Myelodysplastic Syndrome Diagnosis and Risk Assessment


Gail Roboz, MD; Azra Raza, MD; and Amy DeZern, MD, MHS, discuss the clinical considerations and risk assessments inherent to a diagnosis of myelodysplastic syndrome.

Gail Roboz, MD: Hi everyone, and welcome to this OncLive® Peer Exchange panel discussion, “Updates in Treatment for Myelodysplastic Syndrome.” My name is Gail Roboz. I am lucky today to be joined by a group of colleagues and friends, all experts in the treatment of myeloid malignancies. I will be joined today by Drs Amy DeZern, James Foran, Rami Komrokji and Azra Raza, and welcome to all of you. Today we are going to focus on MDS, myelodysplastic syndrome, which is a heterogeneous disease that necessitates an individualized treatment approach and careful monitoring, to slow disease progression and prevent complications. We will discuss some of the challenges in managing MDS, and there are many, as well as accurate risk stratification, complications associated with transfusion dependence, and practical considerations for treatment, including some discussion of emerging therapies. Thank you very much for joining the panel and the discussion. We are going to launch right into it. The first section is going to be to discuss MDS diagnosis and risk assessment. What I am going to do, this is really a conversation, I will toss things out to my colleagues, and we are going to try to engage in some discussion and opinions and guidelines for all of you about all the different areas of MDS to discuss. Azra, I will toss to you first, when you are initially thinking about working up a patient for MDS, what are the triggers? How do the patients get to you? And what are the initial portions of the work-up to kick off making the diagnosis?

Azra Raza, MD: Thank you, Gail. I am delighted to be on this panel with everybody. To begin with, I think we all share one thing in common, which is that we seem to be at tertiary care centers for MDS. So that by the time patients come to us, some of our community colleagues who are extremely knowledgeable and well informed have already ruled out things like copper deficiency or some nutritional reason for the patient to have a cytopenia. And a lot of the diagnostic work-up has pretty much been done. Patients generally would come to me with a cytopenia, and 80% of the time it is anemia. Of course, being obsessed with the disease, my first thought is always MDS, but it is important not to be guided just by that. You need to think in an overall way about the patient’s lifestyle, age, risk factors for MDS, all kinds of things before launching into a million-dollar work-up. I’ll let you ask somebody else, or if you want me to continue, I’m happy to tell you that besides a CBC [complete blood count], how we proceed.

Gail Roboz, MD: I think you touched on one thing just in launching into that, about risk factors, and I am going to split this, I’ll ask you to start, and then I’m going to kick it to Amy about family history, which is something we don’t think about that much in MDS. But how do you think about risk factors when you have that patient coming in with cytopenias? And right before your million-dollar work-up, what are the risk factors you consider?

Azra Raza, MD: I think the biggest risk factor and biggest carcinogen for MDS is age. If it’s a 40-year-old with leukopenia, I’m going to think very differently than if it’s a 72-year- old person. Sometimes even the gender matters because the disease is more common in men, whether it’s twice as common or a third of the patients have more of it. Other risk factors are exposures. What is the main occupation of this person? What did they do for the last 50, 60 years? Living in New York, Gail, I do not know how many people you see, but we regularly see people who have 9/11 terror attacks kind of exposure, for example. We do not see that many patients anymore with Agent Orange. But recently, I had a patient who insisted that he had a lot of benzene exposure, and when I kept trying to tell him that benzene was removed from the list of chemicals a long time ago, he brought a lot of data to show me how much diesel fuel, for example, can contain benzene, things like that. I think age, exposure, family history, all those things come into play.

Gail Roboz, MD: You brought up a couple of points to highlight for the audience that World Trade Center exposure—and causality, is going to be very difficult to establish always—but it is a covered expense. I think that for patients with exposure and who were down there, we have increasingly utilized the World Trade Center coverage options to help our patients in terms of financial support for some of the medications. That is one point. The second one I just cannot resist, because you threw out the work-up for copper. I did have the craziest case of somebody who was using a very strange, very natural toothpaste that chelated all the copper, and for all the world, she was sent to me for MDS for a transplant, and ended up needing a switch in toothpaste. There are some crazy things that can creep into the diagnosis. I think your point is so important to stay broad, think about lots of different options. On the benzene front, I think we all have somebody who worked at a gas station for the summer when they were 12 years old, and that is probably not it. But somebody who worked at a dry cleaner, and we had a pair of patients who worked for 50 years in the same dry cleaner, I think we would wonder about that. Amy, I am going to let you talk about family, because we don’t always do a great job with family history. I think there are many emerging data suggesting we need to do a much better job on family history, so help us out.

Amy DeZern, MD, MHS: I do think it is important, and I tell the fellows, gone are the days where we put “family history: noncontributory.” We probably never should have put that, but I do spend some time delving into first- and second-degree relatives. But candidly, we are talking about inherited predisposition or germline-style mutations. And it is still possible for a patient to have one of those disorders, because there can be as many as half of cases that are de novo of germline mutations, and they are not necessarily inherited. But since we are talking about how to treat these patients, anticipation and partial penetrance can confound the family history. The other thing that I think Azra mentioned very nicely is, we are quite diligent in patients who present with MDS at the age of, heaven forbid, 30, or 40, or even 50. But not only younger patients can have germline mutations. The age of onset is, we are learning, quite variable. There are certain mutated genes like DDX41, pops to mind straight away, that can certainly contribute to myeloid disease after midlife. Something that I learned in medical school was that you examine them thoroughly and look for some sort of clinical features. But the reality is patients do not always have recognizable syndromic features, and hypomorphic mutations still create a risk for malignancy without anything on an examination. Then I always ask about an antecedent history when they were young. Heaven forbid they had transfusions in their teens, but normal blood counts in the past can also mask some of those germline mutations. I think we will get into it as we talk more about variant allele frequencies and other things that make us delve even deeper as we work through a diagnosis with a patient about considering those germline predispositions.

Transcript edited for clarity.

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