Gill Harinder, Raghupathy Radha, Hou Hsin-An, Cheng-Hong Tsai Xavier, Tantiworawit Adisak, Ooi Melissa G, Gan Gin-Gin, Wong Chieh-Lee, Yim Rita, Chin Lynn, Lee Paul, Li Vivian W K, Au Lester, Zhang Qi, Leung Garret M K, Wu Tony K Y, Lee Carmen Y Y, Chng Wee-Joo, Tien Hwei-Fang, Kumana Cyrus R, Kwong Yok-Lam
Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Blood Adv. 2025 Feb 25;9(4):862-876. doi: 10.1182/bloodadvances.2024014999.
The Acute Promyelocytic Leukemia (APL) Asian Consortium analyzed a contemporaneous cohort of newly diagnosed patients with APL treated with and without frontline arsenic trioxide (ATO) in 6 centers. The objectives were to define the impact of ATO on early deaths and relapses and its optimal positioning in the overall treatment strategy. In a 21.5-year period, 324 males and 323 females at a median age of 45.5 years (range, 18.1-91.8; low/intermediate risk, n = 448; high risk, n = 199) were treated. Regimens included frontline all-trans retinoic acid (ATRA)/chemotherapy and maintenance with/without ATO (n = 436), ATRA/IV-ATO/chemotherapy (ATRA/IV-ATO; n = 61), and ATRA/oral-ATO/ascorbic acid with ATO maintenance (oral-AAA; n = 150). The ATRA/chemotherapy group had significantly more frequent early deaths within 60 days (8.3% vs 3.3%; P = .05), inferior 60-day survival (91.7% vs 98.4%/96%; P < .001), inferior 5-year relapse-free survival (RFS; 76.9% vs 92.8%/97.8%; P < .001), and inferior 5-year overall survival (OS; 84.6% vs 91.4%/92.3%; P = .03) than ATO-containing groups (ATRA/IV-ATO and oral-AAA). The addition of oral-ATO maintenance partly mitigated the inferior 5-year RFS resulting from the omission of ATO during induction (ATRA/chemotherapy/non-ATO maintenance vs ATRA/chemotherapy/ATO maintenance vs ATRA/IV-ATO vs oral-AAA, 71.1% vs 87.9% vs 92.8% vs 97.8%; P < .001). The favorable survival impacts of ATO were observed in all risk groups. In conclusion, ATO decreased early deaths, improved 60-day survival, and resulted in significantly superior RFS and OS. This trial was registered at www.clinicaltrials.gov as #NCT04251754.
急性早幼粒细胞白血病（APL）亚洲协作组分析了6个中心新诊断的APL患者的同期队列，这些患者接受或未接受一线三氧化二砷（ATO）治疗。目的是确定ATO对早期死亡和复发的影响及其在整体治疗策略中的最佳定位。在21.5年的时间里，共治疗了324名男性和323名女性，中位年龄为45.5岁（范围18.1 - 91.8岁；低/中危，n = 448；高危，n = 199）。治疗方案包括一线全反式维甲酸（ATRA）/化疗以及有或无ATO维持治疗（n = 436）、ATRA/静脉注射ATO/化疗（ATRA/IV - ATO；n = 61）和ATRA/口服ATO/维生素C并维持使用ATO（口服AAA；n = 150）。与含ATO的组（ATRA/IV - ATO和口服AAA）相比，ATRA/化疗组在60天内的早期死亡更频繁（8.3%对3.3%；P = 0.05），60天生存率更低（91.7%对98.4%/96%；P < 0.001），5年无复发生存率（RFS）更低（76.9%对92.8%/97.8%；P < 0.001），5年总生存率（OS）更低（84.6%对91.4%/92.3%；P = 0.03）。添加口服ATO维持治疗部分减轻了诱导期遗漏ATO导致的较差的5年RFS（ATRA/化疗/非ATO维持治疗对ATRA/化疗/ATO维持治疗对ATRA/IV - ATO对口服AAA，71.1%对87.9%对92.8%对97.8%；P < 0.001）。在所有风险组中均观察到ATO对生存的有利影响。总之，ATO降低了早期死亡，改善了60天生存率，并导致显著更好的RFS和OS。该试验已在www.clinicaltrials.gov上注册，编号为#NCT04251754。
