{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:57:21Z","timestamp":1789178241719,"version":"build-2803163510"},"reference-count":20,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T00:00:00Z","timestamp":1554249600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["j. immunotherapy cancer"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s40425-019-0582-4","type":"journal-article","created":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T12:03:11Z","timestamp":1554292991000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Severe cytokine release syndrome resulting in purpura fulminans despite successful response to nivolumab therapy in a patient with pleomorphic carcinoma of the lung: a case report"],"prefix":"10.1136","volume":"7","author":[{"given":"Osamu","family":"Honjo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terufumi","family":"Kubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiko","family":"Sugaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Nishizaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Hirohashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Torigoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,4,3]]},"reference":[{"key":"582_CR1","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1002\/art.40043","volume":"69","author":"ME Suarez-Almazor","year":"2017","unstructured":"Suarez-Almazor ME, Kim ST, Abdel-Wahab N, Diab A. Review: immune-related adverse events with use of checkpoint inhibitors for immunotherapy of Cancer. Arthritis Rheumatol. 2017;69:687\u201399.","journal-title":"Arthritis Rheumatol"},{"key":"582_CR2","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.ejca.2017.02.016","volume":"77","author":"N Malissen","year":"2017","unstructured":"Malissen N, Lacotte J, Du-Thanh A, Gaudy-Marqueste C, Guillot B, Grob JJ. Macrophage activation syndrome: a new complication of checkpoint inhibitors. Eur J Cancer. 2017;77:88\u20139.","journal-title":"Eur J Cancer"},{"key":"582_CR3","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s40425-018-0384-0","volume":"6","author":"A Hantel","year":"2018","unstructured":"Hantel A, Gabster B, Cheng JX, Golomb H, Gajewski TF. Severe hemophagocytic lymphohistiocytosis in a melanoma patient treated with ipilimumab + nivolumab. J Immunother Cancer. 2018;6:73.","journal-title":"J Immunother Cancer"},{"key":"582_CR4","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s40425-018-0365-3","volume":"6","author":"M Sadaat","year":"2018","unstructured":"Sadaat M, Jang S. Hemophagocytic lymphohistiocytosis with immunotherapy: brief review and case report. J Immunother Cancer. 2018;6:49.","journal-title":"J Immunother Cancer"},{"key":"582_CR5","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1093\/annonc\/mdx113","volume":"28","author":"D Shah","year":"2017","unstructured":"Shah D, Shrestha R, Ramlal R, Hatton J, Saeed H. Pembrolizumab associated hemophagocytic lymphohistiocytosis. Ann Oncol. 2017;28:1403.","journal-title":"Ann Oncol"},{"key":"582_CR6","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1093\/annonc\/mdx602.001","volume":"28","author":"M Takeshita","year":"2017","unstructured":"Takeshita M, Anai S, Mishima S, Inoue K. Coincidence of immunotherapy-associated hemophagocytic syndrome and rapid tumor regression. Ann Oncol. 2017;28:186\u20139.","journal-title":"Ann Oncol"},{"key":"582_CR7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s40425-017-0224-7","volume":"5","author":"J King","year":"2017","unstructured":"King J, de la Cruz J, Lutzky J. Ipilimumab-induced thrombotic thrombocytopenic purpura (TTP). J Immunother Cancer. 2017;5:19.","journal-title":"J Immunother Cancer"},{"key":"582_CR8","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.1016\/j.jtho.2017.08.022","volume":"12","author":"S Teraoka","year":"2017","unstructured":"Teraoka S, Fujimoto D, Morimoto T, Kawachi H, Ito M, Sato Y, et al. Early immune-related adverse events and association with outcome in advanced non-small cell lung cancer patients treated with Nivolumab: a prospective cohort study. J Thorac Oncol. 2017;12:1798\u2013805.","journal-title":"J Thorac Oncol"},{"key":"582_CR9","doi-asserted-by":"crossref","unstructured":"Owen DH, Wei L, Bertino EM, Edd T, Villalona-Calero MA, He K, et al. Incidence, risk factors, and effect on survival of immune-related adverse events in patients with non-small-cell lung cancer. Clin Lung Cancer. 2018;19:e893\u2013900.","DOI":"10.1016\/j.cllc.2018.08.008"},{"key":"582_CR10","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.lungcan.2017.11.019","volume":"115","author":"K Sato","year":"2018","unstructured":"Sato K, Akamatsu H, Murakami E, Sasaki S, Kanai K, Hayata A, et al. Correlation between immune-related adverse events and efficacy in non-small cell lung cancer treated with nivolumab. Lung Cancer. 