Modeling early treatment response in AML from cell-free tumor DNA

被引:2
作者
Wang, Dantong [1 ,2 ]
Rausch, Christian [3 ,4 ]
Buerger, Simon A. [3 ]
Tschuri, Sebastian [3 ]
Rothenberg-Thurley, Maja [3 ]
Schulz, Melanie [1 ,2 ]
Hasenauer, Jan [2 ,5 ,6 ]
Ziemann, Frank [3 ,4 ]
Metzeler, Klaus H. [7 ]
Marr, Carsten [1 ,2 ]
机构
[1] Inst AI Hlth, Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany
[2] Tech Univ Munich, Ctr Math, D-85748 Garching, Germany
[3] Univ Hosp LMU, Dept Med 3, Lab Leukemia Diagnost, Munich, Germany
[4] German Canc Consortium DKTK, Partner Sites Munich, Dresden, Germany
[5] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Computat Hlth Ctr, D-85764 Neuherberg, Germany
[6] Rhein Friedrich Wilhelms Univ Bonn, Fac Math & Nat Sci, D-53115 Bonn, Germany
[7] Univ Hosp Leipzig UHL, Dept Hematol & Cell Therapy, D-04103 Leipzig, Germany
基金
欧洲研究理事会;
关键词
ACUTE MYELOID-LEUKEMIA; RESIDUAL DISEASE; CHEMOTHERAPY; MUTATIONS; EVOLUTION; DIAGNOSIS; RELAPSE; RISK;
D O I
10.1016/j.isci.2023.108271
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Monitoring disease response after intensive chemotherapy for acute myeloid leukemia (AML) currently requires invasive bone marrow biopsies, imposing a significant burden on patients. In contrast, cell-free tumor DNA (ctDNA) in peripheral blood, carrying tumor-specific mutations, offers a less-invasive assessment of residual disease. However, the relationship between ctDNA levels and bone marrow blast kinetics remains unclear. We explored this in 10 AML patients with NPM1 and IDH2 mutations undergoing initial chemotherapy. Comparison of mathematical mixed-effect models showed that (1) inclusion of blast cell death in the bone marrow, (2) transition of ctDNA to peripheral blood, and (3) ctDNA decay in peripheral blood describes kinetics of blast cells and ctDNA best. The fitted model allows prediction of residual bone marrow blast content from ctDNA, and its scaling factor, representing clonal heterogeneity, correlates with relapse risk. Our study provides precise insights into blast and ctDNA kinetics, offering novel avenues for AML disease monitoring.
引用
收藏
页数:21
相关论文
empty
未找到相关数据