Prognostic Impact of Unsupervised Early Assessment of Bulk and Leukemic Stem Cell Measurable Residual Disease in Acute Myeloid Leukemia

Author:

Canali Alban1ORCID,Vergnolle Inès1ORCID,Bertoli Sarah234ORCID,Largeaud Laetitia134ORCID,Nicolau Marie-Laure1ORCID,Rieu Jean-Baptiste1ORCID,Tavitian Suzanne2ORCID,Huguet Françoise2ORCID,Picard Muriel2ORCID,Bories Pierre2ORCID,Vial Jean Philippe5ORCID,Lechevalier Nicolas5ORCID,Béné Marie Christine6ORCID,Luquet Isabelle1ORCID,Mansat-De Mas Véronique134ORCID,Delabesse Eric134ORCID,Récher Christian234ORCID,Vergez François134ORCID

Affiliation:

1. 1Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France.

2. 2Service d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France.

3. 3Université Toulouse III Paul Sabatier, Toulouse, France.

4. 4Cancer Research Center of Toulouse, UMR1037 INSERM, ERL5294 CNRS, Toulouse, France.

5. 5Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.

6. 6Laboratoire d'Hématologie, CHU de Nantes, Nantes, CRCI²NA INSERM UMR1307, CNRS UMR 6075, France.

Abstract

Abstract Purpose: Acute myeloid leukemias (AML) are clonal diseases that develop from leukemic stem cells (LSC) that carry an independent prognostic impact on the initial response to induction chemotherapy, demonstrating the clinical relevance of LSC abundance in AML. In 2018, the European LeukemiaNet published recommendations for the detection of measurable residual disease (Bulk MRD) and suggested the exploration of LSC MRD and the use of multiparametric displays. Experimental Design: We evaluated the performance of unsupervised clustering for the post-induction assessment of bulk and LSC MRD in 155 patients with AML who received intensive conventional chemotherapy treatment. Results: The median overall survival (OS) for Bulk+ MRD patients was 16.7 months and was not reached for negative patients (HR, 3.82; P < 0.0001). The median OS of LSC+ MRD patients was 25.0 months and not reached for negative patients (HR, 2.84; P = 0.001). Interestingly, 1-year (y) and 3-y OS were 60% and 39% in Bulk+, 91% and 52% in Bulk-LSC+ and 92% and 88% in Bulk-LSC−. Conclusions: In this study, we confirm the prognostic impact of post-induction multiparametric flow cytometry Bulk MRD in patients with AML. Focusing on LSCs, we identified a group of patients with negative Bulk MRD but positive LSC MRD (25.8% of our cohort) with an intermediate prognosis, demonstrating the interest of MRD analysis focusing on leukemic chemoresistant subpopulations.

Funder

Centre Hospitalier Universitaire de Toulouse

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

Reference39 articles.

1. Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rγc-deficient mice;Sarry;J Clin Invest,2011

2. Stem cell concepts renew cancer research;Dick;Blood,2008

3. Human acute myeloid leukemia CD34+/CD38− progenitor cells have decreased sensitivity to chemotherapy and Fas-induced apoptosis, reduced immunogenicity, and impaired dendritic cell transformation capacities;Costello;Cancer Res,2000

4. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region;Ishikawa;Nat Biotechnol,2007

5. Targeting acute myeloid leukemia by dual inhibition of PI3K signaling and Cdk9-mediated Mcl-1 transcription;Thomas;Blood,2013

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3