Routine Evaluation of Minimal Residual Disease in Myeloma Using Next-Generation Sequencing Clonality Testing: Feasibility, Challenges, and Direct Comparison with High-Sensitivity Flow Cytometry.

The Journal of Molecular Diagnostics : JMD
Caleb HoMaria E Arcila

Abstract

The 2016 International Myeloma Working Group consensus recommendations emphasize high-sensitivity methods for minimal residual disease (MRD) detection, treatment response assessment, and prognostication. Next-generation sequencing (NGS) of IGH gene rearrangements is highly specific and sensitive, but its description in routine clinical practice and performance comparison with high-sensitivity flow cytometry (hsFC) remain limited. In this large, single-institution study including 438 samples from 251 patients, the use of NGS targeting the IGH and IGK genes for clonal characterization and monitoring, with comparison to hsFC, is described. The index clone characterization success rate was 93.6% (235/251), which depended on plasma cell (PC) cellularity, reaching 98% when PC ≥10% and below 80% when PC <5%. A total of 85% of cases were successfully characterized using leader and FR1 primer sets, and most clones showed high somatic hypermutation rates (median, 8.1%). Among monitoring samples from 124 patients, 78.6% (147/187) had detectable disease by NGS. Concordance with hsFC was 92.9% (170/183). Discordant cases encompassed 8 of 124 hsFC MRD+/NGS MRD- patients (6.5%) and 4 of 124 hsFC MRD-/NGS MRD+ patients (3.2%), all with low-lev...Continue Reading

References

Jul 21, 2006·Leukemia·B G M DurieUNKNOWN International Myeloma Working Group
Dec 1, 2011·Blood·Bruno PaivaUNKNOWN PETHEMA/GEM (Programa para el Estudio de la Terapéutica en Hemopatías Malignas/Grupo Español de Mieloma) Cooperative Study G
Dec 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Aaron C LoganDavid B Miklos
Apr 29, 2014·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Aaron C LoganDavid B Miklos
Sep 26, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·H TakamatsuS Nakao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Sequencing

Several sequencing approaches are employed to understand and examine tumor development and progression. These include whole genome as well as RNA sequencing. Here is the latest research on cancer sequencing.