Therapy-related acute promyelocytic leukemia (t-APL) is rare and often linked to previous treatment with alkylating agents or topoisomerase II inhibitors. This report describes three cases of t-APL treated at the Haematology Department of Cosenza Hospital between 2022 and 2024, which occurred after alkylating agents and exemestane, alkylating agents and radiation therapy, alkylating agents, taxane, and checkpoint inhibitor, respectively. Each case was managed with a different therapeutic approach. The first case involved a 71-year-old man with colorectal and breast cancer, who developed low-risk t-APL and achieved complete remission (CR) with ATRA alone. A second 71-year-old man case with colorectal cancer developed high-risk t-APL with PML/RARA and FLT3-ITD fusion transcripts; he achieved CR with idarubicin and ATRA despite severe sepsis and acute heart failure. The third case involved a 74-year-old man with lung squamous cell carcinoma who developed intermediate-risk t-APL following chemoimmunotherapy but unfortunately succumbed to pseudotumor cerebri complications during induction therapy.© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.
