Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia
Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia
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全反式视黄酸/三氧化二砷治疗新诊断的急性早幼粒细胞白血病的长期疗效和安全性。
DOI：
10.1073/pnas.0813280106
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发表时间：
2009-03-03
影响因子：
11.1
通讯作者：
Chen, Zhu
中科院分区：
文献类型：
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作者：
Hu, Jiong;Liu, Yuan-Fang;Chen, Zhu
在短期研究中，全反式视黄酸（ATRA）/三氧化二砷（ATO）联合治疗使新诊断的急性早幼粒细胞白血病（APL）受益，但长期疗效和安全性仍不清楚。自 2001 年 4 月起，我们对 85 名接受 ATRA/ATO 的患者进行了随访，中位随访时间为 70 个月。 80 名患者 (94.1%) 进入完全缓解 (CR)。 Kaplan-Meier 估计所有患者的 5 年无事件生存率 (EFS) 和总生存率 (OS) 分别为 89.2% +/- 3.4% 和 91.7% +/- 3.0%，达到 CR 的患者 (n = 80) 的 5 年无复发生存率 (RFS) 和 OS 分别为 94.8% +/- 2.5% 和 97.4% +/-分别为 1.8%。 ATRA/ATO 后，预后不受初始白细胞计数、不同 PML-RAR α 类型或 FLT3 突变的影响。毒性特征轻微且可逆。没有观察到继发性癌症，并且在最后一次服用 ATRA/ATO 后 24 个月，患者的尿砷浓度远低于安全限度。这些结果表明，在长期随访中，ATRA/ATO 治疗新诊断的 APL 具有高效且毒性最小的特点，这表明 ATRA/ATO 是治疗新发 APL 的潜在一线疗法。
All-trans retinoic acid (ATRA)/arsenic trioxide (ATO) combination-based therapy has benefitted newly diagnosed acute promyelocytic leukemia (APL) in short-term studies, but the long-term efficacy and safety remained unclear. From April 2001, we have followed 85 patients administrated ATRA/ATO with a median follow-up of 70 months. Eighty patients (94.1%) entered complete remission (CR). Kaplan-Meier estimates of the 5-year event-free survival (EFS) and overall survival (OS) for all patients were 89.2% +/- 3.4% and 91.7% +/- 3.0%, respectively, and the 5-year relapse-free survival (RFS) and OS for patients who achieved CR (n = 80) were 94.8% +/- 2.5% and 97.4% +/- 1.8%, respectively. Upon ATRA/ATO, prognosis was not influenced by initial white blood cell count, distinct PML-RAR alpha types, or FLT3 mutations. The toxicity profile was mild and reversible. No secondary carcinoma was observed, and 24 months after the last dose of ATRA/ATO, patients had urine arsenic concentrations well below the safety limit. These results demonstrate the high efficacy and minimal toxicity of ATRA/ATO treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for de novo APL.