{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:01:23Z","timestamp":1787166083206,"version":"build-2736575974"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"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":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R\/R B-ALL). However, hepatic veno-occlusive disease\/sinusoidal obstruction syndrome (VOD\/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD\/SOS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reviewed seven cases of hepatic VOD\/SOS that developed either during INO salvage or after allogeneic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD\/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Four patients developed VOD\/SOS during INO salvage therapy (at 21 and 36\u00a0days post-INO1, 77\u00a0days post-INO3, and 21\u00a0days post-INO5), while three were diagnosed at 2, 5, and 10\u00a0days post-HSCT following INO-induced CR. Doppler ultrasonography revealed preserved portal vein flow (range 10.2\u201326.0\u00a0cm\/sec) and normal hepatic artery resistive index (RI, range 0.56\u20130.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD\/SOS progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Post-INO VOD\/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor. These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD\/SOS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s44313-025-00077-3","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T07:04:10Z","timestamp":1745305450000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Atypical features of hepatic veno-occlusive disease\/sinusoidal obstruction syndrome after inotuzumab ozogamicin in adult patients with acute lymphoblastic leukemia"],"prefix":"10.1007","volume":"60","author":[{"given":"Kyung-Hun","family":"Sung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daehun","family":"Kwag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gi June","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Soo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Eun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung-Sik","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki-Seong","family":"Eom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoo-Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Je","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Ki","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok-Goo","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2145-9131","authenticated-orcid":false,"given":"Jae-Ho","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"77_CR1","doi-asserted-by":"publisher","first-page":"489","DOI":"10.3389\/fimmu.2020.00489","volume":"11","author":"F Bonifazi","year":"2020","unstructured":"Bonifazi F, Barbato F, Ravaioli F, Sessa M, Defrancesco I, Arpinati M, et al. Diagnosis and treatment of VOD\/SOS after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2020;11:489. https:\/\/doi.org\/10.3389\/fimmu.2020.00489. (e-pub ahead of print 20200403).","journal-title":"Front Immunol"},{"issue":"14","key":"77_CR2","doi-asserted-by":"publisher","first-page":"2474","DOI":"10.1002\/cncr.32116","volume":"125","author":"HM Kantarjian","year":"2019","unstructured":"Kantarjian HM, DeAngelo DJ, Stelljes M, Liedtke M, Stock W, G\u00f6kbuget N, et al. Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer. 2019;125(14):2474\u201387. https:\/\/doi.org\/10.1002\/cncr.32116. e-pub ahead of print 20190328.","journal-title":"Cancer"},{"issue":"7","key":"77_CR3","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/s41409-023-01992-8","volume":"58","author":"M Mohty","year":"2023","unstructured":"Mohty M, Malard F, Alaskar AS, Aljurf M, Arat M, Bader P, et al. Diagnosis and severity criteria for sinusoidal obstruction syndrome\/veno-occlusive disease in adult patients: a refined classification from the European society for blood and marrow transplantation (EBMT). Bone Marrow Transplant. 2023;58(7):749\u201354. https:\/\/doi.org\/10.1038\/s41409-023-01992-8. e-pub ahead of print 2023\/04\/25.","journal-title":"Bone Marrow Transplant"},{"key":"77_CR4","doi-asserted-by":"publisher","first-page":"204062072110661","DOI":"10.1177\/20406207211066176","volume":"12","author":"J Lee","year":"2021","unstructured":"Lee J, Yoon JH, Kwag D, Lee JH, Kim TY, Min GJ, et al. Hepatic venoocclusive disease\/sinusoidal obstruction syndrome with normal portal vein flow mimicking aggravated chronic hepatic GVHD following inotuzumab ozogamicin salvage therapy: a case report of pathologic-radiologic discrepancy. Ther Adv Hematol. 