Oral arsenic trioxide, all-trans retinoic acid, and ascorbic acid maintenance after first complete remission in acute promyelocytic leukemia: Long-term results and unique prognostic indicators
Oral arsenic trioxide, all-trans retinoic acid, and ascorbic acid maintenance after first complete remission in acute promyelocytic leukemia: Long-term results and unique prognostic indicators
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DOI：
10.1002/cncr.32937
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发表时间：
2020-05-04
期刊：
影响因子：
6.2
通讯作者：
Kwong, Yok-Lam
中科院分区：
文献类型：
--
作者：
Gill, Harinder S.;Yim, Rita;Kwong, Yok-Lam
背景三氧化二砷（As 2 O3）在维持急性早幼粒细胞白血病（APL）首次完全缓解（CR 1）中的作用尚不清楚。（全反式维甲酸[ATRA]/柔红霉素）和巩固（柔红霉素/阿糖胞苷[年龄>= 70岁时省略柔红霉素诱导和巩固治疗]）接受维持治疗，包括ATRA（45毫克/平方米/天），口服三氧化二砷结果在2002年8月1日至2019年7月31日的17年期间，63名男性和66名女性，（中位年龄，46岁[范围，18-82岁]）接受AAA维持治疗，117例患者已经完成。在中位随访100个月（范围，8-215个月）时，17例患者（13%）在CR 1后中位19个月（范围，7-96个月）后首次复发（R1）（血液学，n = 14;分子学，n = 3）。2例R1患者伴有中枢神经系统（CNS）受累。所有患者口服As 2 O3为基础的补救达到CR2。5名患者随后复发并死亡。8例患者在CR 1时死于不相关原因。5年和10年无复发生存率（RFS）分别为89%和85%。5年和10年总生存率（OS）分别为94%和87%。多变量分析显示，较差RFS与FLT 3-ITD（P = 0.005）和CNS受累（P = 0.004）相关，较差OS与治疗相关APL（P = 0.03）、FLT 3-ITD（P = 0.03）和复发（P = 0.03）相关。结论AAA维持CR 1治疗APL是安全的，可提高APL患者的长期生存率。
Background The role of arsenic trioxide (As2O3) in the maintenance of first complete remission (CR1) in acute promyelocytic leukemia (APL) is unclear.Methods A total of 129 consecutive adult patients with APL of all risk categories who achieved CR1 with conventional induction (all-trans retinoic acid [ATRA]/daunorubicin) and consolidation (daunorubicin/cytarabine [induction daunorubicin and consolidation omitted for age >= 70 years]) underwent maintenance comprising ATRA (45 mg/m(2)/day), oral As2O3 (10 mg/day), and ascorbic acid (1 g/day) (AAA) for 2 weeks every 2 months for 2 years.Results Over a 17-year period from August 1, 2002, to July 31, 2019, 63 men and 66 women (median age, 46 years [range, 18-82 years]) received AAA maintenance, which was already completed in 117 patients. At a median follow-up of 100 months (range, 8-215 months), 17 patients (13%) developed first relapse (R1) (hematologic, n = 14; molecular, n = 3) after a median of 19 months (range, 7-96 months) from CR1. Two R1 patients had concomitant central nervous system (CNS) involvement. All patients achieved CR2 with oral As2O3-based salvage. Five patients had a subsequent relapse and died. Eight patients died of unrelated causes while still in CR1. The 5-year and 10-year rates of relapse-free survival (RFS) were 89% and 85%, respectively. The 5-year and 10-year rates of overall survival (OS) were 94% and 87%, respectively. Multivariate analysis showed that inferior RFS was associated with FLT3-ITD (P = .005) and CNS involvement on presentation (P = .004), and inferior OS was associated with therapy-related APL (P = .03), FLT3-ITD (P = .03), and relapse (P = .03). The safety profile was favorable, with no grade 3/4 organ toxicities.Conclusion CR1 maintenance with AAA is safe and results in favorable long-term survival in patients with APL.