{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T01:36:19Z","timestamp":1775871379675,"version":"3.50.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Johann Wolfgang Goethe-Universit\u00e4t, Frankfurt am Main"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We present the case of a 58-year-old female patient who presented with an extramedullary B-ALL relapse after prior allogenic HSCT and blinatumomab therapy. The patient died from complications of a drug-induced acute liver failure after a salvage therapy combining inotuzumab ozogamicin (InO)-based induction followed by consolidation with high dose MTX and pegaspargase based on the GMALL protocol for older ALL patients. After a diagnosis of the extramedullary relapse in the form of a retro vesical chloroma, the patient received an individualized multi-agent chemotherapy based on induction chemotherapy for older patients in combination with InO. After four administrations of InO, in combination with vincristine, dexamethasone, cytarabine, and cyclophosphamide, CT-imaging showed a reduction in volume of the chloroma and response to therapy. Consolidation with high-dose methotrexate and pegaspargase was administered. The patient developed toxic liver damage manifested by hyperbilirubinemia and progressive hepatic encephalopathy. The diagnostic criteria for VOD were met, and therapy with defibrotide was initiated. Liver biopsy revealed no histological signs of VOD but instead steatohepatitis indicative of drug-induced toxicity. The patient ultimately died of hemorrhagic shock through postinterventional hemorrhage after liver biopsy. In conclusion, although InO shows promising results in the therapy of r\/r ALL with and without additional chemotherapy, the combination with MTX and pegaspargase in an intensively pretreated patient with relapse after HCST may impart an increased risk for liver-related toxicity. Special caution is required when assessing fitness for further liver toxic regimens. A key takeaway is also the reminder that InO can cause liver damage not only in the form of VOD but also through direct hepatocellular toxicity.<\/jats:p>","DOI":"10.1007\/s00277-023-05495-w","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T09:02:21Z","timestamp":1700816541000},"page":"489-498","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Liver failure after treatment with inotuzumab and polychemotherapy including PEG-asparaginase in a patient with relapsed Philadelphia chromosome\u2013negative acute lymphoblastic leukemia"],"prefix":"10.1007","volume":"103","author":[{"given":"Daniel","family":"Fischer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Toenges","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kati","family":"Kiil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Michalik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Thalhammer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gesine","family":"Bug","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"G\u00f6kbuget","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-029X","authenticated-orcid":false,"given":"Fabian","family":"Lang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,11,24]]},"reference":[{"key":"5495_CR1","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1034\/j.1600-0609.2000.9r200.x","volume":"64","author":"E Carreras","year":"2000","unstructured":"Carreras E (2000) Veno-occlusive disease of the liver after hemopoietic cell transplantation. 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RT declares that no conflicts of interest exist. KK declares that no conflicts of interest exist. SM declares that no conflicts of interest exist. AT declares that no conflicts of interest exist. GB reports honoraria from Novartis, Gilead, BMS, Pfizer, and Jazz, travel grants from Neovii, Gilead, and Jazz, and consultancy for Affimed. NG has received honoraria from (advisory boards, invited talks) Incyte, Amgen, Novartis, and Pfizer and has received institutional funding from Incyte, Amgen, and Pfizer. FL has received honoraria from Bristol Myers Squibb, Incyte, and Celgene, and has received institutional funding and honoraria from Novartis.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}