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急性早幼粒细胞白血病:全反式维甲酸和三氧化二砷治疗相关并发症综述

Acute Promyelocytic Leukemia: Review of Complications Related to All-Trans Retinoic Acid and Arsenic Trioxide Therapy.

作者信息

Ghiaur Alexandra, Doran Cristina, Gaman Mihnea-Alexandru, Ionescu Bogdan, Tatic Aurelia, Cirstea Mihaela, Stancioaica Maria Camelia, Hirjan Roxana, Coriu Daniel

机构信息

Department of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022338 Bucharest, Romania.

Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.

出版信息

Cancers (Basel). 2024 Mar 15;16(6):1160. doi: 10.3390/cancers16061160.

Abstract

The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA). The PML::RARA fusion is a molecular target for all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Therapies based on ATRA plus ATO have excellent outcomes in terms of complete remission rates, overall survival, and achievement of deep and durable molecular responses with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of distinctive toxicities, such as differentiation syndrome, liver toxicity, QT interval prolongation, and neurotoxicity. Rigorous monitoring of patients' clinical evolution is indispensable for identifying and addressing each complication. The objective is to maintain an equilibrium between treatment-induced adverse events and therapeutic efficacy. This paper focused on non-hematologic complications associated with the combination of ATRA and ATO. Additionally, we discuss late-onset complications of this therapy. In summary, the majority of treatment-related adverse events are manageable, self-limiting, and reversible. More so, there seems to be a lower incidence rate of secondary neoplasms compared to standard chemotherapy. However, further research is required to assess how the ATRA plus ATO regimen affects the emergence of additional comorbidities.

摘要

急性早幼粒细胞白血病(APL)的标志是早幼粒细胞白血病基因与维甲酸受体α基因(PML::RARA)形成特征性融合转录本。PML::RARA融合是全反式维甲酸(ATRA)和三氧化二砷(ATO)的分子靶点。基于ATRA加ATO的疗法在完全缓解率、总生存率以及实现深度持久的分子反应且复发率极低方面具有出色的疗效。然而,尽管ATRA和ATO联合使用的血液学毒性低于标准化疗,但其使用会伴有一系列独特的毒性,如分化综合征、肝毒性、QT间期延长和神经毒性。对患者临床病情的严格监测对于识别和处理每种并发症必不可少。目标是在治疗引起的不良事件和治疗效果之间保持平衡。本文重点关注与ATRA和ATO联合使用相关的非血液学并发症。此外,我们还讨论了这种疗法的迟发性并发症。总之,大多数与治疗相关的不良事件是可控的、自限性的且可逆的。更重要的是,与标准化疗相比,继发性肿瘤的发生率似乎较低。然而,需要进一步研究来评估ATRA加ATO方案如何影响其他合并症的出现。

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