By Melissa Badamo November 6, 2023
A recent study established a novel strategy for analyzing measurable residual disease (MRD) in T-cell acute lymphoblastic leukemia (T-ALL) using next generation sequencing (NGS) of T-cell receptor (TCR)β and TCRγ clonotypes.
This strategy is “potentially translatable to all T-cell derived hematological malignancies,” according to the study’s authors. The results were presented by Nicholas Young, PhD, of the Ohio State University Wexner Medical Center, at the 2023 Society for Immunotherapy of Cancer Annual Meeting.
“The objective of this work was to use a pilot training set of retrospective data from T-ALL patients to propose a putative clinical test for MRD detection,” wrote Dr. Young, noting that MRD levels in ALL are associated with significantly improved overall survival and event-free survival after induction treatment.
In this study, NGS TCRβ and TCRγ clonotypes were collected from 43 healthy adults aged 18-35, including bone marrow aspirates pretreatment and post-induction therapy. According to pretreatment analysis of these clonotypes, the expansion of multiple clones was found to be putative biomarkers for an individualized panel.
In the healthy control cohort, the TCRβ and TCRγ clones were not expressed at a frequency greater than 0.08% and represented putative neoplastic lymphoblasts. Using all productive rearrangements that were expressed more than 3% of the total TCRβ or TCRγ sequences in the treatment-naive sample, all samples qualified for longitudinal MRD testing.
These panels were used to evaluate the corresponding post-induction treatment samples. The study defined positive MRD detection as “identification of at least one of the pretreatment neoplastic clones in the top 50 TCRβ or TCRγ rearrangements.”
“This strategy identified MRD in post-induction treatment samples that were both [multiparametric flow cytometry (mpFC)] positive and negative, which suggests enhanced sensitivity of MRD detection,” Dr. Young concluded.
Reference
Young N. Novel analysis strategy of T-cell receptor NGS data to develop patient-specific clonotype panels and detect minimal residual disease (MRD) in T-cell acute lymphoblastic leukemia (T-ALL). Abstract #186. Presented at the 2023 Society for Immunotherapy of Cancer Annual Meeting; November 1-5, 2023; San Diego, California.
Original Source: Novel Analysis Strategy Detects MRD in T-cell Acute Lymphoblastic Leukemia (T-ALL) | Blood Cancers Today