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异基因移植前的疾病负担与移植后早期微小残留病相结合可预测急性髓系白血病患者的生存情况。

Combination of disease burden before allogeneic transplantation and early post-transplant minimal residual disease predicts survival in patients with acute myeloid leukemia.

作者信息

Stock Claudia Núñez-Torrón, Chillón Carlos Jiménez, Hernández Clara López, Moro Fernando Martín, Palomanes Juan Marquet, Villaespesa Miguel Piris, de Abia Alejandro Luna, Santiago Ernesto Roldán, Martín Eulalia Rodríguez, Rodríguez Anabelle Chinea, Gutiérrez Valentín García, Jiménez Gemma Moreno, Jiménez Javier López, Puente Pilar Herrera

机构信息

Departamento de Hematología y Hemoterapia, Hospital Universitario Infanta Sofía, Avenida Paseo de Europa, Madrid, 34 28702, Spain.

Universidad Alcalá de Henares, Madrid, Spain.

出版信息

Ann Hematol. 2025 Apr;104(4):2469-2481. doi: 10.1007/s00277-025-06325-x. Epub 2025 Apr 25.

Abstract

The burden disease before allogeneic transplantation (HSCT) or the early post-transplant minimal residual disease (MRD) are both predictive parameters for relapse and post-HSCT survival in acute myeloid leukemia (AML). Nonetheless, the combination of both can provide more accurate information to identify high risk patients. To analyze the impact of pre-HSCT disease burden (MRD- vs. MRD + vs. active disease (AD), the early post-transplant MRD (posMRD + vs. posMRD-), and the combination of both pre- and post-HSCT disease status of the post-HSCT outcomes in AML patients. We retrospectively analyzed 173 patients with AML who underwent HSCT in a single institution, patients were classified according to pre-HSCT disease status, and post-HSCT MRD. MRD was measured by multiparameter flow cytometry using a cut-off of 0.1% for MRD+. The post-HSCT outcomes were analyzed based on the pre-transplant status, post-transplant status, and by combining both parameters. Patients with AD and MRD + before HSCT had worse 3y-event free (EFS) and overall survival (OS) than MRD- patients, due to a higher cumulative incidence of relapse (CIR). Also, patients with posMRD + had worse outcomes than posMRD- group. In the combined analysis, patient with MRD-/posMRD- had the best EFS and OS (3y-EFS 66.5%, 3y-OS 70.0%). Patients with MRD+/posMRD- have worse prognosis (3y-EFS 39.0%, 3y-OS 54.0%) and specially the group with AD/MRD- (3y-EFS 13.5%, 3y-OS 22.0%) and posMRD + regardless pre-HSCT disease status(3y-EFS 26.5%, 3y-OS 28.0%) had dismal OS and EFS. The combination of pre-HSCT disease burden and post-HSCT MRD measurements help us for identifying high-risk subgroups. Any level of pre-transplant disease (MRD+, and especially patients with active AD) is a risk factor, even when MRD- was achieved post-transplant. Patients with post-transplant MRD + also had an adverse prognosis. These should be target groups for implementing tailored pre- and post-transplant strategies to improve outcomes.

摘要

异基因造血干细胞移植(HSCT)前的疾病负担或移植后早期的微小残留病(MRD)都是急性髓系白血病(AML)复发和HSCT后生存的预测参数。尽管如此,两者结合可以提供更准确的信息来识别高危患者。为了分析HSCT前疾病负担(MRD- 与MRD + 与活动性疾病(AD))、移植后早期MRD(阳性MRD + 与阳性MRD-)以及HSCT前后疾病状态的组合对AML患者HSCT后结局的影响。我们回顾性分析了在单一机构接受HSCT的173例AML患者,根据HSCT前疾病状态和HSCT后MRD对患者进行分类。MRD通过多参数流式细胞术测量,MRD + 的临界值为0.1%。基于移植前状态、移植后状态以及结合这两个参数分析HSCT后的结局。HSCT前患有AD和MRD + 的患者3年无事件生存率(EFS)和总生存率(OS)比MRD- 患者差,这是由于复发累积发生率(CIR)更高。此外,阳性MRD + 的患者结局比阳性MRD- 组差。在综合分析中,MRD-/阳性MRD- 的患者EFS和OS最佳(3年EFS 66.5%,3年OS 70.0%)。MRD+/阳性MRD- 的患者预后较差(3年EFS 39.0%,3年OS 54.0%),特别是AD/MRD- 组(3年EFS 13.5%,3年OS 22.0%)以及无论HSCT前疾病状态如何的阳性MRD + 组(3年EFS 26.5%,3年OS 28.0%)的OS和EFS都很差。HSCT前疾病负担和HSCT后MRD测量的结合有助于我们识别高危亚组。任何水平的移植前疾病(MRD +,尤其是患有活动性AD的患者)都是一个危险因素,即使移植后达到MRD- 也是如此。移植后MRD + 的患者预后也较差。这些应该是实施定制的移植前和移植后策略以改善结局的目标群体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46c1/12053072/61842595892a/277_2025_6325_Fig1_HTML.jpg

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