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Updated: Jul 26, 2025

VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
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Relapse Timing Is Associated With Distinct Evolutionary Dynamics in Diffuse Large B-Cell Lymphoma.

Laura K Hilton1,2, Henry S Ngu1, Brett Collinge1,3

  • 1Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|June 15, 2023
PubMed
Summary

Outcomes for refractory or relapsed diffuse large B-cell lymphoma (DLBCL) depend on relapse timing. Late relapses often represent distinct, chemotherapy-naïve disease, impacting treatment strategies.

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Area of Science:

  • Hematology
  • Oncology
  • Genomics

Background:

  • Diffuse large B-cell lymphoma (DLBCL) has a high cure rate, but outcomes for refractory or relapsed DLBCL (rrDLBCL) are poor, especially with early relapse.
  • Previous studies identified relapse-enriched features, but direct comparison of serial biopsies is needed to understand rrDLBCL evolutionary dynamics.

Purpose of the Study:

  • To confirm the relationship between relapse timing and outcomes after second-line therapy in DLBCL.
  • To determine the evolutionary dynamics underlying this relationship in rrDLBCL.

Main Methods:

  • Examined outcomes in 221 DLBCL patients treated with second-line therapy and autologous stem-cell transplantation (ASCT).
  • Performed molecular characterization, including whole-genome/exome sequencing, on serial biopsies from 129 patients.

Main Results:

  • Outcomes were superior for late relapse (>2 years) compared to primary refractory (<9 months) or early relapse (9-24 months).
  • Diagnostic and relapse biopsies showed concordance in cell-of-origin and subgroup, but increasing mutation divergence over time.
  • Late relapses shared few mutations with diagnostic counterparts, indicating branching evolution; convergent evolution of key genes was observed in divergent tumors.

Conclusions:

  • Late relapses in DLBCL may represent genetically distinct, chemotherapy-naïve disease.
  • These findings have significant implications for optimizing patient management strategies in rrDLBCL.