Circulating tumor DNA by high-throughput sequencing of T cell receptor monitored treatment response and predicted treatment failure in T cell lymphomas

Int J Lab Hematol. 2021 Oct;43(5):1041-1049. doi: 10.1111/ijlh.13498. Epub 2021 Mar 18.

Abstract

Introduction: Next-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. Studies for T cell lymphoma are limited.

Methods: We explored whether this technology is applicable to T cell lymphoma with different subtypes and assessed its performance in clinical settings.

Results: Thirty tumor and 74 blood samples were analyzed in our study. Malignant clone was identified in 23 of the 30 (76.7%) tumor samples through high-throughput sequencing (HTS) combined with PCR. We detected the same tumor clone in plasma in 18out of the 23 (78.3%) patients. Circulating tumor DNA fraction correlated with lactate dehydrogenase (LDH) (r = .52, P = .017), high level of ctDNA predicted treatment failure (P = .0003) and there was a trend patients with high ctDNA burden would have poorer PFS Furthermore, ctDNA changed in concordance with clinical outcome and was more sensitive than PET/CT. Also, recurrence of ctDNA was an important clue for relapse.

Conclusion: In conclusion, our study indicated that ctDNA monitoring was suitable for T cell lymphoma. High level of pretreatment ctDNA was a poor prognosis factor and changes of ctDNA correlated well with clinical courses and was sensitive to find early relapse.

Keywords: circulating tumor DNA; high throughput sequencing; peripheral T cell lymphoma.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Circulating Tumor DNA / genetics*
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lymphoma, T-Cell / diagnosis
  • Lymphoma, T-Cell / genetics*
  • Lymphoma, T-Cell / therapy
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Receptors, Antigen, T-Cell / genetics*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA
  • Receptors, Antigen, T-Cell