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高危急性早幼粒细胞白血病（APL）治疗仍具有挑战性，早期死亡率和复发率较高。最近的证据表明三氧化二砷（ATO）联合ATRA治疗低危APL预后良好，先前的初步研究表明ATO+ATRA+吉妥珠单抗奥佐米星（GO）治疗高危APL亚组患者有效。
SWOG设计了一项更大型的2期研究来证实这一联合疗法治疗高危APL的安全性和有效性。主要目标是：1）评估早期（6周）死亡率；2）评估3年的持续完全缓解（CRR）。
【方法】
研究纳入成人新诊断高危APL（WBC ≥10k/uL）患者。诱导疗法包括：ATRA（45mg/m2/天，第1天使用，直至CR）；ATO（0.15mg/kg/天，第10天使用，直至CR）；GO（9 mg/m2，第1天使用）。达到CR的患者接受两个疗程的ATO巩固治疗，然后接受ATRA +柔红霉素2个疗程和GO2个疗程。随后接受ATRA+6-MP+甲氨蝶呤维持治疗一年。
【结果】
从2008年至2013年，共纳入73名患者并用于评估毒性。中位年龄为46.5岁，52%为女性，48%为男性。62名患者完成计划的诱导疗法，48名患者完成计划的巩固疗法。初始治疗6周内有6/73（11%）名患者早期死亡（95% CI 6-21%），支持摒弃无效假设（30%早期死亡率）。
诱导期间最常见的治疗中出现的3-4级不良反应包括：发热性嗜中性粒细胞减少症（33%），AST/ALT升高（12%），缺氧/分化综合征（11%），高血糖症（11%），头痛（11%），QTc延长（11%）。59名接受巩固治疗的患者中，最常见的治疗相关3-4级不良反应包括：发热性嗜中性粒细胞减少症（52%），头痛（14%），疲劳（14%）和恶心（12%）。目前正在进行CRR疗效分析。
【结论】
ATO+ ATRA + GO联合疗法治疗高危APL患者具有安全性且耐受性良好，早期死亡率可接受。3年的CCR评估尚未成熟。
英文摘要
Safety and tolerability of the combination of ATRA + arsenic trioxide (ATO) + gemtuzumab ozogamicin (GO) in high-risk acute promyelocytic leukemia (APL):Initial report of the SWOG/Alliance/ECOG S0535 trial. (Abstract No: 7016)
SessionType: Poster Discussion Session
Background:High-risk APL remains a therapeutic challenge, with significant rates of early mortality and relapse. Recent evidence confirmed excellent outcomes in low-risk APL with the combination of ATO and ATRA (Lo-Coco, NEJM 2013), and a previous pilot study indicated the efficacy of a combination of ATO + ATRA + GO in asubset of high-risk APL (Ravandi, JCO 2009). SWOG designed a larger phase 2study to confirm the safety and efficacy of this combination in high-risk APL.Primary Objectives: 1) assessment of early (6 week) death rate; 2) assessment of 3-year continuous complete remission (CCR)
Methods:Adult patients with newly diagnosed high-risk APL (WBC ≥ 10k/uL) were eligible. Induction therapy consisted of: ATRA (45 mg/m2/day) - day 1 until CR; ATO (0.15mg/kg/day) – day 10 until CR; GO 9 mg/m2- day 1.Patients in CR received consolidation with ATO x 2 cycles, followed by ATRA +daunorubicin x 2 cycles, followed by GO x 2 cycles. Subsequent maintenancetherapy consisted of ATRA + 6-MP + methotrexate for up to 1 year.
Results:From 2008 to 2013, 73 patients were enrolled and evaluable for toxicity. Medianage was 46.5 years, with 52% females and 48% males. Sixty-two (85%) patients completed induction therapy as planned, and 48 patients (66%) completed all planned consolidation. Six of 73 patients (11%) died within 6 weeks of treatment initiation (95% confidence interval 6-21%), supporting rejection of the null hypothesis (30% early death rate). The most common treatment-emergent grade 3-4 adverse events (AE) during induction included: febrile neutropenia(33%), AST/ALT elevation (12%), hypoxia / differentiation syndrome (11%), hyperglycemia (11%), headache (11%), prolonged QTc (11%).Amongst 59 patients receiving consolidation, the most common treatment-emergent grade 3-4 AEs included: febrile neutropenia (52%), headache (14%), fatigue(14%), and nausea (12%). The efficacy analysis of CCR is ongoing.
Conclusions:The combination of ATO + ATRA + GO appears safe andwell-tolerated in patients with high-risk APL, with an acceptable early mortality rate. 3-year CCR assessment is not yet mature.
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