Minimal Residual Disease Testing

Medical Experts

Contributor

Karner

Kristin Hunt Karner, MD

Associate Professor of Pathology (Clinical), University of Utah

Medical Director, Hematopathology and Molecular Oncology, ARUP Laboratories

Contributor

Ng

David P. Ng, MD, FCAP, BSEE

Assistant Professor of Pathology (Clinical), University of Utah

Medical Director, Hematopathology, ARUP Laboratories

Minimal residual disease (MRD, also called measurable residual disease) is the term for very small numbers of cancer cells that a patient retains after treatment. MRD is a major predictor of relapse in many hematologic malignancies (leukemias and lymphomas) and has important implications for prognosis and treatment decision-making. Recent increases in test sensitivity enable the detection of very small numbers of cancer cells, and thus detection of MRD, in hematologic malignancies. Laboratory techniques used in MRD assessment include polymerase chain reaction (PCR), deep sequencing (a type of next generation sequencing, or NGS), and flow cytometry.

Quick Answers for Clinicians

For which malignancies is minimal residual disease assessment recommended?

The National Comprehensive Cancer Network (NCCN) and European Society for Molecular Oncology (ESMO) recommend minimal residual disease (MRD) assessment for specific hematologic malignancies, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL, including pediatric ALL), chronic myeloid leukemia (CML), and multiple myeloma.^,^,^,^,^,^,^, MRD may also be assessed in some circumstances (such as in the context of clinical trials) in other hematologic malignancies (eg, chronic lymphocytic leukemia [CLL], hairy cell leukemia, some myeloid/lymphoid neoplasms with eosinophilia, follicular lymphoma, and mantle cell lymphoma).^,^,^,^,^,

What is the role of minimal residual disease testing in nonhematologic malignancies?

The role of minimal residual disease (MRD) assessment in patients with solid tumors (eg, melanoma, lung cancer, and breast cancer) is currently being researched. There are currently no recommendations for the use of MRD testing in nonhematologic malignancies.

Which factors should be considered when choosing a test for minimal residual disease?

Assays specifically designed for minimal residual disease (MRD) testing are recommended. For flow cytometry tests, a sufficient number of colors should be used, and the validated limit of detection (LOD) should be reported. For example, in multiple myeloma, an LOD of 0.001% is required. An eight-color, two-tube flow cytometry test or a 10-color, one-tube test can meet this requirement and provide high consistency, reliability, and sensitivity. The use of flow cytometry and/or polymerase chain reaction (PCR) testing in MRD assessment is established for many hematologic malignancies; however, the role of next generation sequencing (NGS)-based tests is not as established and continues to evolve. Regardless of the test selected, a high-quality specimen should be provided for testing (eg, a first or early pull of bone marrow), and the test should be thoroughly validated.

Indications for Testing

MRD testing may be used in hematologic malignancies to:

Assess treatment response and inform treatment decisions
Determine prognosis
Monitor remission and detect recurrence

Laboratory Testing

Testing Methods

A variety of methods are used to detect MRD. The most frequently used methods are deep sequencing (a type of NGS), flow cytometry, and PCR. The choice of which technique to use depends on the phenotype and molecular signature of the disease; for example, PCR may only work for a subset of cases with specific molecular findings.

Regardless of the technique used, high sensitivity (ie, low limit of detection [LOD] or limit of quantification [LOQ]) is required to ensure detection of very small numbers of leukemic cells. The requisite LOD/LOQ is generally 0.01% of nucleated cells or less, depending on the disease.

Other testing methods, such as fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), have been used for MRD assessment in specific hematologic malignancies.^,