lymphohistiocytosis (HLH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Sources:<\/jats:title>\n                    <jats:p>A literature search was conducted using the search terms \u201chemophagocytic lymphohistiocytosis,\u201d \u201chemophagocytic syndrome,\u201d \u201cmacrophage activation syndrome,\u201d and \u201ctreatment\u201d on Ovid and PubMed from January 1, 2017, through September 28, 2022.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Selection and Data Extraction:<\/jats:title>\n                    <jats:p>Relevant clinical trials, meta-analyses, case reports, review articles, package inserts, and guidelines to identify current and emerging therapeutic options for the management of HLH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Synthesis:<\/jats:title>\n                    <jats:p>Genetic disorders and secondary causes may trigger HLH in both children and adults. Notable improvements in the diagnosis of HLH were seen with implementation of the HLH-2004 standard diagnostic criteria; however, timely and accurate identification of HLH remain significant barriers to optimal management. Multiagent immunochemotherapy are the backbone of aggressive therapy for acutely ill patients with HLH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Relevance to Patient Care and Clinical Practice:<\/jats:title>\n                    <jats:p>The global coronavirus 2019 (COVID-19) pandemic and emerging immune effector cell therapies have served to highlight the concerns with immune dysregulation and subsequent HLH precipitation. Without prompt identification and treatment, HLH can be fatal. Historically, the clinician\u2019s armamentarium for managing HLH was sparse, with etoposide-based protocols serving as the standard of care. Relapsed or refractory disease portends a poor prognosis and requires additional treatment options. Second- or subsequent-line options now include hematopoietic stem cell transplantation, emapalumab, alemtuzumab, anakinra, ruxolitinib, and tocilizumab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Improvements in diagnostic methods and novel immunosuppressive treatment strategies, including noncytotoxic immunochemotherapy, have transformed the therapeutic landscape. Unfortunately, many unanswered questions remain. Additional studies are required to optimize dosing, schedules, treatment sequences, and indications for novel treatment options.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10600280221134719","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T05:59:23Z","timestamp":1667973563000},"page":"867-879","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":34,"title":["A Review of Current and Emerging Therapeutic Options for Hemophagocytic Lymphohistiocytosis"],"prefix":"10.1177","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6494-675X","authenticated-orcid":false,"given":"Jenna","family":"Summerlin","sequence":"first","affiliation":[{"name":"Division of Pharmacy Practice, The University of Texas at Austin College of Pharmacy, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7466-7516","authenticated-orcid":false,"given":"Drew A.","family":"Wells","sequence":"additional","affiliation":[{"name":"Internal Medicine, Department of Pharmacy, Methodist University Hospital, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0987-3356","authenticated-orcid":false,"given":"Mary Kate","family":"Anderson","sequence":"additional","affiliation":[{"name":"The University of Texas Medical Branch, Galveston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7032-0398","authenticated-orcid":false,"given":"Zachery","family":"Halford","sequence":"additional","affiliation":[{"name":"Union University College of Pharmacy, Jackson, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)61951-7."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27929."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-356261."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00443367."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.5045\/br.2021.2020323."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.06.053."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-324533."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1482543."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.614704."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61048-X."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.608492."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25308."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2010.551153."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2015.1.177."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0606.000608."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428190701713630."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1532\/IJH97.07012."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2016.05.001."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000005361."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2018894618."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-020-02941-3."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.38690."},{"issue":"2","key":"e_1_3_2_26_2","first-page":"197","article-title":"Hemophagocytic lymphohistiocytosis. 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