{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:57:43Z","timestamp":1789178263710,"version":"build-2803163510"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICPis) are widely used clinically to improve the prognosis of various cancers. However, little is known about their hematologic immune-related adverse events (irAEs). This study aimed to comprehensively investigate the incidence and clinical characteristics of irAEs induced by ICPis through a cross-organ research approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients who received at least one ICPi dose at the Osaka International Cancer Institute between January 2014 and September 2021 were reviewed, irrespective of their tumor type. We analyzed the cumulative incidence of hematological irAEs and investigated the clinical course of patients who underwent bone marrow examination owing to suspected hematological irAEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During the study period, 1500 patients in total received ICPis. Based on clinical data and the histopathological evaluation of bone marrow samples, we identified seven cases of hematologic irAEs (four of immune thrombocytopenia, two of hemophagocytic lymphohistiocytosis, and one of agranulocytosis). Additionally, we observed six cases of primary hematologic disease, four of bone marrow findings consistent with cytopenia and subsequent recovery secondary to infections or cytotoxic agents, two of bone marrow involvement by primary cancer, and one of an unknown cause. With the median follow-up of 297\u00a0days (0\u20132087\u00a0days), the cumulative incidence rates of hematologic irAEs at 90\u00a0days and 1\u00a0year were 0.1% (95% CI, 0.0\u20130.4) and 0.4% (95% CI, 0.2\u20131.0), respectively. None of the patients with hematological irAEs died.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Severe hematological irAEs are rare but can be life-threatening. When hematological abnormalities are detected during ICPi therapy, it is important to explore the possibility of irAEs, including bone marrow abnormalities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jjco\/hyaf118","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T07:20:22Z","timestamp":1751872822000},"page":"1247-1252","source":"Crossref","is-referenced-by-count":1,"title":["Cross-organ examination of hematologic toxicities from immune checkpoint inhibitors: insights from real-world data"],"prefix":"10.1093","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7580-6445","authenticated-orcid":false,"given":"Sayako","family":"Yuda","sequence":"first","affiliation":[{"name":"Department of Hematology, Osaka International Cancer Institute , 3-1-69, Otemae, Chuo-ku, Osaka-shi, Osaka, 541-8567 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuma","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Hematology, Osaka International Cancer Institute , 3-1-69, Otemae, Chuo-ku, Osaka-shi, Osaka, 541-8567 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Shingai","sequence":"additional","affiliation":[{"name":"Department of Hematology, Osaka International Cancer Institute , 3-1-69, Otemae, Chuo-ku, Osaka-shi, Osaka, 541-8567 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Department of Hematology, Osaka International Cancer Institute , 3-1-69, Otemae, Chuo-ku, Osaka-shi, Osaka, 541-8567 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Fuji","sequence":"additional","affiliation":[{"name":"Department of Hematology, Osaka International Cancer Institute , 3-1-69, Otemae, Chuo-ku, Osaka-shi, Osaka, 541-8567 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Masaie","sequence":"additional","affiliation":[{"name":"Department of Hematology, Osaka International Cancer Institute , 3-1-69, Otemae, Chuo-ku, Osaka-shi, Osaka, 541-8567 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Hematology, Osaka International Cancer Institute , 3-1-69, Otemae, Chuo-ku, Osaka-shi, Osaka, 541-8567 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Hematology, Osaka International Cancer Institute , 3-1-69, Otemae, Chuo-ku, Osaka-shi, Osaka, 541-8567 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"2025110905433078100_ref1","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1056\/NEJMoa1412082","article-title":"Nivolumab in previously untreated melanoma without BRAF mutation","volume":"372","author":"Robert","year":"2015","journal-title":"N Engl J Med"},{"key":"2025110905433078100_ref2","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1\u2013positive non\u2013small-cell lung cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N Engl J Med"},{"key":"2025110905433078100_ref3","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1016\/j.annonc.2022.10.001","article-title":"Management of toxicities from immunotherapy: ESMO clinical practice guideline for diagnosis, treatment and follow-up","volume":"33","author":"Haanen","year":"2022","journal-title":"Ann Oncol"},{"key":"2025110905433078100_ref4","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1200\/JCO.2017.77.6385","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline","volume":"36","author":"Brahmer","year":"2018","journal-title":"J Clin Oncol"},{"key":"2025110905433078100_ref5","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ejca.2018.07.129","article-title":"Haematological toxicities with immunotherapy in patients with cancer: a systematic review and meta-analysis","volume":"103","author":"Petrelli","year":"2018","journal-title":"Eur J Cancer"},{"key":"2025110905433078100_ref6","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1634\/theoncologist.2018-0574","article-title":"Hematologic complications of immune checkpoint