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治疗相关性继发性急性髓系白血病:一种具有不良预后的独特高危急性髓系白血病亚组。

Treated secondary acute myeloid leukemia: a distinct high-risk subset of AML with adverse prognosis.

作者信息

Boddu Prajwal, Kantarjian Hagop M, Garcia-Manero Guillermo, Ravandi Farhad, Verstovsek Srdan, Jabbour Elias, Borthakur Gautam, Konopleva Marina, Bhalla Kapil N, Daver Naval, DiNardo Courtney D, Benton Christopher B, Takahashi Koichi, Estrov Zeev, Pierce Sherry R, Andreeff Michael, Cortes Jorge E, Kadia Tapan M

机构信息

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.

出版信息

Blood Adv. 2017 Jul 19;1(17):1312-1323. doi: 10.1182/bloodadvances.2017008227. eCollection 2017 Jul 25.

Abstract

Secondary acute myeloid leukemia (s-AML) includes therapy-related AML and AML evolving from antecedent hematological disorder (AHD). s-AML arising after treating AHD likely represents a prognostically distinct, high-risk disease category. In this study, treated s-AML (ts-AML) was defined by: (1) prior diagnosis of myelodysplasia, myeloproliferative neoplasm, or aplastic anemia and (2) at least 1 therapy for that diagnosis. ts-AML was categorized by age (< or ≥60 years), and each cohort assessed for response rates and overall survival (OS) on various treatment regimens. Survival outcomes were compared against other high-risk prognostic subsets. Results showed that complete response and 8-week mortality rates were 32% and 27% in the younger, and 24% and 19% in the older age groups, respectively. There was a significant OS difference within s-AML based on prior treatment of AHD (ie, ts-AML vs s-AML with untreated AHD, 4.2 vs 9.2 months; < .001). Survival in ts-AML was poor across both cohorts (younger and older, 5 and 4.7 months, respectively). In younger AML, survival was significantly inferior in ts-AML when compared with deletion 5/7, TP53, 3q abnormality, and therapy-related AML groups (median, 5 vs 7.9, 7.8, 7.9, and 11.2 months, respectively; < .01). Additional adverse karyotype within ts-AML was associated with even worse outcomes (OS range, 1.6-2.8 months). ts-AML represents a very high-risk category, even in younger AML patients. s-AML should be further classified to describe ts-AML, an entity less responsive to currently applied treatment approaches. Future AML trial designs should accommodate ts-AML as a distinct subgroup.

摘要

继发性急性髓系白血病(s-AML)包括治疗相关的AML和由前驱血液系统疾病(AHD)演变而来的AML。在治疗AHD后发生的s-AML可能代表一种预后明显不同的高危疾病类别。在本研究中,治疗相关性s-AML(ts-AML)定义为:(1)既往诊断为骨髓增生异常综合征、骨髓增殖性肿瘤或再生障碍性贫血,以及(2)针对该诊断至少进行过1次治疗。ts-AML按年龄(<或≥60岁)分类,每个队列评估不同治疗方案的缓解率和总生存期(OS)。将生存结果与其他高危预后亚组进行比较。结果显示,较年轻年龄组的完全缓解率和8周死亡率分别为32%和27%,较年长年龄组分别为24%和19%。基于AHD的既往治疗情况,s-AML患者的OS存在显著差异(即ts-AML与未治疗AHD的s-AML相比,分别为4.2个月和9.2个月;P<0.001)。两个队列(较年轻和较年长)的ts-AML患者生存期均较差(分别为5个月和4.7个月)。在较年轻的AML患者中,与5/7号染色体缺失、TP53、3q异常以及治疗相关AML组相比,ts-AML患者的生存期明显较差(中位生存期分别为5个月与7.9个月、7.8个月、7.9个月和11.2个月;P<0.01)。ts-AML患者额外的不良核型与更差的预后相关(OS范围为1.6 - 2.8个月)。即使在较年轻的AML患者中,ts-AML也代表一个非常高危的类别。s-AML应进一步分类以描述ts-AML,这是一种对当前应用的治疗方法反应较差的实体。未来AML试验设计应将ts-AML作为一个独特的亚组纳入考虑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18ed/5727976/a24fc74b957f/advances008227absf1.jpg

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