Voso Maria Teresa, Guarnera Luca, Lehmann Söhren, Döhner Konstanze, Döhner Hartmut, Platzbecker Uwe, Russell Nigel, Dillon Richard, Thomas Ian, Ossenkoppele Gert, Haferlach Torsten, Vignetti Marco, La Sala Edoardo, Piciocchi Alfonso, Fazi Paola, Ramiro Angela Villaverde, Giménez Laura Tur, Gurnari Carmelo, Bullinger Lars, Hernández-Rivas Jesús María
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
PhD Program in Immunology, Molecular Medicine and Applied Biotechnologies, University of Rome Tor Vergata, Rome, Italy.
Blood. 2025 Jan 9;145(2):234-243. doi: 10.1182/blood.2024026186.
Treatment outcomes for acute promyelocytic leukemia (APL) have improved with the widespread use of targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Our study aimed to validate these data in a large patient cohort, and to redefine prognostic factors. Leveraging the HARMONY Platform, we analyzed 1438 newly diagnosed patients with APL, diagnosed between 1999 and 2022. Patient data derived from the 2 international multicenter Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA)-APL0406 and National Cancer Research Institute (NCRI)-AML17 trials and 4 European registries: the Haemato Oncology Foundation for Adults in the Netherlands, Belgium and Luxembourg (HOVON), AML Study Group (AMLSG), Swedish AML Registry, and Study Alliance Leukemia (SAL). The study cohort included 721 males and 717 females, with a median age of 50.5 years (range, 16-94 years). Of 1309 patients starting therapy, 562 received ATRA-ATO, and 747 idarubicin-based chemotherapy (AIDA-like CHT). Early death (ED) occurred in 85 of 1438 patients (5.9%) at a median of 9 days after APL diagnosis and was independently associated with increasing age and high Sanz risk score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.04-1.08; and OR, 4.65; 95% CI, 2.55-8.51, respectively). The median follow-up was 5.5 years (interquartile range, 3.2-7.5 years). ATRA-ATO regimen was associated with the best outcome, reaching 91% 7-year overall survival (vs 81% for AIDA-like CHT; hazard ratio [HR], 2.14; 95% CI, 1.51-3.05), 89% event-free survival (vs 71% for AIDA-like CHT; HR, 2.72; 95% CI, 2.01-3.69), and 3% relapse (vs 13% for AIDA-like CHT; HR, 4.19; 95% CI, 2.38-7.39; P < .001 for all outcomes). The survival advantage of ATRA/ATO was independent of patients' age, Sanz risk score, and treatment scenario. Our study confirms the superiority of ATRA-ATO over ATRA-chemotherapy in patients with APL. Reducing the risk of ED still represents an unmet medical need, in particular in older patients and in high-risk APL.
随着全反式维甲酸（ATRA）和三氧化二砷（ATO）靶向治疗的广泛应用，急性早幼粒细胞白血病（APL）的治疗效果有所改善。我们的研究旨在在一个大型患者队列中验证这些数据，并重新定义预后因素。利用HARMONY平台，我们分析了1999年至2022年间确诊的1438例新诊断的APL患者。患者数据来自2项国际多中心意大利成人血液学疾病研究组（GIMEMA）-APL0406试验和英国国家癌症研究所（NCRI）-AML17试验，以及4个欧洲登记处：荷兰、比利时和卢森堡成人血液肿瘤基金会（HOVON）、AML研究组（AMLSG）、瑞典AML登记处和白血病研究联盟（SAL）。该研究队列包括721名男性和717名女性，中位年龄为50.5岁（范围16 - 94岁）。在1309例开始治疗的患者中，562例接受了ATRA - ATO治疗，747例接受了基于伊达比星的化疗（类似AIDA的化疗）。1438例患者中有85例（5.9%）发生早期死亡，中位时间为APL诊断后9天，且与年龄增加和高Sanz风险评分独立相关（优势比[OR]，1.06；95%置信区间[CI]，1.04 - 1.08；以及OR，4.65；95% CI，2.55 - 8.51）。中位随访时间为5.5年（四分位间距，3.2 - 7.5年）。ATRA - ATO方案的治疗效果最佳，7年总生存率达到91%（相比类似AIDA的化疗为81%；风险比[HR]，2.14；95% CI，1.51 - 3.05），无事件生存率为89%（相比类似AIDA的化疗为71%；HR，2.72；95% CI，2.01 - 3.69），复发率为3%（相比类似AIDA的化疗为13%；HR，4.19；95% CI，2.38 - 7.39；所有结果P < 0.001）。ATRA/ATO的生存优势与患者年龄、Sanz风险评分和治疗方案无关。我们的研究证实了ATRA - ATO在APL患者中优于ATRA - 化疗。降低早期死亡风险仍然是一项未满足的医疗需求，特别是在老年患者和高危APL患者中。
