Rare Case Report: Therapy-Related Acute Promyelocytic Leukemia (t-APL) in a Young Non-HBV Female After TACE Plus Sintilimab-Lenvatinib for HCC — A Clinical Alert and Literature Review

Rong Yu,1,* Xulin Shi,1,* Huaxi Fan,1,* Guishu Wu,2,* Jing Zhang,1,* Xiangyu Deng,1 Xiaolong Liu,1 Mingyue Rao,1 Jianwen Zhang1,3,41Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Oncology, The First People’s Hospital of Liangshan Yi Autonomous Prefecture, Liangshan, Sichuan, 615000, People’s Republic of China; 3Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, 646000, People’s Republic of China; 4Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianwen Zhang, Email [email protected]: Transarterial chemoembolization (TACE) combined with PD-1 immune checkpoint inhibitor plus lenvatinib is a standard first-line therapy for unresectable hepatocellular carcinoma (HCC). Therapy-related acute promyelocytic leukemia (t-APL) is a rare but life-threatening secondary hematologic malignancy. Reports of t-APL following this triple regimen in non-HBV young female HCC patients remain extremely limited.Methods: We report a 30-year-old non-HBV female patient with moderately-differentiated HCC diagnosed incidentally in early pregnancy, who received pregnancy termination followed by oxaliplatin-fluorouracil-based TACE, then sintilimab plus lenvatinib maintenance. Clinical, laboratory, bone marrow, imaging and histopathological data were collected. We further performed a systematic review of published t-APL cases in HCC patients treated with targeted-immune therapy up to May 2026.Results: Approximately 12 months after treatment initiation, the patient developed oral mucosal ecchymosis, fatigue and anorexia. Serial blood tests demonstrated progressive thrombocytopenia and increasing circulating promyelocytes. Bone-marrow examination and FISH confirmed PML/RARA-positive t-APL. Due to economic burden, the patient refused standard all-trans retinoic acid (ATRA) plus arsenic trioxide and died 3 months after t-APL diagnosis. Combined with 11 previously reported cases (total n=12 globally), the median latency from targeted-immunotherapy commencement to t-APL onset was 11 months (range 6– 18 months). Pathogenesis may involve synergistic genotoxic injury from TACE chemotherapy, PD-1-mediated immune dysregulation, lenvatinib-associated myelotoxicity and host individual susceptibility.Conclusion: t-APL is a rare fatal complication of TACE plus sintilimab-lenvatinib for HCC, mostly occurring within 1 year of therapy initiation. Mandatory monthly hematologic monitoring is required during this high-risk window. Prompt bone-marrow evaluation and PML/RARA fusion testing should be performed for unexplained cytopenia or circulating immature myeloid cells to enable timely ATRA-arsenic-based intervention.Keywords: hepatocellular carcinoma, lenvatinib, sintilimab, therapy-related acute promyelocytic leukemia, PML/RARA fusion gene, immune checkpoint inhibitor, TACE