Divion of Hematology, Cardarelli Hospital, Naples, Italy.
Hematology Unit, S. Eugenio Hospital, Rome, Italy.
Expert Opin Pharmacother. 2022 Jan;23(1):117-127. doi: 10.1080/14656566.2021.1961744. Epub 2021 Aug 5.
Until the late 1980s, acute promyelocytic leukemia (APL) was the most rapidly fatal leukemia; however, nowadays, it is a curable disease with survival rates exceeding 90-95%. The improvement of APL outcome is mainly due to two agents, which target the typical translocation t(15;17) and its fusion transcript α responsible for initiating and maintaining the disease: all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). The story of APL represents a pioneering model for the development of precision medicine and curative chemotherapy-free approaches for acute leukemia.
The authors examine the major advances in the treatment of patients with APL focusing on three different eras: 1) the pre-ATRA era; 2) the ATRA era; 3) the ATO era.
The combination of ATRA and ATO is effective and curative for the majority of APL patients. It has been approved for low/intermediate risk cases while an experimental trial with a minimal addition of chemotherapy for high-risk ones is ongoing. Disease relapse is infrequent and can be cured with ATRA-ATO rechallenging, with or without subsequent transplantation depending on the interval between complete remission and relapse. New therapeutic landscapes contemplate the use of an oral chemo-free ATRA-ATO combination, implementing treatment as outpatient care, thus increasing quality of life and decreasing medical costs.
直到 20 世纪 80 年代末，急性早幼粒细胞白血病（APL）是最致命的白血病；然而，如今，它是一种可治愈的疾病，存活率超过 90-95%。APL 预后的改善主要归功于两种靶向典型易位 t（15；17）及其融合转录本 α 的药物，这些药物负责启动和维持疾病：全反式维甲酸（ATRA）和三氧化二砷（ATO）。APL 的故事代表了精准医学和无化疗治疗急性白血病的开创性模式。
作者检查了治疗 APL 患者的主要进展，重点关注三个不同的时代：1）ATRA 前时代；2）ATRA 时代；3）ATO 时代。
ATRA 和 ATO 的联合使用对大多数 APL 患者有效且可治愈。它已被批准用于低/中危病例，而一项针对高危病例的最小添加化疗的实验性试验正在进行中。疾病复发并不常见，用 ATRA-ATO 再挑战可以治愈，是否随后进行移植取决于完全缓解和复发之间的间隔。新的治疗前景包括使用口服无化疗 ATRA-ATO 联合治疗，实施门诊护理，从而提高生活质量并降低医疗费用。
