The first head-to-head comparison of high throughput sequencing (HTS) using immunoSEQ? (Adaptive Biotechnologies and traditional flow cytometry conducted in collaboration with Fred Hutchinson Cancer Research Center and the University of WashingtonDepartment of Laboratory Medicine, demonstrated that immunoSEQ detected minimal residual disease (MRD) in nearly twice the number of patients with the blood cancer T-lineage acute lymphoblastic leukemia/lymphoma (T-ALL) than flow cytometry. The study published in the May 16th issue of Science Translational Medicine
“Minimal residual disease is a major predictor of relapse in blood cancers. Our study results highlight the potential of HTS technology to define lower detection thresholds for MRD that could impact clinical treatment decisions,” explained Harlan Robins, M.D., the corresponding author, Adaptive Biotechnologies co-founder and associate faculty member at the Hutchinson Center. “Improving the ability to consistently detect and track residual disease at a molecular level affords clinicians the ability to predict relapse earlier and improve patient care.”
In the study, immunoSEQ assay and University of Washington’s flow cytometry assay were used to identify the primary cancer clone in 43 patients diagnosed with T-ALL. Each patient then underwent chemotherapy treatment. After 29 days, the two assays were used to detect MRD, the small number of cancer cells that may remain after treatment. HTS was significantly more sensitive than flow cytometry at detecting subsequent minimal residual disease post-treatment. HTS identified MRD in 10 cases missed by flow cytometry (22 vs. 12, respectively). The study also showed that the immunoSEQ platform could detect 1 in 200,000 clones as compared to 1 in 10,000 clones for flow cytometry, representing a 20-fold difference in sensitivity.
Immune profiling
ImmunoSEQ is a breakthrough solution for immune profiling that provides a sensitive, reliable and cost-effective method for researchers to accurately evaluate overall T cell receptor repertoire diversity at a specific point in time to diagnose disease and over a span of time to monitor disease.
“We have clearly demonstrated the power of next-generation immune sequencing for clinical monitoring applications, such as MRD,” explained Adaptive Biotechnologies CEO, Chad Robins. “Adaptive is leading the effort to demonstrate the clinical relevance of high throughput immune profiling for disease detection, monitoring and personalized treatment decisions in cancer and numerous immune disorders.”
Reproducible and reliable results
In addition to its greater sensitivity, HTS offers many advantages over flow cytometry. Since HTS can detect any pre-identified clone and is performed in a centralized lab, it consistently generates reproducible and reliable results regardless of disease type using the same process for disease detection and tracking. In contrast, flow cytometry is specific to a known subset of cancerous surface markers that vary by cancer subtype and uses different processes for identification 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 subject to human error.
The researchers will track clinical outcomes from the 43 patients in this trial to validate the clinical relevance of a lower detection threshold for MRD. They are also working together on a similar trial in a significantly larger population of patients with various forms of leukemia and lymphoma. In addition, the researchers are also running other confirmatory studies around the globe with leading academic institutions and biopharmaceutical companies.
For more information:
Wu D, Sherwood A, Fromm JR, Winter SS, Dunsmore KP, Loh ML, Greisman HA, Sabath DE, Wood BL, Robins H. High-Throughput Sequencing Detects Minimal Residual Disease in Acute T Lymphoblastic Leukemia.
Sci Transl Med16 May 2012: Vol. 4, Issue 134, p. 134ra63 Sci. Transl. Med. DOI: 10.1126/scitranslmed.3003656
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