Predicting Cancer Relapse Improved by High-Throughput DNA Sequencing

Researchers have shown that high-throughput sequencing (HTS) detects the earliest known signs of potential cancer relapse faster and in nearly twice the number of leukemia patients as flow cytometry, the current gold standard for detecting minimal residual disease (MRD).

Specifically, the emerging technology using HTS of lymphoid receptor genes was applied to the diagnosis of T-lineage acute lymphoblastic leukemia/lymphoma. The collaborative study, led by scientists at the Fred Hutchinson Cancer Research Center (Hutchinson Center; Seattle, WA, USA), compared the effectiveness of the two methods to detect MRD, a major predictor of cancer relapse, in 43 patients diagnosed with acute T lymphoblastic leukemia, which is most common in children under age 7.

The results showed that by sequencing patient T-cell receptor genes before and 29 days after chemotherapy, their presence in the blood could be measured precisely and provided a more accurate prediction of leukemia relapse. HTS detected MRD in 22 patients, whereas MRD was detected in only 12 patients by flow cytometry, currently the primary method for detecting MRD in the United States.

These and additional results of this study, which represents the first use of HTS to detect MRD in a clinical trial setting, found HTS to be at least 20 times more sensitive than flow cytometry in detecting MRD.

“Our research indicates that HTS offers many advantages over flow cytometry,” said Harlan Robins, PhD, associate member of the Hutchinson center. “Since HTS can detect any preidentified clone and is performed in a centralized lab, it consistently generates reproducible and reliable results regardless of cancer type, using the same process for disease detection and tracking. Furthermore, HTS is highly automated, cost-effective, and objective, whereas flow cytometry is more time consuming, relies on the skill of the operator, and is therefore subject to human error,” explained Robins.

“The ability to predict disease relapse sooner with high-throughput sequencing would give hematologists the option to treat cancer recurrence earlier, offering a greater chance of survival. Longer term, this technology potentially also could be used to initially diagnose leukemia and lymphoma much earlier than we can today,” added Dr. Robbins.

Dr. Robins and colleagues had adapted traditional high-throughput technology to specifically sequence only variable regions of T- and B-cell receptor genes. The Hutchinson Center has patents pending on core technologies, licensed exclusively to Adaptive Biotechnologies (Seattle, WA, USA), that were employed in conjunction with HTS used for this study.

The results of the study were reported in the May 16, 2012, issue of the journal Science Translational Medicine.

Related Links:
Fred Hutchinson Cancer Research Center
Adaptive Biotechnologies
University of Washington