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细胞遗传学治疗反应对急性髓系白血病长期生存的影响

Impact of Cytogenetic Response to Therapy on Long-Term Survival in Acute Myeloid Leukemia.

作者信息

Hanna John, Zabor Emily C, Albliwi Moath, El-Asmar Jessica, Nurse Daniel P, Bawwab Ameed, Abuamsha Hasan, Abu-Farsakh Yomna, Batah Heya, Rauf Asad, Nakitandwe Joy, Bosler David S, Jain Akriti G, Molina John C, Balderman Sophia, Singh Abhay, Gerds Aaron T, Mukherjee Sudipto, Sobecks Ronald M, Advani Anjali S, Carraway Hetty E, Astbury Caroline, Mustafa Ali Moaath K

机构信息

Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA.

Department of Quantitative Health Sciences, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA.

出版信息

Am J Hematol. 2025 Sep;100(9):1577-1589. doi: 10.1002/ajh.70000. Epub 2025 Jul 11.

Abstract

Prognostication in acute myeloid leukemia (AML) relies on clinical, molecular, and cytogenetic factors. In this retrospective study, we examined the impact of different levels of cytogenetic response on overall survival (OS) and event-free survival (EFS) in AML. Among 973 adult AML patients treated at Cleveland Clinic (5/2017-9/2023), 563 patients had baseline cytogenetic data and post-treatment response assessment available. Based on baseline and response cytogenetic status, patients were categorized into: normal to normal (NL-Cy to NL-Cy, n = 221, 39%), normal or abnormal to gain (NL/Abnl-Cy to Gain-Cy, n = 46, 8.2%), abnormal to persistent (Abnl-Cy to Persistent-Cy, n = 81, 14%), abnormal to partial response (Abnl-Cy to Partial-Cy, n = 20, 3.6%), and abnormal to complete response (Abnl-Cy to NL-Cy, n = 195, 35%). Landmark analysis was used to account for post-treatment assessments. The cohort had a median age of 62 years (interquartile range: 52-69), 256 females (45%), 90% were White, and median follow-up of 45.8 months (range: 0.73-191.3). The median OS and hazard ratios (HRs) from multivariable regression analysis were as follows: NL-Cy to NL-Cy: 37 months (95% CI: 27-91), HR = reference; NL/Abnl-Cy to Gain-Cy: 14 months (95% CI: 8.6-30), HR = 1.5 (95% CI: 0.99-2.39); Abnl-Cy to Persistent-Cy: 13 months (95% CI: 12-18), HR = 1.61 (95% CI: 1.13-2.31); Abnl-Cy to Partial-Cy: 25 months (95% CI: 14-NC), HR = 0.76 (95% CI: 0.39-1.49); and Abnl-Cy to NL-Cy: 27 months (95% CI: 19-101), HR = 1.25 (95% CI: 0.93-1.68) (p = 0.038). Achieving cytogenetic remission, complete or partial, was associated with better survival outcomes. These findings highlight the importance of monitoring cytogenetic responses to inform treatment decisions and support integrating cytogenetic response into risk-adapted, personalized AML management strategies.

摘要

急性髓系白血病(AML)的预后评估依赖于临床、分子和细胞遗传学因素。在这项回顾性研究中,我们研究了不同水平的细胞遗传学反应对AML患者总生存期(OS)和无事件生存期(EFS)的影响。在克利夫兰诊所接受治疗的973例成年AML患者(2017年5月至2023年9月)中,563例患者有基线细胞遗传学数据和治疗后反应评估。根据基线和反应时的细胞遗传学状态,患者被分为:正常至正常(NL-Cy至NL-Cy,n = 221,39%)、正常或异常至获得性改变(NL/Abnl-Cy至Gain-Cy,n = 46,8.2%)、异常至持续性改变(Abnl-Cy至Persistent-Cy,n = 81,14%)、异常至部分缓解(Abnl-Cy至Partial-Cy,n = 20,3.6%)以及异常至完全缓解(Abnl-Cy至NL-Cy,n = 195,35%)。采用地标性分析来考虑治疗后的评估情况。该队列的中位年龄为62岁(四分位间距:52 - 69岁),女性256例(45%),90%为白人,中位随访时间为45.8个月(范围:0.73 - 191.3个月)。多变量回归分析得出的中位OS和风险比(HRs)如下:NL-Cy至NL-Cy:37个月(95%CI:27 - 91),HR = 参考值;NL/Abnl-Cy至Gain-Cy:14个月(95%CI:8.6 - 30),HR = 1.5(95%CI:0.99 - 2.39);Abnl-Cy至Persistent-Cy:13个月(95%CI:12 - 18),HR = 1.61(95%CI:1.13 - 2.31);Abnl-Cy至Partial-Cy:25个月(95%CI:14 - NC),HR = 0.76(95%CI:0.39 - 1.49);Abnl-Cy至NL-Cy:27个月(95%CI:19 - 101),HR = 1.25(95%CI:0.93 - 1.68)(p = 0.038)。实现细胞遗传学缓解,无论是完全缓解还是部分缓解,都与更好的生存结果相关。这些发现突出了监测细胞遗传学反应以指导治疗决策以及支持将细胞遗传学反应纳入风险适应性、个性化AML管理策略的重要性。

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