2021;12:20406207211066176. https:\/\/doi.org\/10.1177\/20406207211066176. e-pub ahead of print 20211221.","journal-title":"Ther Adv Hematol"},{"issue":"3","key":"77_CR5","doi-asserted-by":"publisher","first-page":"623","DOI":"10.3390\/jcm11030623","volume":"11","author":"G Milone","year":"2022","unstructured":"Milone G, Bellofiore C, Leotta S, Milone GA, Cupri A, Duminuco A, et al. Endothelial dysfunction after hematopoietic stem cell transplantation: a review based on physiopathology. J Clin Med. 2022;11(3):623. https:\/\/doi.org\/10.3390\/jcm11030623. e-pub ahead of print 20220126.","journal-title":"J Clin Med"},{"issue":"1","key":"77_CR6","doi-asserted-by":"publisher","first-page":"e2018001","DOI":"10.4084\/mjhid.2018.001","volume":"10","author":"A Castellino","year":"2018","unstructured":"Castellino A, Guidi S, Dellacasa CM, Gozzini A, Donnini I, Nozzoli C, et al. Late-onset hepatic veno-occlusive disease after allografting: report of two cases with atypical clinical features successfully treated with defibrotide. Mediterr J Hematol Infect Dis. 2018;10(1):e2018001. https:\/\/doi.org\/10.4084\/mjhid.2018.001. e-pub ahead of print 20180101.","journal-title":"Mediterr J Hematol Infect Dis"},{"issue":"5","key":"77_CR7","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.2214\/ajr.158.5.1566656","volume":"158","author":"J Herbetko","year":"1992","unstructured":"Herbetko J, Grigg AP, Buckley AR, Phillips GL. Venoocclusive liver disease after bone marrow transplantation: findings at duplex sonography. AJR Am J Roentgenol. 1992;158(5):1001\u20135 e-pub ahead of print 1992\/05\/01.","journal-title":"AJR Am J Roentgenol"},{"issue":"7","key":"77_CR8","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1038\/s41409-021-01215-y","volume":"56","author":"JH Yoon","year":"2021","unstructured":"Yoon JH, Min GJ, Park SS, Park S, Lee SE, Cho BS, et al. Incidence and risk factors of hepatic veno-occlusive disease\/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation in adults with prophylactic ursodiol and intravenous heparin or prostaglandin E1. Bone Marrow Transplant. 2021;56(7):1603\u201313. https:\/\/doi.org\/10.1038\/s41409-021-01215-y. e-pub ahead of print 20210201.","journal-title":"Bone Marrow Transplant"},{"issue":"7","key":"77_CR9","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1158\/1078-0432.Ccr-16-0939","volume":"23","author":"M Guffroy","year":"2017","unstructured":"Guffroy M, Falahatpisheh H, Biddle K, Kreeger J, Obert L, Walters K, et al. Liver microvascular injury and thrombocytopenia of antibody-calicheamicin conjugates in cynomolgus monkeys-mechanism and monitoring. Clin Cancer Res. 2017;23(7):1760\u201370. https:\/\/doi.org\/10.1158\/1078-0432.Ccr-16-0939. e-pub ahead of print 20160928.","journal-title":"Clin Cancer Res"},{"issue":"2","key":"77_CR10","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1002\/hep.30222","volume":"69","author":"GB McDonald","year":"2019","unstructured":"McDonald GB, Freston JW, Boyer JL, DeLeve LD. Liver complications following treatment of hematologic malignancy with anti-CD22-calicheamicin (inotuzumab ozogamicin). Hepatology. 2019;69(2):831\u201344. https:\/\/doi.org\/10.1002\/hep.30222. e-pub ahead of print 20190118.","journal-title":"Hepatology"}],"container-title":["Blood Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s44313-025-00077-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s44313-025-00077-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s44313-025-00077-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T07:04:11Z","timestamp":1745305451000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s44313-025-00077-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,22]]},"references-count":10,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["77"],"URL":"https:\/\/doi.org\/10.1007\/s44313-025-00077-3","relation":{},"ISSN":["2287-979X","2288-0011"],"issn-type":[{"value":"2287-979X","type":"print"},{"value":"2288-0011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,22]]},"assertion":[{"value":"30 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in accordance with the Institutional Review Board guidelines of the Catholic Medical Center (KC23RISI0926).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28"}}