Measurable residual disease testing by next generation sequencing is more accurate compared with multiparameter flow cytometry in adults with B-cell acute lymphoblastic leukemia

Cancer Lett. 2024 Aug 28:598:217104. doi: 10.1016/j.canlet.2024.217104. Epub 2024 Jul 4.

Abstract

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).

Keywords: Acute lymphoblastic leukemia; Measurable residual disease; Multi-parameter flow cytometry; Next generation sequencing; Transplant.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Flow Cytometry* / methods
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Male
  • Middle Aged
  • Neoplasm, Residual*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / diagnosis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / mortality
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Young Adult