The applicability of multiparameter flow cytometry for the detection of minimal residual disease using different-from-normal panels to predict relapse in patients with acute myeloid leukemia after allogeneic transplantation

Int J Lab Hematol. 2019 Oct;41(5):607-614. doi: 10.1111/ijlh.13070. Epub 2019 Jun 4.

Abstract

Background: The MRD status detected using multiparameter flow cytometry (MFC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) has crucial prognostic value for patients with acute myeloid leukemia (AML) in morphologic complete remission (CR). We designed a novel panel of antibodies to identify aberrant differentiation/maturation profiles of residual leukemia cells in patients who were not diagnosed at our institution, relapsed with an antigenic shift, or lack leukemia-associated immunophenotypes.

Methods: We compared the MRD status detected using MFC and real-time quantitative polymerase chain reaction (RT-qPCR) in the same 158 bone marrow samples collected from 44 AML patients carrying leukemia-specific fusion genes. The clinical performance of the MFC-based MRD status was analyzed in 168 AML patients who exhibited morphologic CR (135) or active disease (33) before HSCT.

Results: Strong concordance was found between MFC-based and RT-qPCR-based MRD status (κ = 0.868). Among the patients displaying CR, the positive MRD status detected using MFC was correlated with a worse prognosis [HRs (P values) for relapse, event-free survival, and overall survival: 4.83 (<0.001), 2.23 (0.003), and 1.79 (0.049), respectively]; the prognosis was similar to patients with an active disease before HSCT. Patients with a positive MRD before HSCT might experience a benefit from developing chronic graft-vs-host disease.

Conclusions: The assessment of MRD using our self-built different-from-normal AML-MRD detection panel exhibited reliable sensitivity, specificity, and accuracy. In addition, patients with a positive MRD status before transplantation may have higher risk of relapse and worse survival.

Keywords: acute myeloid leukemia; allogeneic stem cell transplantation; minimal residual disease; multiparameter flow cytometry; relapse.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Child
  • Disease-Free Survival
  • Female
  • Flow Cytometry / instrumentation
  • Flow Cytometry / methods*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunophenotyping / methods
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / therapy*
  • Male
  • Middle Aged
  • Neoplasm, Residual / diagnosis*
  • Neoplasm, Residual / genetics
  • Oncogene Proteins, Fusion / genetics
  • Prognosis
  • Recurrence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transplantation, Homologous
  • Young Adult

Substances

  • Oncogene Proteins, Fusion