High frequency of identical clonal immunoglobulin DNA in pre-treatment tumor and plasma from untreated patients with HIV-associated lymphoma: prospective multicenter trial of the AIDS malignancies consortium (AMC 064)

Leuk Lymphoma. 2017 Dec;58(12):2939-2942. doi: 10.1080/10428194.2017.1317095. Epub 2017 May 16.

Abstract

Patients with HIV are at increased risk for developing B-cell lymphomas likely due in part to chronic antigen stimulation leading to clonal immunoglobulin (Ig) gene rearrangements. Next-generation sequencing (NGS)-based identification of circulating Ig clonotypes has not been well-characterized in HIV-related lymphomas. The AIDS Malignancies Consortium (AMC) enrolled 51 untreated patients with HIV-related B-cell lymphomas and analyzed paired tumor/plasma specimens for Ig clonotypes using an NGS approach (AMC064, NCT00981097). Lymphoma-specific clonotypes (>5% frequency) were identified in 83% (33/40) of tumor specimens. Results from paired tumor/plasma specimens showed identical circulating clonotypes in the plasma from 97% (32/33) of patients. High International Prognostic Index (IPI) scores of 3-4 among patients with B-cell lymphoma correlated with higher lymphoma molecules/million diploid genomes in the plasma compared with lower IPI scores of 0-2, median 77335 vs. 6876, p = .005. Further studies are merited to determine whether plasma clonal Ig DNA is prognostic in HIV-related lymphomas.

Keywords: DNA; HIV; Immunoglobulin; Lymphoma; clones.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Clonal Evolution / genetics*
  • DNA, Circular*
  • Female
  • Gene Frequency*
  • Gene Rearrangement
  • Humans
  • Immunoglobulins / genetics*
  • Lymphoma, AIDS-Related / blood
  • Lymphoma, AIDS-Related / diagnosis
  • Lymphoma, AIDS-Related / genetics*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Young Adult

Substances

  • Biomarkers
  • DNA, Circular
  • Immunoglobulins

Associated data

  • ClinicalTrials.gov/NCT00981097