Minimal residual disease, or MRD, describes the small number of cancer cells that can remain in the body after treatment. These leftover cells are too few to be detected by traditional methods and often cause no symptoms, but they have the potential to multiply and lead to a relapse. MRD testing uses highly sensitive methods to find even one cancer cell among a million healthy cells, making it a valuable tool for managing blood cancers like leukemia, lymphoma, and multiple myeloma.
The Significance of Bone Marrow in Blood Cancers
Bone marrow is the soft, spongy tissue inside bones that functions as the body’s production center for blood cells. This is where hematopoietic stem cells mature into red blood cells, which carry oxygen; white blood cells, which fight infection; and platelets, which help blood to clot. Because of its role in blood formation, this tissue is central to the development of blood-related cancers.
Cancers like leukemia and multiple myeloma originate in the bone marrow when the normal process of blood cell development goes wrong, leading to the uncontrolled production of abnormal cells. These malignant cells accumulate in the marrow, crowding out healthy, blood-producing cells. This disruption leads to symptoms associated with these diseases, such as anemia, frequent infections, and bleeding.
Because blood cancers originate in the bone marrow, it is the primary reservoir for malignant cells. After treatment, it is the most logical place to search for any remaining disease. Even when cancer is undetectable in the bloodstream or by physical exams, a small population of cells can hide in the marrow. MRD testing is designed to find these hidden cells.
How MRD in Bone Marrow is Measured
Measuring MRD begins with a bone marrow aspiration and biopsy. This is a procedure where a needle is used to withdraw a small amount of liquid marrow and a core of solid bone from the hip bone. This sample provides the material needed for the highly sensitive laboratory analyses that follow.
In the lab, technicians employ advanced technologies to find rare cancer cells. One common method is multiparameter flow cytometry. This technique uses antibodies that bind to specific protein markers on the surface of cells. A laser-based instrument then analyzes the cells, identifying and counting any that display the unique protein signature of the cancer.
Another method is the polymerase chain reaction (PCR), which can amplify specific genetic material. This method targets unique DNA or RNA sequences found only in the cancer cells. By making millions of copies of these sequences, PCR makes them abundant enough to be detected.
A more recent technology is next-generation sequencing (NGS). NGS can analyze millions of DNA fragments at once, searching for the specific genetic mutations that characterize a patient’s cancer. This approach identifies unique genetic “barcodes” from malignant cells, providing an accurate, quantitative assessment of any residual disease.
Understanding MRD Test Results
MRD test results are reported as either negative or positive, each with different implications for a patient’s prognosis. An MRD-negative result means no cancer cells were detected in the bone marrow sample. This is considered a deep remission and is associated with a lower chance of relapse and more favorable long-term outcomes.
Achieving MRD negativity is a treatment milestone, as it suggests that the therapy has been highly effective at clearing the cancer. However, an MRD-negative result does not guarantee that a relapse will never occur. For this reason, ongoing monitoring remains part of the care plan.
An MRD-positive result indicates that a small number of cancer cells were found in the bone marrow. While not a treatment failure, this result suggests a higher risk of future relapse compared to an MRD-negative status. The specific level of MRD is also important, as detecting one cancer cell in 100,000 is different from finding one in 10,000.
How MRD Status Guides Treatment Decisions
A patient’s MRD status helps oncologists tailor treatment plans. It allows for medical decisions to be adjusted based on an individual’s specific response to therapy, moving beyond a one-size-fits-all approach.
For a patient with an MRD-positive result, the detection of residual cancer cells may prompt a change in strategy. A physician might recommend intensifying the current treatment, switching to a different therapy, or considering more aggressive options like a stem cell transplant to reduce the risk of relapse.
Conversely, if a patient maintains a consistent MRD-negative status, their doctor might determine it is safe to reduce the intensity or duration of treatment. This can lessen treatment-related side effects and improve quality of life without compromising the outcome.
MRD testing is also used for long-term surveillance after treatment is complete. A change from MRD-negative to MRD-positive can be an early warning of the cancer’s return. This molecular relapse is often detected months before clinical symptoms appear, allowing for early intervention that can potentially prevent a full clinical relapse.