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Plasma cell-free DNA is a prognostic biomarker for survival in patients with aggressive non-Hodgkin lymphomas

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Abstract

Cell-free DNA (cfDNA) can be released from tumor cells during proliferation and apoptosis; thus, a fraction of the cfDNA in patients with cancer is tumor-derived. However, the prognostic value of cfDNA in aggressive non-Hodgkin lymphoma (NHL) has not been determined. Between March 2017 and April 2019, plasma cfDNA was obtained from 158 patients with aggressive NHL who were registered in a prospective Samsung Medical Center lymphoma cohort (diffuse large B cell lymphoma (DLBCL), n = 51; T cell lymphoma (TCL), n = 51; NK/T cell lymphoma (NKTCL), n = 56). The concentration of cfDNA was estimated in longitudinal samples collected from patients with NHL before and during various chemotherapy regimens. In pretreatment samples, the median cfDNA concentration of all patients with aggressive lymphoma was 13.7 ng/dl (range 1.7–1792), which was significantly higher than that of healthy volunteers (median 7.4 ng, range 3.7–14.4, p < 0.001), and advanced stages showed a higher cfDNA level than earlier stages. Multivariate analysis identified high cfDNA as an independent factor for event-free survival that predicted poor prognosis in DLBCL (hazard ratio [HR] = 5.33, 95% confidence interval [CI] = 1.72–16.52, p = 0.003) and TCL (HR = 2.82, 95% CI = 1.10–7.20, p = 0.030). NKTCL patients with a high level of cfDNA had worse overall survival (HR = 4.71, 95% CI = 1.09–20.35, p = 0.037) compared with those with a low level of cfDNA. In this study, our results suggest the usefulness of pretreatment cfDNA as a prognostic marker for patients with DLBCL, TCL, and NKTCL.

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Funding

This study was supported by the National Research Foundation of Korea (NRF) Grants funded by the Korean Government (MSIT) (2017M3A9G5060264) and NRF Grants funded by the Korean Government (ME) (2017R1D1A1B03028759).

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Author notes

  1. Joon Young Hur and Yeon Jeong Kim contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea

    Joon Young Hur, Sang Eun Yoon, Seok Jin Kim & Won Seog Kim

  2. Division of Hematology and Oncology, Department of Internal Medicine, Hanyang University Guri Hospital, Guri, South Korea

    Joon Young Hur

  3. Samsung Genome Institute Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea

    Yeon Jeong Kim, Woong-Yang Park & Donghyun Park

  4. School of Big Data Science, Data Science Convergence Research Center, Hallym University, Chuncheon, South Korea

    Dae-Soon Son

  5. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea

    Woong-Yang Park

  6. GENINUS Inc, Seoul, South Korea

    Donghyun Park

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  1. Joon Young Hur
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Correspondence to Donghyun Park or Won Seog Kim.

Ethics declarations

The Institutional Review Board at SMC approved this present study (SMC 2016-11-040), and all methods were carried out in accordance with the approved guidelines. All patients provided informed consent before inclusion in this study.

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Electronic supplementary material

Supplemental Figure 1

Distribution of cfDNA according to sex and age (PDF 47 kb)

Supplemental Figure 2

Distribution of cfDNA according to stage in patients with NKTCL and TCL (PDF 49 kb)

Supplemental Figure 3

Correlation of cfDNA and various clinical variables in patients with NHLs (PDF 158 kb)

Supplemental Figure 4

Correlation of cfDNA and various clinical variables in patients with DLBCL (PDF 79 kb)

Supplemental Figure 5

Correlation of cfDNA and various clinical variables in patients with TCL (PDF 86 kb)

Supplemental Figure 6

Correlation of cfDNA and various clinical variables in patients with NKTCL (PDF 75 kb)

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Hur, J.Y., Kim, Y.J., Yoon, S.E. et al. Plasma cell-free DNA is a prognostic biomarker for survival in patients with aggressive non-Hodgkin lymphomas. Ann Hematol 99, 1293–1302 (2020). https://doi.org/10.1007/s00277-020-04008-3

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