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.

我们介绍了一名 58 岁女性患者的病例，她在先前的同种异体 HSCT 和博纳吐单抗治疗后出现髓外 B-ALL 复发。该患者在接受基于伊珠单抗奥佐米星 (InO) 诱导的挽救治疗后，根据针对老年 ALL 患者的 GMALL 方案，采用高剂量 MTX 和培门冬酶进行巩固治疗，最终死于药物引起的急性肝衰竭并发症。在诊断为膀胱后绿瘤形式的髓外复发后，该患者接受了基于老年患者诱导化疗并联合 InO 的个体化多药化疗。InO 与长春新碱、地塞米松、阿糖胞苷和环磷酰胺联合给药四次后，CT 成像显示绿色瘤体积减少，对治疗的反应也有所减少。使用大剂量甲氨蝶呤和培门冬酶进行巩固治疗。患者出现中毒性肝损伤，表现为高胆红素血症和进行性肝性脑病。满足 VOD 的诊断标准，并开始去纤苷治疗。肝活检未发现 VOD 的组织学迹象，而是显示脂肪性肝炎，表明药物引起的毒性。患者最终因肝活检后介入后出血而死于失血性休克。总之，尽管 InO 在有或没有额外化疗的 r/r ALL 治疗中显示出有希望的结果，但在 HCST 后复发的强化预处理患者中与 MTX 和培门冬酶联合使用可能会增加肝脏相关毒性的风险。在评估是否适合进一步的肝毒性治疗方案时需要特别小心。一个重要的要点还提醒人们，In2O不仅可以通过视频点播的形式造成肝损伤，还可以通过直接的肝细胞毒性造成肝损伤。