Comprehensive Evaluation And Validation Of A Next-Generation Sequencing Assay For Minimal Residual Disease Detection In T-Lymphoblastic Leukemia/Lymphoma

Introduction: Detection of minimal residual disease (MRD) in T-lymphoblastic leukemia/lymphoma (T-ALL) has been used in post-therapy monitoring and outcome prediction. Currently, multi-color flow cytometry is widely used for MRD detection with limit of detection (LOD) of 0.1 to 0.01% depending on the clinical implementation. However, flow cytometry assays require extensive training and experience for accurate interpretation and standardization is challenging. Next generation sequencing (NGS) assays with panels targeting the inherent polymorphism of the immunoglobulin genes have been applied for MRD detection in B cell neoplasms, including an assay for myeloma and B-ALL MRD detection developed by Adaptive Biotechnologies (Seattle, WA) that was granted FDA approval for clinical testing. We have published a similar approach for T-ALL MRD detection using the polymorphic T-cell receptor (TCR) genes. These assays offer higher sensitivity, easier standardization, and more objective interpretation. Here we present our comprehensive evaluation and validation of a T-ALL MRD assay using the Adaptive Biotechnologies immunoSEQ kit for potential clinical application.