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June 25, 2019
Sponsored by
Agilent

Error-Corrected Sequencing to Detect Measurable Residual Disease in Post-Transplant MDS Cases

GenomeWebinar

Associate Professor, Pathology & Immunology; Section Head, Hematopathology;
Washington University School of Medicine in St. Louis

Global Product Manager, Genomics and Diagnostics Group,
Agilent Technologies

This webinar focuses on measurable residual disease (MRD) monitoring in post allogeneic hematopoietic cell transplantation (alloHCT) myelodysplastic syndrome (MDS) cases. 

Standard sequencing-based technologies have a limited ability to detect low-abundance mutations due to the inherit error rate of the sequencing technology and pre-analytic errors associated with PCR amplification and sequencing library construction. This approach is generally limited to the detection of mutations with variant allele frequencies (VAFs) of greater than 2.5 percent. 

Our speaker, Eric Duncavage, discusses an approach his team used to address this issue, which used HaloPlex HS error-corrected sequencing coupled with high-coverage depths that allowed them to detect VAFs as low as 0.03%, or one tumor cell in ~1,600 cells. 

Dr. Duncavage’s team applied HaloPlex HS to bone marrows collected prior to and 30 days after transplant in 86 MDS patients by targeting previously identified somatic mutations. They found that 32 of 86 cases (37 percent) had at least one mutation at day 30 post-alloHCT with a maximum mutation VAF greater than 0.5 percent (equivalent to 1 mutant cell in 100 cells).

Dr. Duncavage details the study, which found that cases who progressed had a higher maximum mutation VAF 30 days after transplant compared to those who did not. Multivariate analysis confirmed that the detection of a mutation with a VAF greater than 0.5 percent 30 days after alloHCT was associated with an increased risk of progression and decreased progression-free survival. 

For Research Use Only. Not for use in diagnostic procedures.

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