液体活检
肿瘤科
淋巴瘤
循环肿瘤DNA
活检
内科学
微小残留病
医学
病理
癌症
白血病
作者
Leo Meriranta,Amjad Alkodsi,Annika Pasanen,Maija Lepistö,Parisa Mapar,Yngvild Nuvin Blaker,Judit Jørgensen,Marja-Liisa Karjalainen-Lindsberg,Idun Fiskvik,Lars Tore Gyland Mikalsen,Matias I. Autio,Magnus Björkholm,Mats Jerkeman,Øystein Fluge,Peter Brown,Sirkku Jyrkkiö,Harald Holte,Esa Pitkänen,Pekka Ellonen,Sirpa Leppä
出处
期刊:Blood
[American Society of Hematology]
日期:2021-12-21
卷期号:139 (12): 1863-1877
被引量:13
标识
DOI:10.1182/blood.2021012852
摘要
Inadequate molecular and clinical stratification of the patients with high-risk diffuse large B-cell lymphoma (DLBCL) is a clinical challenge hampering the establishment of personalized therapeutic options. We studied the translational significance of liquid biopsy in a uniformly treated trial cohort. Pretreatment circulating tumor DNA (ctDNA) revealed hidden clinical and biological heterogeneity, and high ctDNA burden determined increased risk of relapse and death independently of conventional risk factors. Genomic dissection of pretreatment ctDNA revealed translationally relevant phenotypic, molecular, and prognostic information that extended beyond diagnostic tissue biopsies. During therapy, chemorefractory lymphomas exhibited diverging ctDNA kinetics, whereas end-of-therapy negativity for minimal residual disease (MRD) characterized cured patients and resolved clinical enigmas, including false residual PET positivity. Furthermore, we discovered fragmentation disparities in the cell-free DNA that characterize lymphoma-derived ctDNA and, as a proof-of-concept for their clinical application, used machine learning to show that end-of-therapy fragmentation patterns predict outcome. Altogether, we have discovered novel molecular determinants in the liquid biopsy that can noninvasively guide treatment decisions.
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