Frisch Avraham, Ganzel Chezi, Ofran Yishai, Krayem Baher, Haran Arnon, Vainstein Vladimir, Aumann Shlomzion, Even-Zohar Noa Gross, Nachmias Boaz
Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, and Rappaport Faculty of Medicine-Technion, Haifa, Israel.
The Hematology and Stem Cell Transplantation Department and the Eisenberg R&D Authority, Shaare Zedek Medical Center; Faculty of Medicine, Hebrew University of Jerusalem, Israel.
Eur J Haematol. 2025 Apr;114(4):641-649. doi: 10.1111/ejh.14375. Epub 2024 Dec 30.
Molecular assessment of measurable residual disease (MRD) in NPM1-mutated AML patients is a powerful prognostic tool to identify the risk of relapse. There is limited data regarding MRD-guided decisions against alloSCT in elderly patients and FLT3-ITD co-mutation. We describe the outcome of NPM1-mutated AML patients in whom alloSCT was deferred based on ELN 2017 risk and MRD response. We report a relapse rate of 53% in this group, with a much higher incidence for older than 60 years patients than for younger patients (73% vs. 37%). When comparing outcomes of alloSCT in CR1 to intensive chemotherapy consolidation within each age group, patients over 60 years and patients with FLT3-ITD co-mutation had significantly lower RFS with intensive consolidation. Yet, in all subgroups, the lower RFS did not translate into OS difference, suggesting that relapsed NPM1 patients can often be salvaged and consequently achieve long-term remission. Our study supports the use of MRD response along with FLT3-ITD status in the decision to use post-remission therapy. We demonstrate that older patients and patients with FLT3-ITD-mutated AML have a high relapse rate but can be salvaged, leading to long-term survival.
对NPM1突变的急性髓系白血病（AML）患者进行可测量残留病（MRD）的分子评估是识别复发风险的有力预后工具。关于老年患者和FLT3-ITD共突变患者中基于MRD指导决定是否进行异基因造血干细胞移植（alloSCT）的数据有限。我们描述了根据2017年欧洲白血病网络（ELN）风险和MRD反应推迟进行alloSCT的NPM1突变AML患者的结局。我们报告该组的复发率为53%，60岁以上患者的复发率远高于年轻患者（73%对37%）。在比较每个年龄组中首次完全缓解（CR1）时alloSCT与强化化疗巩固治疗的结局时，60岁以上患者和伴有FLT3-ITD共突变的患者接受强化巩固治疗后的无复发生存期（RFS）显著更低。然而，在所有亚组中，较低的RFS并未转化为总生存期（OS）差异，这表明复发的NPM1患者通常可以挽救并因此实现长期缓解。我们的研究支持在决定缓解后治疗时使用MRD反应以及FLT3-ITD状态。我们证明老年患者和FLT3-ITD突变的AML患者复发率高，但可以挽救，从而实现长期生存。
