{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:21:14Z","timestamp":1778055674575,"version":"3.51.4"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Res."],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immune checkpoint inhibitors have transformed the treatment of hematolymphoid malignancies by enhancing antitumor immunity. These agents are associated with immune-related adverse events (irAEs), including hematologic toxicities such as autoimmune hemolytic anemia, immune-related thrombocytopenia (irTCP), and neutropenia. Although rare, hematologic irAEs (hem-irAEs) may reflect systemic immune activation and could serve as biomarkers of treatment response. Emerging evidence, particularly from observational studies and meta-analyses, suggests that patients who experience hem-irAEs may have lower rates of disease recurrence and improved survival outcomes. This manuscript reviews the mechanisms, incidence, and prognostic implications of hem-irAEs in patients with hematolymphoid malignancies, emphasizing their hypothesis-generating potential as predictive markers that warrant prospective validation.<\/jats:p>","DOI":"10.1007\/s44313-026-00135-4","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T01:26:20Z","timestamp":1778030780000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Checkpoint inhibitor\u2013induced hematologic immune-related adverse events and their association with disease recurrence in hematolymphoid malignancies: a clinical perspective"],"prefix":"10.1007","volume":"61","author":[{"given":"Chokri","family":"Ben Lamine","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amr","family":"Hanbali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghada","family":"ElGohary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanan","family":"Alkhaldi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riad","family":"El Fakih","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"Aljurf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"issue":"1","key":"135_CR1","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s40164-025-00684-x","volume":"14","author":"T Pan","year":"2025","unstructured":"Pan T, et al. Global burden and trends of hematologic malignancies based on Global Cancer Observatory 2022 and Global Burden of Disease 2021. Exp Hematol Oncol. 2025;14(1):98.","journal-title":"Exp Hematol Oncol"},{"key":"135_CR2","doi-asserted-by":"crossref","unstructured":"Sochacka-\u0106wik\u0142a A, M\u0105czy\u0144ski M, Regiec A. FDA-approved drugs for hematological malignancies-the last decade review. Cancers (Basel). 2021;14(1):87.\u00a0","DOI":"10.3390\/cancers14010087"},{"issue":"1","key":"135_CR3","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/s41392-023-01521-5","volume":"8","author":"L Tang","year":"2023","unstructured":"Tang L, et al. Immunotherapy in hematologic malignancies: achievements, challenges and future prospects. Signal Transduct Target Ther. 2023;8(1):306.","journal-title":"Signal Transduct Target Ther"},{"key":"135_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.oor.2024.100652","volume":"12","author":"I Desai","year":"2024","unstructured":"Desai I, Thakur S, Pagariya P. Current advances in immunotherapy for cancer. Oral Oncol Rep. 2024;12:100652.","journal-title":"Oral Oncol Rep"},{"key":"135_CR5","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1323914","volume":"14","author":"P Pophali","year":"2024","unstructured":"Pophali P, Varela JC, Rosenblatt J. Immune checkpoint blockade in hematological malignancies: current state and future potential. Front Oncol. 2024;14:1323914.","journal-title":"Front Oncol"},{"issue":"1","key":"135_CR6","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s13045-020-00947-6","volume":"13","author":"B Salik","year":"2020","unstructured":"Salik B, Smyth MJ, Nakamura K. Targeting immune checkpoints in hematological malignancies. J Hematol Oncol. 2020;13(1):111.","journal-title":"J Hematol Oncol"},{"issue":"2","key":"135_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.transci.2023.103685","volume":"62","author":"M Shouman","year":"2023","unstructured":"Shouman M, et al. Hematological toxicities of immune checkpoint inhibitors and the impact of blood transfusion and its microbiome on therapeutic efficacy and recipient\u2019s safety and survival outcome: a systematic narrative appraisal of where we are now! Transfus Apher Sci. 2023;62(2):103685.","journal-title":"Transfus Apher Sci"},{"key":"135_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2025.101321","volume":"74","author":"M Mohammed Saleh","year":"2025","unstructured":"Mohammed Saleh M, et al. Programmed death inhibitors in CNS B-cell lymphoma: a literature review. Blood Rev. 2025;74:101321.","journal-title":"Blood Rev"},{"issue":"10","key":"135_CR9","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1038\/s43018-023-00635-7","volume":"4","author":"T Wartewig","year":"2023","unstructured":"Wartewig T, et al. PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma. Nat Cancer. 