inhibitors","volume":"24","author":"Davis","year":"2019","journal-title":"Oncologist"},{"key":"2025110905433078100_ref7","doi-asserted-by":"publisher","first-page":"e48","DOI":"10.1016\/S2352-3026(18)30175-3","article-title":"Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study","volume":"6","author":"Delanoy","year":"2019","journal-title":"Lancet Haematol"},{"key":"2025110905433078100_ref8","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/hon.2743","article-title":"Hematological toxicities in immune checkpoint inhibitors: a pharmacovigilance study from 2014 to 2019","volume":"38","author":"Ye","year":"2020","journal-title":"Hematol Oncol"},{"key":"2025110905433078100_ref9","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.ejca.2021.01.013","article-title":"Hematological immune related adverse events after treatment with immune checkpoint inhibitors","volume":"147","author":"Kramer","year":"2021","journal-title":"Eur J Cancer"},{"key":"2025110905433078100_ref10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00277-021-04690-x","article-title":"Current challenges of hematologic complications due to immune checkpoint blockade: a comprehensive review","volume":"101","author":"Ghanem","year":"2022","journal-title":"Ann Hematol"},{"key":"2025110905433078100_ref11","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1016\/S1470-2045(21)00333-8","article-title":"Treatment-related adverse events of PD-1 and PD-L1 inhibitor-based combination therapies in clinical trials: a systematic review and meta-analysis","volume":"22","author":"Zhou","year":"2021","journal-title":"Lancet Oncol"},{"key":"2025110905433078100_ref12","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.ejca.2019.07.014","article-title":"Haematological immune-related adverse events with immune checkpoint inhibitors, how to manage?","volume":"122","author":"Michot","year":"2019","journal-title":"Eur J Cancer"},{"key":"2025110905433078100_ref13","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1080\/01621459.1999.10474144","article-title":"A proportional hazards model for the subdistribution of a competing risk","volume":"94","author":"Fine","year":"1999","journal-title":"J Am Stat Assoc"},{"key":"2025110905433078100_ref14","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software \u201cEZR\u201d for medical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant"},{"key":"2025110905433078100_ref15","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.blre.2016.05.001","article-title":"Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: a systematic scoping review","volume":"30","author":"Hayden","year":"2016","journal-title":"Blood Rev"},{"key":"2025110905433078100_ref16","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1056\/NEJMcp1810479","article-title":"Immune thrombocytopenia","volume":"381","author":"Cooper","year":"2019","journal-title":"N Engl J Med"},{"key":"2025110905433078100_ref17","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.hoc.2021.12.001","article-title":"Autoimmune hemolytic anemia: diagnosis and differential diagnosis","volume":"36","author":"Scheckel","year":"2022","journal-title":"Hematol Oncol Clin North Am"},{"key":"2025110905433078100_ref18","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1056\/NEJMra2033982","article-title":"Autoimmune hemolytic anemias","volume":"385","author":"Berentsen","year":"2021","journal-title":"N Engl J Med"},{"key":"2025110905433078100_ref19","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1111\/1759-7714.13281","article-title":"Clinical diagnosis and treatment recommendations for immune checkpoint inhibitor-related hematological adverse events","volume":"11","author":"Zhuang","year":"2020","journal-title":"Thorac Cancer"},{"key":"2025110905433078100_ref20","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/ejh.13187","article-title":"Autoimmune hemolytic anemia associated with the use of immune checkpoint inhibitors for cancer: 68 cases from the Food and Drug Administration database and review","volume":"102","author":"Tanios","year":"2019","journal-title":"Eur J Haematol"},{"key":"2025110905433078100_ref21","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1002\/ajh.25448","article-title":"Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors","volume":"94","author":"Leaf","year":"2019","journal-title":"Am J Hematol"},{"key":"2025110905433078100_ref22","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1016\/j.autrev.2017.04.012","article-title":"Pathogenesis of immune thrombocytopenia","volume":"16","author":"Audia","year":"2017","journal-title":"Autoimmun Rev"},{"key":"2025110905433078100_ref23","doi-asserted-by":"publisher","first-page":"4639","DOI":"10.1182\/blood-2010-04-281717","article-title":"Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents","volume":"116","author":"Bao","year":"2010","journal-title":"Blood"},{"key":"2025110905433078100_ref24","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1182\/blood-2007-12-129262","article-title":"Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell\u2013depleting therapy with rituximab","volume":"112","author":"Stasi","year":"2008","journal-title":"Blood"}],"container-title":["Japanese Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jjco\/article-pdf\/55\/11\/1247\/63851461\/hyaf118.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jjco\/article-pdf\/55\/11\/1247\/63851461\/hyaf118.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T10:43:36Z","timestamp":1762685016000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jjco\/article\/55\/11\/1247\/8213508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,25]]},"references-count":24,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,7,25]]},"published-print":{"date-parts":[[2025,11,8]]}},"URL":"https:\/\/doi.org\/10.1093\/jjco\/hyaf118","relation":{},"ISSN":["1465-3621"],"issn-type":[{"value":"1465-3621","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11]]},"published":{"date-parts":[[2025,7,25]]}}}