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三氧化二砷序贯全反式维甲酸联合蒽环类药物治疗急性早幼粒细胞白血病具有出色的长期治愈率。

Sequential Treatment of Arsenic Trioxide Followed by All Trans Retinoic Acid with Anthracyclines has Excellent Long-Term Cure in Acute Promyelocytic Leukemia.

作者信息

Devadas Santhosh Kumar, Jain Hasmukh, Bagal Bausaheb, Sengar Manju, Dangi Uma, Khattry Navin, Amre Pratibha, Patkar Nikhil, Subramaniam P G, Nair Reena, Menon Hari

机构信息

Department of Medical Oncology, Ramaiah Medical College and Hospital, Bengaluru, India.

Department of Medical Oncology, Tata Memorial Center, Lower Parel, Mumbai, India.

出版信息

Indian J Hematol Blood Transfus. 2021 Jan;37(1):30-36. doi: 10.1007/s12288-020-01311-x. Epub 2020 Jun 26.

Abstract

Acute promyelocytic leukemia (APL) remains the most curable myeloid leukemia made feasible through effective use of two differentiating agents, all trans retinoic acid (ATRA) and arsenic trioxide (ATO) with or without chemotherapy (CT). However, early morbidity and mortality remains a problem. With the objective of reducing early death a strategy of sequential induction ATO followed by consolidation ATRA in combination with CT was adopted by our group. The long-term outcomes of patient of APL treated on this sequential approach at our center was analyzed. In this retrospective analysis of prospectively maintained database consecutive adult patients with APL irrespective of their Sanz risk group were treated using a protocol of ATO (10 mg IV infusion over 3 h daily for 45 days) in the first phase followed by ATRA (45 mg/m for 60 days) in combination with Daunorubicin (60 mg/m for 3 days × 3 cycles) in second phase. All patients received maintenance ATRA (45 m/m for 15 days every 3 months) for a period of 18 months in phase 3. Patients were monitored for cytogenetic and molecular responses after phase 1 and 2. All patients were followed up for toxicity, event free and overall survival. 131 consecutive patients were treated in this study. At a median follow up of 60 months, 84.81% patients are alive with an overall event free survival (EFS) of 77.82%. Sanz low risk patients fared better (85%) versus intermediate and high-risk patients who had a 76% EFS. Proportion of patients alive at last follow up were 100% in Sanz low risk group and 82% in intermediate and high-risk group. The sequential schedule showed excellent tolerance and toxicity profile when treating newly diagnosed APL. The long-term follow-up data shows comparable if not better survival compared with the published real-world data and this has been consistent across all risk group.

摘要

急性早幼粒细胞白血病(APL)仍然是最可治愈的髓系白血病,通过有效使用两种分化剂,即全反式维甲酸(ATRA)和三氧化二砷(ATO),无论是否联合化疗(CT),都可实现治愈。然而,早期发病率和死亡率仍然是一个问题。为了降低早期死亡率,我们团队采用了一种序贯诱导策略,即先使用ATO,然后使用ATRA联合CT进行巩固治疗。分析了在我们中心采用这种序贯方法治疗的APL患者的长期结局。在这项对前瞻性维护数据库的回顾性分析中,连续的成年APL患者,无论其Sanz风险组如何,在第一阶段使用ATO方案(每天静脉输注10mg,持续3小时,共45天),随后在第二阶段使用ATRA(45mg/m²,持续60天)联合柔红霉素(60mg/m²,3天×3个周期)。所有患者在第三阶段接受维持性ATRA治疗(45mg/m²,每3个月15天),为期18个月。在第1阶段和第2阶段后监测患者的细胞遗传学和分子反应。对所有患者进行毒性、无事件生存期和总生存期的随访。本研究共治疗了131例连续患者。中位随访60个月时,84.81%的患者存活,总无事件生存期(EFS)为77.82%。Sanz低风险患者的情况更好(85%),而中高风险患者的EFS为76%。最后一次随访时存活患者的比例在Sanz低风险组为100%,在中高风险组为82%。序贯方案在治疗新诊断的APL时显示出极好的耐受性和毒性特征。长期随访数据显示,与已发表的真实世界数据相比,生存率即使不比其更好也相当,并且在所有风险组中都是一致的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/836e/7900266/0135590e7831/12288_2020_1311_Fig1_HTML.jpg

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