2023;4(10):1508\u201325.","journal-title":"Nat Cancer"},{"issue":"5","key":"135_CR10","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70345","volume":"15","author":"S Xiang","year":"2025","unstructured":"Xiang S, Li S, Xu J. Unravelling T cell exhaustion through co-inhibitory receptors and its transformative role in cancer immunotherapy. Clin Transl Med. 2025;15(5):e70345.","journal-title":"Clin Transl Med"},{"key":"135_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112571","volume":"138","author":"Y Hu","year":"2024","unstructured":"Hu Y, et al. Reversal of T-cell exhaustion: mechanisms and synergistic approaches. Int Immunopharmacol. 2024;138:112571.","journal-title":"Int Immunopharmacol"},{"issue":"36","key":"135_CR12","doi-asserted-by":"publisher","first-page":"4073","DOI":"10.1200\/JCO.21.01440","volume":"39","author":"BJ Schneider","year":"2021","unstructured":"Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol. 2021;39(36):4073\u2013126.","journal-title":"J Clin Oncol"},{"issue":"1","key":"135_CR13","doi-asserted-by":"publisher","first-page":"e48","DOI":"10.1016\/S2352-3026(18)30175-3","volume":"6","author":"N Delanoy","year":"2019","unstructured":"Delanoy N, et al. Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study. Lancet Haematol. 2019;6(1):e48\u201357.","journal-title":"Lancet Haematol"},{"issue":"4","key":"135_CR14","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s11912-020-0897-9","volume":"22","author":"EP Darnell","year":"2020","unstructured":"Darnell EP, et al. Immune-related adverse events (irAEs): diagnosis, management, and clinical pearls. Curr Oncol Rep. 2020;22(4):39.","journal-title":"Curr Oncol Rep"},{"issue":"2","key":"135_CR15","doi-asserted-by":"publisher","first-page":"66","DOI":"10.14740\/jh1090","volume":"12","author":"T Ohashi","year":"2023","unstructured":"Ohashi T, et al. Incidence and risk of hematological adverse events associated with immune checkpoint inhibitors: a systematic literature review and meta-analysis. J Hematol. 2023;12(2):66\u201374.","journal-title":"J Hematol"},{"issue":"1","key":"135_CR16","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41419-023-06389-5","volume":"15","author":"L Meng","year":"2024","unstructured":"Meng L, et al. Mechanisms of immune checkpoint inhibitors: insights into the regulation of circular RNAS involved in cancer hallmarks. Cell Death Dis. 2024;15(1):3.","journal-title":"Cell Death Dis"},{"key":"135_CR17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01354","volume":"11","author":"NE Omar","year":"2020","unstructured":"Omar NE, et al. Diagnosis and management of hematological adverse events induced by immune checkpoint inhibitors: a systematic review. Front Immunol. 2020;11:1354.","journal-title":"Front Immunol"},{"key":"135_CR18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.991433","volume":"13","author":"J Taylor","year":"2023","unstructured":"Taylor J, et al. Checkpoint inhibitor immune-related adverse events: a focused review on autoantibodies and B cells as biomarkers, advancements and future possibilities. Front Immunol. 2023;13:991433.","journal-title":"Front Immunol"},{"issue":"25","key":"135_CR19","doi-asserted-by":"publisher","first-page":"3594","DOI":"10.1182\/blood.2020009016","volume":"139","author":"MH Kroll","year":"2022","unstructured":"Kroll MH, Rojas-Hernandez C, Yee C. Hematologic complications of immune checkpoint inhibitors. Blood. 2022;139(25):3594\u2013604.","journal-title":"Blood"},{"issue":"1","key":"135_CR20","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41392-025-02178-y","volume":"10","author":"J Nie","year":"2025","unstructured":"Nie J, et al. Deep insight into cytokine storm: from pathogenesis to treatment. Signal Transduct Target Ther. 2025;10(1):112.","journal-title":"Signal Transduct Target Ther"},{"key":"135_CR21","doi-asserted-by":"crossref","unstructured":"Cosenza M, Sacchi S, Pozzi S. Cytokine release syndrome associated with T-cell-based therapies for hematological malignancies: pathophysiology, clinical presentation, and treatment. Int J Mol Sci. 2021;22(14):7652.