2018;115:71\u20134.","journal-title":"Lung Cancer"},{"key":"582_CR11","doi-asserted-by":"publisher","first-page":"838","DOI":"10.4065\/mcp.2010.0099","volume":"85","author":"LC Pelosof","year":"2010","unstructured":"Pelosof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clin Proc. 2010;85:838\u201354.","journal-title":"Mayo Clin Proc"},{"key":"582_CR12","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s40425-018-0343-9","volume":"6","author":"A Shimabukuro-Vornhagen","year":"2018","unstructured":"Shimabukuro-Vornhagen A, Godel P, Subklewe M, Stemmler HJ, Schlosser HA, Schlaak M, et al. Cytokine release syndrome. J Immunother Cancer. 2018;6:56.","journal-title":"J Immunother Cancer"},{"key":"582_CR13","doi-asserted-by":"publisher","first-page":"2613","DOI":"10.1002\/art.38690","volume":"66","author":"L Fardet","year":"2014","unstructured":"Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 2014;66:2613\u201320.","journal-title":"Arthritis Rheumatol"},{"key":"582_CR14","doi-asserted-by":"publisher","first-page":"3037","DOI":"10.1002\/art.39295","volume":"67","author":"L Cifaldi","year":"2015","unstructured":"Cifaldi L, Prencipe G, Caiello I, Bracaglia C, Locatelli F, De Benedetti F, et al. Inhibition of natural killer cell cytotoxicity by interleukin-6: implications for the pathogenesis of macrophage activation syndrome. Arthritis Rheumatol. 2015;67:3037\u201346.","journal-title":"Arthritis Rheumatol"},{"key":"582_CR15","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.jaci.2015.12.1314","volume":"138","author":"S Humblet-Baron","year":"2016","unstructured":"Humblet-Baron S, Franckaert D, Dooley J, Bornschein S, Cauwe B, Schonefeldt S, et al. IL-2 consumption by highly activated CD8 T cells induces regulatory T-cell dysfunction in patients with hemophagocytic lymphohistiocytosis. J Allergy Clin Immunol. 2016;138:200\u201309 e8.","journal-title":"J Allergy Clin Immunol"},{"key":"582_CR16","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1111\/j.1538-7836.2008.02989.x","volume":"6","author":"WJ Cao","year":"2008","unstructured":"Cao WJ, Niiya M, Zheng XW, Shang DZ, Zheng XL. Inflammatory cytokines inhibit ADAMTS13 synthesis in hepatic stellate cells and endothelial cells. J Thromb Haemost. 2008;6:1233\u20135.","journal-title":"J Thromb Haemost"},{"key":"582_CR17","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1056\/NEJMra1703481","volume":"378","author":"MA Postow","year":"2018","unstructured":"Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158\u201368.","journal-title":"N Engl J Med"},{"key":"582_CR18","doi-asserted-by":"publisher","first-page":"e26642","DOI":"10.1002\/pbc.26642","volume":"64","author":"SJ Rotz","year":"2017","unstructured":"Rotz SJ, Leino D, Szabo S, Mangino JL, Turpin BK, Pressey JG. Severe cytokine release syndrome in a patient receiving PD-1-directed therapy. Pediatr Blood Cancer. 2017;64:e26642.","journal-title":"Pediatr Blood Cancer"},{"key":"582_CR19","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1159\/000496933","volume":"12","author":"H Oda","year":"2019","unstructured":"Oda H, Ishihara M, Miyahara Y, Nakamura J, Kozuka Y, Iwasa M, et al. First case of cytokine release syndrome after nivolumab for gastric cancer. Case Rep Oncol. 2019;12:147\u201356.","journal-title":"Case Rep Oncol"},{"key":"582_CR20","doi-asserted-by":"publisher","first-page":"913","DOI":"10.2217\/imt-2018-0025","volume":"10","author":"L Zhao","year":"2018","unstructured":"Zhao L, Yang Y, Li W, Li T, Gao Q. Nivolumab-induced cytokine-release syndrome in relapsed\/refractory Hodgkin\u2019s lymphoma: a case report and literature review. Immunotherapy. 2018;10:913\u20137.","journal-title":"Immunotherapy."}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40425-019-0582-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s40425-019-0582-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40425-019-0582-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T17:47:26Z","timestamp":1601056046000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1186\/s40425-019-0582-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,3]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["582"],"URL":"https:\/\/doi.org\/10.1186\/s40425-019-0582-4","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,3]]},"assertion":[{"value":"18 October 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable, not a trial.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Appropriate consent was obtained from the patient.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"97"}}