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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

Year: 2026

Type: article

Abstract: Background: 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.

Source: Journal of Hepatocellular Carcinoma

DOI: 10.2147/jhc.s656165