{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:17:58Z","timestamp":1789010278959,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T00:00:00Z","timestamp":1544054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012524","name":"American Lebanese Syrian Associated Charities","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100012524","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2019,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the presence of abnormal CD1a\u2010positive (CD1a\n                      <jats:sup>+<\/jats:sup>\n                      )\/CD207\n                      <jats:sup>+<\/jats:sup>\n                      histiocytes. Hemophagocytic lymphohistiocytosis (HLH) represents a spectrum of hyperinflammatory syndromes typified by the dysregulated activation of the innate and adaptive immune systems. Patients with LCH, particularly those with multisystem (MS) involvement, can develop severe hyperinflammation mimicking that observed in HLH. Nevertheless, to the authors\u2019 knowledge, little is known regarding the prevalence, timing, risk factors for development, and outcomes of children and young adults who develop HLH within the context of MS\u2010LCH (hereafter referred to LCH\u2010associated HLH).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To gain further insights, the authors conducted a retrospective, multicenter study and collected data regarding all patients diagnosed with MS\u2010LCH between 2000 and 2015.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 384 patients with MS\u2010LCH, 32 were reported by their primary providers to have met the diagnostic criteria for HLH, yielding an estimated 2\u2010year cumulative incidence of 9.3% \u00b1 1.6%. The majority of patients developed HLH at or after the diagnosis of MS\u2010LCH, and nearly one\u2010third (31%) had evidence of an intercurrent infection. Patient age &lt;2 years at the time of diagnosis of LCH; female sex; LCH involvement of the liver, spleen, and hematopoietic system; and a lack of bone involvement each were found to be independently associated with an increased risk of LCH\u2010associated HLH. Patients with MS\u2010LCH who met the criteria for HLH had significantly poorer 5\u2010year survival compared with patients with MS\u2010LCH who did not meet the criteria for HLH (69% vs 97%;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Given its inferior prognosis, further efforts are warranted to enhance the recognition and optimize the treatment of patients with LCH\u2010associated HLH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.31893","type":"journal-article","created":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T15:22:29Z","timestamp":1544109749000},"page":"963-971","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["A multicenter study of patients with multisystem Langerhans cell histiocytosis who develop secondary hemophagocytic lymphohistiocytosis"],"prefix":"10.1002","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3518-9790","authenticated-orcid":false,"given":"Deepak","family":"Chellapandian","sequence":"first","affiliation":[{"name":"Division of Haematology\/Oncology The Hospital for Sick Children Toronto Ontario Canada"},{"name":"Blood and Marrow Transplant Program, Cancer and Blood Disorders Institute Johns Hopkins All Children\u2019s Hospital St. Petersburg, Florida"},{"name":"Department of Oncology St. Jude Children\u2019s Research Hospital Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa R.","family":"Hines","sequence":"additional","affiliation":[{"name":"Division of Critical Care, Department of Pediatric Medicine St. Jude Children\u2019s Research Hospital Memphis 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