What Is MRD?

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CLL expert, Dr. William Wierda from MD Anderson Cancer Center in Houston, describes the meaning of MRD or minimal residual disease. Dr. Wierda explains how MRD is evaluated and how this MRD status relates to remission in CLL.

The Ask the Expert series is sponsored through an educational grant to the Patient Empowerment Network from Pharmacyclics, Inc.

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Transcript

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Jeff Folloder:

One of our CLL community members wants to know what is MRD, and how did they get there?

Dr. Wierda:

So minimal residual disease, or MRD, is a parameter that we evaluate after patients have had treatment, and it is an indicator of whether or not we can identify any disease by the very sensitive methods that we use to detect disease.  There are a few methods that you can use.  Generally speaking they're—if you're evaluating for minimal residual disease they're more sensitive than using a microscope.

So the CLL cells under the microscope look like normal lymphocytes.  We know that there are leukemia cells there under the microscope if there are too much of—too many of the lymphocytes there.  So, for example, if you look at a normal bone marrow, there should be less than 17 to 20 percent lymphocytes.  If you have an individual who has 50 percent lymphocytes in their bone marrow, that's consistent with having residual disease.  And so the complete remission criteria that we use is evaluating the bone marrow with a microscope, and individuals have to have less than 30 percent lymphocytes in the bone marrow.  And that's the standard criteria for complete remission by microscopic evaluation.

When we talk about minimal residual disease and the methods that we use to evaluate minimal residual disease, we can tell if one in 10,000 cells is a CLL cell, which is much, much, much, much, much more sensitive than using the microscope.  And so, for example, if you have an individual who has 5 percent lymphocytes in their bone marrow, which is the normal range, you would call that individual in complete remission.

But we can go with flow cytometry or a molecular method and say, okay, of those 5 percent lymphocytes are any of them CLL cells?  And in some individuals those—they may—we may be able to identify CLL cells among that small percentage of cells, and that individual would be qualified as having minimal residual disease.  If we can't detect any, then that patients would be minimal residual disease free.

So flow cytometry by four-color flow cytometry or six-color flow cytometry or even eight-color flow cytometry is one very sensitive method that we use to evaluate for minimal residual disease.  PCR for the immunoglobulin heavy chain, variable gene is another method that has been used to evaluate for minimal residual disease

Clinically, it's an important parameter to look at because we know patients who are minimal residual disease free, or MRD negative, have a longer remission than patients who are MRD positive.  And so some of the things that we're looking at now in terms of our clinical trials is can we increase the proportion or the percentage of patients that we treat into the MRD-negative category, and we think by doing that we will be able to appreciate generally longer remissions and longer survival with the treatment if we can show that the rate of MRD-negative remission is higher with the treatment.

Jeff Folloder:

So if I'm hearing you correctly, obtaining that MRD status would be the best expectation for treatment?

Dr. Wierda:

That would be the best expectation for treatment that we can demonstrate currently, yes.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on March 29, 2015