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急性髓系白血病缓解后治疗:我们是否已准备好采用个体化治疗方法?

Post-remission therapy in acute myeloid leukemia: Are we ready for an individualized approach?

机构信息

Section of Hematology Oncology, Department of Medicine and Comprehensive Cancer Center, University of Chicago, Chicago, IL, USA.

Section of Hematology Oncology, Department of Medicine and Comprehensive Cancer Center, University of Chicago, Chicago, IL, USA.

出版信息

Best Pract Res Clin Haematol. 2019 Dec;32(4):101102. doi: 10.1016/j.beha.2019.101102. Epub 2019 Oct 18.

Abstract

Recent advances in remission induction treatment strategies for acute myeloid leukemia (AML) have improved the rates of complete remission (CR) and overall survival (OS), owing to a concerted effort to tailor therapies toward specific AML subtypes. However, without effective post-remission therapy, most patients will relapse. The extent to which post-remission therapies is individualized in the current paradigm is quite varied. Core binding factor (CBF) AML is typically treated with post-remission high-dose cytarabine (HiDAC) without allogeneic hematopoietic stem cell transplantation (HSCT), whereas those with intermediate or adverse-risk cytogenetics are treated with post-remission cytarabine followed by allogeneic HSCT in CR1 when feasible. A lack of clarity regarding the proper dosing of post-remission cytarabine has made consensus building on dosing and schedule a challenge. CBF AML benefits most from high-dose cytarabine (HiDAC), and dasatinib appears promising as an adjunct for those for KIT-mutated CBF AML. Other than series using CPX-351 or lomustine in older adults, multiagent chemotherapy approaches have resulted in excess toxicity without a survival benefit. Neither hypomethylating agents nor gemtuzumab ozogamicin have shown a material OS benefit. Targeted agents such as FLT3 inhibitors and IDH1/IDH2 inhibitors show potential for the patients who harbor these druggable targets, but few data are available. Many studies evaluating post-remission strategies to target AML in the MRD-positive state are already underway, and these remain a promising area of investigation.

摘要

近年来,急性髓系白血病(AML)缓解诱导治疗策略的进展提高了完全缓解(CR)和总生存率(OS),这是因为人们齐心协力针对特定的 AML 亚型定制治疗方法。然而,如果没有有效的缓解后治疗,大多数患者将复发。在当前的模式下,缓解后治疗在多大程度上个体化差异很大。核心结合因子(CBF)AML 通常采用缓解后高剂量阿糖胞苷(HiDAC)治疗,而不进行异基因造血干细胞移植(HSCT),而那些具有中间或不良风险细胞遗传学的患者在 CR1 时接受缓解后阿糖胞苷治疗,然后在可行时进行异基因 HSCT。缓解后阿糖胞苷的适当剂量缺乏明确性,使得在剂量和方案方面达成共识具有挑战性。CBF AML 最受益于高剂量阿糖胞苷(HiDAC),达沙替尼似乎是 KIT 突变的 CBF AML 的辅助治疗有前途的药物。除了在老年人中使用 CPX-351 或洛莫司汀的系列研究外,多药化疗方法的毒性增加,但没有生存获益。去甲基化剂和 gemtuzumab ozogamicin 均未显示出明显的 OS 获益。针对携带这些可治疗靶点的患者的靶向药物,如 FLT3 抑制剂和 IDH1/IDH2 抑制剂等具有潜力,但可用数据很少。目前已有许多研究正在评估针对 MRD 阳性状态的 AML 的缓解后策略,这仍然是一个很有前途的研究领域。

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