Minimal residual disease

Individualized insights to monitor disease progression

For patients diagnosed with acute myeloid leukemia (AML), which is the second most common type of leukemia, monitoring for measurable, or minimal residual disease (MRD) is a critical component of establishing prognosis and predicting therapeutic response. MRD testing performed at diagnosis as well as after treatment, which can include hematopoietic stem cell transplant, provides physicians key information to:

  • Refine outcome prediction and inform choice of post-remission therapy.
  • Identify impending relapse.
  • Monitor post-hematopoietic stem cell transplant remission status.
  • Objectively assess a deeper remission status beyond the recommended 5% morphology cutoff.

Cytogenic findings typically revealed through diagnostic testing are most often used to understand disease prognosis. Among patients with genetic alterations, those with an NPM1 mutation in the absence of FLT3-ITD are associated with more favorable prognoses. Identification of NPM1 can help evaluate MRD and therapeutic response following treatment.

Full-spectrum MRD testing in one laboratory

The Molecular Hematopathology Laboratory at Mayo Clinic has developed several MRD evaluations that align with guidelines published by the National Comprehensive Cancer Network (NCCN)1 and European LeukemiaNet (ELN). 2

Our NPM1Q MRD test is a combination test that includes a highly sensitive quantitative reverse transcription polymerase chain reaction (RT-PCR) assay that detects and quantifies the most common types of NPM1 variations (A, B, and D) on the messenger RNA transcript level; and a DNA-based qualitative NPM1 exon 11 mutation screening by fragment analysis that detects all altered forms in AML.

The implementation of complementary testing platforms translates into a combined testing approach for MRD that enables detection of essentially all NPM1 mutations reported in AML, including the rare types.

Key testing

NPM1Q | Nucleophosmin (NPM1) Mutation Analysis, Varies

Advantages

  • Serves as a leukemia-specific marker of MRD monitoring.
  • Offers prognostic insights in newly diagnosed AML patients with normal karyotype and no FLT3-ITD.
  • Performs testing on both DNA and RNA.
    • An RNA-based, sensitive quantitative reverse transcription real-time polymerase chain reaction (RT-PCR) that detects and quantifies the most common NPM1 mutation types (A, B, D) on the messenger RNA transcript level.
    • A DNA-based, qualitative NPM1 exon, 11 mutation-screening by fragment analysis that detects essentially all altered forms reported in AML, including the rare non-A, B, D forms.

Additional testing

IN16Q | CBFB-MYH11 Inversion(16), Quantitative Detection and Minimal Disease Risk Monitoring, qRT-PCR, Varies

Advantages

  • Highly sensitive quantitative assay for the detection of inv(16)(p13.1q22) or t(16;16)(p13.1;q22) CBFB-MYH11 gene fusion.

T821Q | RUNX1-RUNX1T1 Translocation (8;21), Minimal Residual Disease Monitoring, Quantitative, Varies

Advantages

  • Highly sensitive quantitative assay for the detection of translocation t(8;21)(q22;q22); RUNX1-RUNX1T1 gene fusion in acute myeloid leukemia patients.

When to consider testing

For AML patients identified as having an NPM1 mutation, MRD testing is recommended2 at:

  • Time of diagnosis.
  • During morphologic remission with full or partial hematologic recovery.
    • Following two cycles of chemotherapy (peripheral blood {PB}).*
    • At the end of consolidation (bone marrow {BM}).
    • After the end of consolidation, in PB or BM for 24 months. BM every 3 months or PB every 4-6 weeks.
      • *Either 2 induction cycles or 1 induction and 1 consolidation cycle; includes the time point before allogenic hematopoietic cell transplantation (allo-HCT).

Test in Focus

Mayo Clinic hematopathologist Rong He, M.D., discusses Mayo Clinic Laboratories’ innovative approach to monitoring measurable residual disease in patients with acute myeloid leukemia. The combination assay uses dual testing methodologies to identify genetic biomarkers associated with disease presence.

Beyond the test result

The Molecular Hematopathology Laboratory at Mayo Clinic offers a comprehensive suite of MRD testing, enabling full-spectrum testing under one laboratory roof. Staffed by experienced laboratory scientists who are well-versed in testing nuances, our laboratory experts provide content expertise to support testing decisions and results. 

Learn more about how to order these evaluations at your institution.


References

  1. aml.pdf (nccn.org)
  2. Heuser M, Freeman SD, Ossenkoppele GJ, et al. Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2021 Dec 30;138(26):2753-2767. doi:10.1182/blood.2021013626. PMID: 34724563; PMCID: PMC8718623.