Chronic portal hypertension following inotuzumab ozogamicin in a low-risk patient: a case of overriding baseline risk and long-term management

Inotuzumab ozogamicin (InO) is effective for relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) but is associated with hepatotoxicity, particularly sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), which leads to portal hypertension (PH). We report a case of a 50-year-old woman who, after receiving InO, developed SOS/VOD and subsequent chronic PH, manifesting as recurrent variceal bleeding approximately 18 months post-treatment. A literature review highlights diagnostic advances using non-invasive tools like transient elastography, the central role of calicheamicin-induced endothelial injury and complement activation in pathogenesis, and risk mitigation through ursodiol prophylaxis and avoidance of dual-alkylator conditioning regimens. The case further illustrates that PH can present with atypical hemodynamics, such as preserved portal flow and absence of cirrhosis, and may emerge as a chronic sequela long after acute SOS/VOD resolution. Quantitative risk assessment using a validated model (CIBMTR) revealed a very low pre-treatment SOS/VOD risk (2.64%), highlighting that InO-induced injury can override a favorable baseline risk profile. This underscores the importance of long-term monitoring for PH, even after resolution of acute SOS/VOD and achievement of leukemia remission, to optimize outcomes in InO-treated patients.