{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:43:34Z","timestamp":1790772214096,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2019,1,18]],"date-time":"2019-01-18T00:00:00Z","timestamp":1547769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,1,18]],"date-time":"2019-01-18T00:00:00Z","timestamp":1547769600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>\n                    Treatment of hematological malignancy with antibody\u2010drug conjugates (ADCs) may cause liver injury. ADCs deliver a toxic moiety into antigen\u2010expressing tumor cells, but may also injure hepatic sinusoids (sinusoidal obstruction syndrome; SOS). We studied patients who received an anti\u2010CD22\/calicheamicin conjugate (inotuzumab ozogamicin; InO) to gain insight into mechanisms of sinusoidal injury, given that there are no CD22\n                    <jats:sup>+<\/jats:sup>\n                    cells in the normal liver, but nonspecific uptake of ADCs by liver sinusoidal endothelial cells (LSECs). Six hundred thirty\u2010eight patients (307 with acute lymphocytic leukemia [ALL], 311 with non\u2010Hodgkin\u2019s lymphoma [NHL]) were randomized to either InO or standard chemotherapy (controls). While blinded to treatment assignment, we reviewed all cases with hepatobiliary complications to adjudicate the causes. Frequency of SOS among patients who received InO was 5 of 328 (1.5%), compared to no cases among 310 control patients. Drug\u2010induced liver injury (DILI) developed in 26 (7.9%) InO recipients and 3 (1%) controls. Intrahepatic cholestasis (IHC) was observed in 4.9% of InO recipients and in 5.5% of controls. Subsequent to the randomization study, 113 patients with ALL underwent allogeneic hematopoietic cell transplantation (HCT); frequency of SOS in those previously exposed to InO was 21 of 79 (27%) versus 3 of 34 (9%) in controls. An exploratory multivariate model identified a past history of liver disease and thrombocytopenia before conditioning therapy as dominant risk factors for SOS after transplant.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Frequencies of SOS and DILI after inotuzumab ozogamicin treatment were 1.5% and 7.9%, respectively, compared to none and 1% among controls who received standard chemotherapy. These data suggest that ADCs that do not target antigens present in the normal liver have a relatively low frequency of SOS, but a relatively high frequency of DILI.\n                  <\/jats:p>","DOI":"10.1002\/hep.30222","type":"journal-article","created":{"date-parts":[[2018,8,18]],"date-time":"2018-08-18T08:39:31Z","timestamp":1534581571000},"page":"831-844","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":52,"title":["Liver Complications Following Treatment of Hematologic Malignancy With Anti\u2010CD22\u2010Calicheamicin (Inotuzumab Ozogamicin)"],"prefix":"10.1097","volume":"69","author":[{"given":"George B.","family":"McDonald","sequence":"first","affiliation":[{"name":"University of Washington,Seattle,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Freston","sequence":"additional","affiliation":[{"name":"University of Connecticut Health 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