What is measurable residual disease (MRD), and why does it matter in AML care? Hematologist-oncologist Dr. Anand Patel explains how this advanced testing can detect tiny amounts of leukemia that may remain after treatment, discusses how MRD testing helps doctors assess remission, and describes the influence of MRD on ongoing AML care and treatment decisions.
Dr. Anand A. Patel is the Medical Director of the Inpatient Leukemia Service at the University of Chicago Medical Center. Learn more about Dr. Patel.
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Transcript
Katherine Banwell:
We know that testing goes beyond diagnosis. Can you explain measurable residual disease, or MRD?
Dr. Anand Patel:
Yeah. So, MRD is an incredibly important tool. The best analogy I like to use for measurable residual disease, or MRD, is an iceberg. You only know how deep the iceberg goes underneath water if you’re going down deep enough to look, and MRD is kind of that.
So, when we think about leukemia, if you look under a microscope, a really, really good hematopathologist can pick up maybe one in 100 leukemia cells. You, then, can add additional tests to kind of interrogate whether disease is there or not more deeply.
For example, patients who have these FISH abnormalities in their chromosomes that we can detect with FISH testing, you may be able to pick up one in 400 to one in 600 abnormalities when you incorporate what’s called flow cytometry.
So, looking at the markers, the abnormal markers seen on leukemia cells, that can then pick up anywhere from, say, one in 2,000 to one in 10,000.
And then, you have what are called molecular MRD markers. So, there are some molecular abnormalities. Two good examples are NPM1 and FLT3, where, depending on the testing done, you can even pick up one in 100,000 leukemia cells. So, we’ve kind of gone beyond just looking under the microscope and saying the disease is not there, at least under the microscope.
We also will complement that with whatever MRD test is most appropriate for the patient, based on their disease characteristics at diagnosis.
Katherine Banwell:
Well, and that’s really my next question, is, how does MRD influence the next steps?
Dr. Anand Patel:
So, we know that any detectable leukemia is something we don’t want to see. And patients, for example, that are in a favorable risk disease bucket at diagnosis, if after they receive up to two cycles of chemotherapy, intensive chemotherapy, for example, we’re seeing that their disease is still present at a very low level.
That may change our decision-making around the right the route to cure. We may start thinking, “Well, we know that this was a favorable risk leukemia when we kind of learned everything about it at diagnosis. But now, based on the fact that there is MRD that is not going away, we may need to think about something like stem cell transplant to try and cure this disease definitively.
Other ways this decision-making can be influenced is, do we need to intensify the therapy that we are giving to try and eradicate or get rid of that MRD? MRD not only influences decision-making about transplant or not; it can also influence decision-making about what might need to be done in someone who ultimately receives a stem cell transplant to keep the disease in a remission, what we call maintenance therapy. And the concept of maintenance therapy can also be applied in patients who don’t ultimately go into a transplant.
So, we’re not going to keep giving you the same sort of chemotherapy you’ve received up until this point. But we know that we have to administer some sort of treatment, whether it’s an oral pill or otherwise, to keep the disease in a remission. Because if we do nothing, this very, very low amount of disease may become significant disease again.