ESH AL 2018 | How has MRD changed our ability to diagnose leukemia?
Measurable residual disease (MRD) testing is revolutionizing our ability to determine the disease state of a patient. In this video, Elizabeth Macintyre, MD, PhD, of the Hôpital Necker-Enfants Malades, Paris, France, speaks about the benefits of MRD and compares it to some alternative methods of screening. This interview took place at the 2018 European School of Hematology (ESH) Clinical Updates on Acute Leukemias.
Transcript (edited for clarity)
Succinctly, what I teach to the students is at diagnosis, there’s about a kilogram of tumor. Now in a leukemia it’s disseminated, but what we call morphological complete remission, it’s just less than five percent blasts in a regenerating bone marrow. so if you say five percent is a two log reduction from a hundred percent, you don’t know whether you’ve got ten to the ten million cells a kilo, corresponding to about ten to the twelfth cancer cells, or whether you’ve got none...
Succinctly, what I teach to the students is at diagnosis, there’s about a kilogram of tumor. Now in a leukemia it’s disseminated, but what we call morphological complete remission, it’s just less than five percent blasts in a regenerating bone marrow. so if you say five percent is a two log reduction from a hundred percent, you don’t know whether you’ve got ten to the ten million cells a kilo, corresponding to about ten to the twelfth cancer cells, or whether you’ve got none.
So historically, the game in MRD was to be as sensitive as possible and to continually monitor patients. But with time, because MRD became fashionable about twenty to thirty years ago, with time it’s much more, we need to provide relevant information at the time when therapeutic decisions are made so you know, schematically or in a somewhat sensationalist context there’s not that much point in spoiling the last three months of a patient’s complete remission by announcing that they’re going to relapse if you don’t have something constructive to suggest.
So that very much depends on the kinetics of relapse; if you’ve got rapid kinetics, you’d have to do MRD follow-up every two weeks and nobody wants a bone marrow every two weeks, whereas in non acute leukemia disorders, you can have kinetics of relapse that can be measured over months or even years.
So there there’s a whole concept for pre-emptive therapy. But to come back to your initial question, of course it’s got to be measurable and and certainly my point of, my standpoint is I’d prefer something that’s slightly less sensitive but robust than something that’s very sensitive but not reproducible. And the final thing I would say is for DNA diagnostics you can’t have something that’s more sensitive than the detection of one copy, and in a hundred nano grams of DNA you’ve got 15,000 cells. So if you’re only going to analyze 100 nanograms of DNA you can’t promise to detect one cancer cell in a million, one in a million unless you’re working at the RNA level because you because the cells transcribe at different rates, and that’s one of the reasons we like DNA diagnostics because it’s easier to equate response between patients
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