Long-Term Outcome of Relapsed Acute Promyelocytic Leukemia Treated With Oral Arsenic Trioxide-Based Reinduction and Maintenance Regimens: A 15-Year Prospective Study
Long-Term Outcome of Relapsed Acute Promyelocytic Leukemia Treated With Oral Arsenic Trioxide-Based Reinduction and Maintenance Regimens: A 15-Year Prospective Study
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DOI：
10.1002/cncr.31327
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发表时间：
2018-06-01
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;Yim, Rita;Kwong, Yok-Lam
背景技术背景：对于急性早幼粒细胞白血病（APL）第二次完全缓解（CR2）的患者，最佳缓解后策略尚未确定。方法：口服三氧化二砷（As 2 O3）为基础的方案在管理APL患者CR2的作用进行了检查。结果：73例APL患者首次复发（R1）进行了研究。口服As 2 O3为基础的reinduction导致一致的CR2，无论以前的As 2 O3暴露。所有患者均在CR2接受口服As 2 O3为基础的维持治疗。在中位随访94个月（范围，9-205个月）时，43例患者（58.9%）仍处于CR2，49例（67.1%）已完成计划的2年CR2维持治疗，使用全反式维甲酸、口服As 2 O3和抗坏血酸。再诱导和维持治疗耐受性良好。1 ~ 2级头痛20例（27.4%）。35例患者发生了肝毒性，均为转氨酶升高（47.9%; 1级和2级，n = 26; 3级和4级，n = 9）。3例患者出现自限性QTc延长。10年无白血病生存率为56.8%。30例患者发生R2。口服As 2 O3为基础的再诱导导致CR 3 27例（90%）。CR 3后策略包括自体造血干细胞移植和口服As 2 O3维持。在CR 3后30个月（范围，3-166个月）随访时，11例患者仍处于CR 3。R1队列的5年和10年总生存率分别为79.5%和67.3%。既往接受口服As 2 O3维持治疗的CR 1患者是无白血病生存率较低的唯一风险因素。15例患者发生中枢神经系统受累，其中5例存活。口服As 2 O3治疗期间复发是中枢神经系统受累的唯一显著危险因素。结论：对于复发APL患者，尽管反复暴露于As 2 O3，As 2 O3仍然有效。口服As 2 O3维持是CR2缓解后的有效策略。(C)2018美国癌症协会
BACKGROUND: For patients who have acute promyelocytic leukemia (APL) in second complete remission (CR2), optimal postremission strategies remain undefined. METHODS: The role of an oral arsenic trioxide (As2O3)-based regimen in the management of patients who had APL in CR2 was examined. RESULTS: Seventy-three patients with APL in first relapse (R1) were studied. Oral As2O3-based reinduction resulted uniformly in CR2, irrespective of previous As2O3 exposure. All patients received oral As2O3-based maintenance in CR2. At a median follow-up of 94 months (range, 9-205 months), 43 patients (58.9%) were still in CR2, and 49 (67.1%) had finished the planned 2-year CR2 maintenance with all-trans retinoic acid, oral As2O3, and ascorbic acid. Reinduction and maintenance treatments were well tolerated. Grade 1 and 2 headache occurred in 20 patients (27.4%). Hepatotoxicity, all in the form of transaminitis, occurred in 35 patients (47.9%; grade 1 and 2, n = 26; grade 3 and 4, n = 9). Three patients had self-limiting QTc prolongation. The 10-year leukemia-free survival rate was 56.8%. Thirty patients developed R2. Oral As2O3-based reinduction led to CR3 in 27 patients (90%). Post-CR3 strategies included autologous hematopoietic stem cell transplantation and oral As2O3 maintenance. At a post-CR3 follow-up of 30 months (range, 3-166 months), 11 patients were still in CR3. The 5-year and 10-year overall survival rates in the R1 cohort were 79.5% and 67.3%, respectively. Prior receipt of oral As2O3 maintenance in CR1 was the only risk factor for inferior leukemia-free survival. Central nervous system involvement occurred in 15 patients, including 5 who remained alive. Relapse during oral As2O3 therapy was the only significant risk factor for central nervous system involvement. CONCLUSIONS: For patients with relapsed APL, As2O3 remained effective despite repeated As2O3 exposures. Oral As2O3 maintenance was an effective postremission strategy for CR2. (C) 2018 American Cancer Society.