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利用可测量残留病制定急性髓系白血病的移植策略:一项为期20年的单中心观察研究

Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation.

作者信息

Buccisano Francesco, Palmieri Raffaele, Piciocchi Alfonso, Maurillo Luca, Del Principe Maria Ilaria, Paterno Giovangiacinto, Soddu Stefano, Cerretti Raffaella, De Angelis Gottardo, Mariotti Benedetta, Irno Consalvo Maria Antonietta, Conti Consuelo, Fraboni Daniela, Divona Mariadomenica, Ottone Tiziana, Lavorgna Serena, Panetta Paola, Voso Maria Teresa, Arcese William, Venditti Adriano

机构信息

Department of Biomedicine and Prevention, University Tor Vergata of Roma, 00133 Rome, Italy.

Centro Dati Fondazione GIMEMA, 00100 Rome, Italy.

出版信息

Cancers (Basel). 2021 Mar 3;13(5):1083. doi: 10.3390/cancers13051083.

Abstract

Measurable residual disease (MRD) is increasingly employed as a biomarker of quality of complete remission (CR) in intensively treated acute myeloid leukemia (AML) patients. We evaluated if a MRD-driven transplant policy improved outcome as compared to a policy solely relying on a familiar donor availability. High-risk patients (adverse karyotype, FLT3-ITD) received allogeneic hematopoietic cell transplant (alloHCT) whereas for intermediate and low risk ones (CBF-AML and NPM1-mutated), alloHCT or autologous SCT was delivered depending on the post-consolidation measurable residual disease (MRD) status, as assessed by flow cytometry. For comparison, we analyzed a matched historical cohort of patients in whom alloHCT was delivered based on the sole availability of a matched sibling donor. Ten-years overall and disease-free survival were longer in the MRD-driven cohort as compared to the historical cohort (47.7% vs. 28.7%, = 0.012 and 42.0% vs. 19.5%, = 0.0003). The favorable impact of this MRD-driven strategy was evident for the intermediate-risk category, particularly for MRD positive patients. In the low-risk category, the significantly lower CIR of the MRD-driven cohort did not translate into a survival advantage. In conclusion, a MRD-driven transplant allocation may play a better role than the one based on the simple donor availability. This approach determines a superior outcome of intermediate-risk patients whereat in low-risk ones a careful evaluation is needed for transplant allocation.

摘要

可测量残留病(MRD)越来越多地被用作强化治疗的急性髓系白血病(AML)患者完全缓解(CR)质量的生物标志物。我们评估了与仅依赖于合适供体可用性的策略相比,基于MRD的移植策略是否能改善预后。高危患者(不良核型、FLT3-ITD)接受异基因造血细胞移植(alloHCT),而对于中低危患者(CBF-AML和NPM1突变型),根据流式细胞术评估的巩固治疗后可测量残留病(MRD)状态进行alloHCT或自体造血干细胞移植(SCT)。为了进行比较,我们分析了一个匹配的历史队列患者,这些患者仅根据匹配同胞供体的可用性进行alloHCT。与历史队列相比,基于MRD的队列中10年总生存率和无病生存率更长(47.7%对28.7%,P = 0.012;42.0%对19.5%,P = 0.0003)。这种基于MRD的策略对中危组的有利影响很明显,特别是对于MRD阳性患者。在低危组中,基于MRD的队列中显著较低的复发率并未转化为生存优势。总之,基于MRD的移植分配可能比基于简单供体可用性的分配发挥更好的作用。这种方法决定了中危患者的更好预后,而对于低危患者,移植分配需要仔细评估。

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