As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO–based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA–anthracycline for low-/intermediate-risk patients, or ATRA-ATO–anthracycline versus ATRA–anthracycline–cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of –5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI –0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan–Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA–chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

作为全反式视黄酸（ATRA）和三氧化二砷（ATO）被广泛用于治疗急性早幼粒细胞白血病（APL），降低毒性成为研究的热点。在这里，我们评估了处于不同风险的APL患者是否可以用ATO替代或减少化疗。在基于ATRA-ATO的诱导疗法获得完全缓解后，将患者随机（1：1）分为ATO组和非ATO组，以巩固治疗：对于低/中危患者或ATRA-ATO与ATRA-蒽环类抗生素高危患者使用ATO蒽环类药物对比ATRA蒽环类药物阿糖胞苷。主要终点是评估3年时的无病生存期（DFS），非劣质性余量为–5％；855名患者入组，中位随访时间为54.9 mo，在3年时可以评估755名患者中的658名。在ATO小组中，为96。1％（319/332）达到了3年DFS，而非ATO组为92.6％（302/326）。差异为3.45％（95％CI –0.07至6.97），证实了自卑感（P <0.001）。使用Kaplan–Meier方法，在ATO组中估计的7年DFS为95.7％（95％CI 93.6至97.9），在非ATO组中为92.6％（95％CI 89.8至95.4）（P = 0.066）。关于次要终点，ATO的7年累积复发率（CIR）显着低于非ATO组（2.2％[95％CI 1.1至4.2]）（6.1％[95％CI 3.9至9.5]） ，P = 0.011）。此外，在巩固期间，ATO组的3至4级血液学毒性显着降低。因此，在巩固和替代化疗的情况下，ATRA-ATO均不逊于ATRA化疗（https://www.clinicaltrials.gov/，NCT01987297）。