What is Minimal Residual Disease (MRD)?

After treatment, there may be a small number of cancer cells that remain in the body. This is referred to minimal residual disease (MRD). The remaining number of cells may be so small that they do not cause any physical signs or symptoms.

They usually go undetected through traditional methods, such as viewing cells under a microscope or by checking for abnormal serum in the blood. If a patient receives an MRD positive test result, it means that residual (remaining) cancer cells have been detected. A negative result means that no residual disease is detected.

. What role does Minimal Residual Disease (MRD) assessment play in-patient care?

Any remaining cancer cells can become active and begin to multiply, causing the patient to relapse. MRD assessment helps indicate if the treatment was not completely effective. Minimal residual disease might be present after treatment because not all the cancer cells responded to therapy.

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Is a negative MRD result a positive sign?

A positive test result for MRD, known as “MRD positivity”, indicates that residual cancer cells are present in the body after treatment. When a patient tests negative for minimal residual disease, known as “MRD negativity”, there are no remaining cancer cells.

Being “MRD negative” is an encouraging outcome for a patient with blood cancer. MRD negativity means that even with advanced, sensitive tests, no cancer cells were detected. According to studies, MRD negativity is associated with longer remissions and potentially longer rates of survival for certain blood cancers.

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How does MRD testing affect my treatment?

Testing for MRD can help our treatment team distinguish between patients who need additional or different treatment from those who do not. This knowledge can also guide treatment decisions and improve patient outcomes.

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Minimal residual disease testing helps:

● Show how well cancer has responded to treatment ● Confirm and monitor remissions ● Detect cancer recurrence sooner than other tests ● Identify a higher risk of relapse in patients ● Identify the need to restart treatment ● Identify patients who are candidates for procedures such as stem cell transplantation or combination therapy.

When would doctors test for MRD?

Testing for MRD in patients is dependent on varying factors specific to the patient’s disease.

Patients may be tested:

● After bone marrow transplantation. ● After the last cycle of a planned combination therapy. ● During treatment. ● After one year of maintenance therapy. ● To confirm the depth of remission. ● At regular intervals, once treatment is completed. ● At other specific times. .

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What are the techniques used to detect MRD?

MRD testing uses highly sensitive methods such as , polymerase chain reaction (PCR), and next-generation sequencing (NGS). Each of these tests uses bone marrow cell samples taken through aspiration, or peripheral blood cells taken through a vein.

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MRD Testing in Specific Blood Cancers

The type of MRD testing used depends on the type of blood cancer.

Acute Lymphoblastic Leukaemia (ALL) For patients with ALL, MRD is detected through flow cytometry, PCR, and NGS.

● When treating paediatric and adult ALL, MRD is part of routine testing. ● MRD can predict the effectiveness of a specific treatment after the induction phase of ALL treatment. ● MRD can identify patients who are at higher risk of relapse. This allows administration of earlier or alternative therapies. MRD can determine patients who may benefit from a bone marrow transplantation. .

Chronic Lymphocytic Leukaemia (CLL) For patients with CLL, MRD is detected by flow cytometry and PCR.

● MRD negativity in patients after CLL therapy may have better treatment outcomes. ● MRD positivity in patients after treatment are potential candidates for treatment intensification, consolidation and maintenance strategies. .

Chronic Myeloid Leukaemia (CML) For patients with CML, MRD is detected through PCR.

● PCR can detect the Philadelphia (Ph) chromosome found in 95% of CML patients. ● PCR can detect one Ph+ CML cell in one million healthy cells. ● MRD monitoring helps predict resistance to treatment and guide the course of the patient’s treatment. .

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Lymphoma For patients with , MRD is detected through flow cytometry and PCR.

● MRD testing can detect patients who are at risk of relapsing, allowing them to receive additional treatment. ● MRD testing is used in follicular, mantle cell and diffuse large B-cell lymphoma (DLBCL). ● Patients treated for and achieve MRD negativity have shown to have prolonged remissions. ● Studies have demonstrated that DLBCL patients who achieved remission and MRD negativity after treatment were more likely to remain in remission compared to patients who had achieved remission with MRD positivity.

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Myeloma For patients with myeloma, MRD testing uses flow cytometry, NGS, and imaging tests.

● PET-CT scans combined with other tests help doctors find disease present outside the bone marrow. ● Patients who achieve MRD negativity after treatment live longer without disease progression, according to several studies.

Disclaimer: The information on the Centre For Clinical Haematology website is intended for educational use. It should not be considered or used as a substitute for medical advice, diagnosis or treatment from a qualified health professional.

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