Minimal Residual Disease (MRD) positive refers to the detection of a very small number of cancer cells remaining in the body even after a patient has undergone treatment for cancer. These cells are often present at levels too low to be found by standard imaging techniques or routine blood tests. MRD positive results indicate that highly sensitive tests have identified these lingering cancer cells.
Understanding Minimal Residual Disease
Even a small number of remaining cancer cells, known as minimal residual disease, can significantly impact a patient’s prognosis. These cells, though few, possess the potential to multiply and lead to a cancer relapse. Traditional methods, such as microscopic examination of bone marrow or tracking serum proteins, often miss these minute quantities of cells.
The goal of cancer treatment often involves achieving “complete remission,” where there is no visible evidence of cancer through conventional diagnostic tools. MRD testing provides a more sensitive measurement, going beyond these standard assessments to detect disease at a molecular level. For instance, in acute lymphoblastic leukemia (ALL), 30% to 40% of adult patients may relapse despite achieving complete remission by traditional methods, testing positive for MRD.
How MRD is Detected
Detecting minimal residual disease requires highly sensitive laboratory techniques capable of identifying a single cancer cell among millions of healthy cells. Common methods include multiparameter flow cytometry (MFC), polymerase chain reaction (PCR), and next-generation sequencing (NGS). These tests typically use samples from bone marrow, though some can also analyze peripheral blood.
Multiparameter flow cytometry works by identifying cancer cells based on specific proteins, or antigens, on their surface that differ from healthy cells. Cells from a sample are stained with fluorescent antibodies that bind to these distinct markers, then passed through a laser that counts the marked cancer cells. This method can detect approximately one cancer cell in 10,000 to 100,000 healthy cells.
Polymerase chain reaction (PCR) techniques, such as real-time quantitative PCR, amplify and detect specific genetic sequences unique to the cancer cells. This method is particularly useful for cancers with known genetic abnormalities, like the BCR-ABL1 fusion gene in certain leukemias. PCR can achieve a sensitivity of one cancer cell in 100,000 to 1,000,000 healthy cells by amplifying tumor-specific DNA or RNA.
Next-generation sequencing (NGS) offers an even higher level of sensitivity, potentially detecting one cancer cell in up to one million healthy cells or more. NGS identifies unique tumor-specific genetic targets by analyzing DNA or RNA sequences.
What Being MRD Positive Means
An MRD positive result indicates a higher risk of cancer relapse compared to being MRD negative. While it does not necessarily mean an immediate relapse, it provides important prognostic information that guides future treatment decisions. For example, in childhood acute lymphoblastic leukemia, MRD positivity at various points during treatment is a strong predictor of relapse and is associated with a less favorable outcome.
The significance of an MRD positive result can vary depending on the type of cancer and the specific stage of treatment. For instance, in multiple myeloma, patients who lose MRD negativity have an elevated risk of clinical relapse. Similarly, in follicular lymphoma, MRD positivity after induction therapy and during maintenance therapy is associated with inferior progression-free survival. This information helps healthcare teams assess individual patient risk and tailor surveillance strategies accordingly.
Addressing MRD Positive Status
When a patient tests MRD positive, medical professionals often consider adjustments to the treatment plan to reduce the risk of relapse. These adjustments might involve intensifying the current therapy, exploring alternative treatments, or considering enrollment in clinical trials. For example, in acute myeloid leukemia, patients with intermediate-risk disease who are MRD positive may be considered for allogeneic hematopoietic stem cell transplantation, while those who are MRD negative might continue with consolidation chemotherapy.
Ongoing monitoring of MRD status is also a common approach, allowing healthcare teams to track disease evolution and intervene promptly if the disease progresses. This approach emphasizes collaborative decision-making between the patient and their healthcare team. The goal is to identify and address the residual cancer cells before they lead to a more overt clinical relapse.