\u00a0","DOI":"10.3390\/ijms22147652"},{"issue":"1","key":"135_CR22","doi-asserted-by":"publisher","DOI":"10.1080\/20565623.2024.2422786","volume":"10","author":"X Zhang","year":"2024","unstructured":"Zhang X, et al. Cytokine release syndrome caused by immune checkpoint inhibitors: a case report and literature review. Future Sci OA. 2024;10(1):2422786.","journal-title":"Future Sci OA"},{"issue":"4","key":"135_CR23","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41571-021-00597-8","volume":"19","author":"Y Jing","year":"2022","unstructured":"Jing Y, et al. Harnessing big data to characterize immune-related adverse events. Nat Rev Clin Oncol. 2022;19(4):269\u201380.","journal-title":"Nat Rev Clin Oncol"},{"key":"135_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2025.102036","volume":"14","author":"MA Siddiqui","year":"2025","unstructured":"Siddiqui MA, et al. Immune-related adverse events in immunotherapy: challenges in diagnosis, monitoring, and management. Toxicol Rep. 2025;14:102036.","journal-title":"Toxicol Rep"},{"issue":"2","key":"135_CR25","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(2):158\u201368.","journal-title":"N Engl J Med"},{"issue":"2","key":"135_CR26","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/ejh.13187","volume":"102","author":"GE Tanios","year":"2019","unstructured":"Tanios GE, Doley PB, Munker R. Autoimmune hemolytic anemia associated with the use of immune checkpoint inhibitors for cancer: 68 cases from the Food and Drug Administration database and review. Eur J Haematol. 2019;102(2):157\u201362.","journal-title":"Eur J Haematol"},{"key":"135_CR27","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.ejca.2021.01.013","volume":"147","author":"R Kramer","year":"2021","unstructured":"Kramer R, et al. Hematological immune related adverse events after treatment with immune checkpoint inhibitors. Eur J Cancer. 2021;147:170\u201381.","journal-title":"Eur J Cancer"},{"key":"135_CR28","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.733890","volume":"12","author":"K Hradska","year":"2021","unstructured":"Hradska K, Hajek R, Jelinek T. Toxicity of immune-checkpoint inhibitors in hematological malignancies. Front Pharmacol. 2021;12:733890.","journal-title":"Front Pharmacol"},{"issue":"1","key":"135_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00277-021-04690-x","volume":"101","author":"P Ghanem","year":"2022","unstructured":"Ghanem P, et al. Current challenges of hematologic complications due to immune checkpoint blockade: a comprehensive review. Ann Hematol. 2022;101(1):1\u201310.","journal-title":"Ann Hematol"},{"issue":"5","key":"135_CR30","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1634\/theoncologist.2018-0574","volume":"24","author":"EJ Davis","year":"2019","unstructured":"Davis EJ, et al. Hematologic complications of immune checkpoint inhibitors. Oncologist. 2019;24(5):584\u20138.","journal-title":"Oncologist"},{"issue":"12","key":"135_CR31","doi-asserted-by":"publisher","first-page":"2584","DOI":"10.1038\/s41591-022-02094-6","volume":"28","author":"S Groha","year":"2022","unstructured":"Groha S, et al. Germline variants associated with toxicity to immune checkpoint blockade. Nat Med. 2022;28(12):2584\u201391.","journal-title":"Nat Med"},{"key":"135_CR32","doi-asserted-by":"publisher","first-page":"5378","DOI":"10.1182\/blood-2023-180648","volume":"142","author":"M Benkhadra","year":"2023","unstructured":"Benkhadra M, et al. Hematological toxicity of immune checkpoint inhibitors: real-world retrospective outcomes from a cohort study in Qatar. Blood. 2023;142:5378.","journal-title":"Blood"}],"container-title":["Blood Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s44313-026-00135-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s44313-026-00135-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s44313-026-00135-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:01:16Z","timestamp":1778054476000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s44313-026-00135-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["135"],"URL":"https:\/\/doi.org\/10.1007\/s44313-026-00135-4","relation":{},"ISSN":["2287-979X","2288-0011"],"issn-type":[{"value":"2287-979X","type":"print"},{"value":"2288-0011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]},"assertion":[{"value":"13 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19"}}