Date of Graduation
4-2022
Document Type
Thesis (MS)
Program Affiliation
Cancer Biology
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Marina Konopleva, MD PhD
Committee Member
Elias Jabbour, MD
Committee Member
Farhad Ravandi, MD
Committee Member
Koichi Takahashi, MD
Committee Member
Sean Post, PhD
Committee Member
Xuelin Huang, PhD
Abstract
Measurable residual disease (MRD) is highly prognostic for relapse and overall survival (OS) in acute lymphoblastic leukemia (ALL), although many patients with apparent “MRD negativity” by standard assays still relapse. We evaluated the clinical impact of a highly sensitive next-generation sequencing (NGS) MRD assay in 74 adults with ALL undergoing frontline therapy. Among remission samples that were MRD negative by multiparameter flow cytometry (MFC), 46% were MRD positive by the NGS assay. At the time of complete remission (CR), MRD negativity by MFC at a sensitivity of 1x10-4 and NGS at a sensitivity of 1x10-6 was achieved in 66% and 23% of patients, respectively. The 5-year cumulative incidence of relapse (CIR) among patients who achieved MRD negativity by MFC at CR was 29%; in contrast, no patients who achieved MRD negativity by NGS at CR relapsed, and their 5-year OS was 90%. NGS MRD negativity at CR was associated with significantly decreased risk of relapse compared with MRD positivity (5-year CIR: 0% versus 45%, respectively, P=0.04). Among patients who were MRD negative by MFC at the time of CR, detection of low levels of MRD by NGS identified patients who still had a significant risk of relapse (5-year CIR: 39%). Early assessment of MRD using a highly sensitive NGS assay adds clinically relevant prognostic information to standard MFC-based approaches and can identify patients with ALL undergoing frontline therapy who have a very low risk of relapse and excellent long-term survival.
Keywords
residual disease, acute lymphoblastic leukemia, prognosis, MRD, relapse, survival