Diagnosis of Myelodysplastic Syndrome



Mikkael Sekeres, MD, MS: The myelodysplastic syndromes [MDSs] are a heterogeneous collection of diseases that necessitate an individualized treatment approach and careful monitoring in an effort to slow disease progression and prevent complications.

In this OncLive® Peer Exchange, a panel of experts in oncology and hematology will discuss some of the challenges in managing the disease—including accurate risk stratification, complications associated with transfusion dependence, and practical considerations in the use of disease-modifying therapies and stem-cell transplantation. We’ll also discuss some of the data released at the 2019 ASH [American Society of Hematology] Annual Meeting.

I am Mikkael Sekeres, director of the leukemia program and professor of medicine at Cleveland Clinic in Cleveland, Ohio.

Joining me today are Dr Rami Komrokji, senior member, section head of leukemia and MDS and vice chair of the malignant hematology department at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida;

Dr Ellen Ritchie, associate professor of medicine and assistant director of the leukemia program at Weill Cornell Medicine in New York;

And Dr Jamile Shammo, a medical professor at Rush University Medical Center in Chicago, Illinois.

Thank you for joining us. Let’s get started. I wanted to start by talking a little bit about how we diagnose MDS. What is it? When you have a patient who comes to you with a referral for MDS and that diagnosis hasn’t been established, but let’s say it’s an older person who has multiple cytopenias, what’s your first step in evaluating that person?

Jamile M. Shammo, MD: I like to make sure that we rule out some of the more common conditions that might be resulting in cytopenias. I think everybody deserves to get tested for the usual: vitamin B12, folate, and for certain patients who may have bypass surgeries, perhaps think about copper deficiency. I guess if you don’t have any other explanation for the cytopenias, then I think everybody should get a bone marrow biopsy with cytogenetics. Whether or not you get an NGS [next-generation sequencing] depends on where you are. I typically get an NGS with every patient who has a potential diagnosis of MDS. Then, I think, we go by the WHO [World Health Organization] classification, which has somewhat simplified the approach to making the diagnosis of MDS by incorporating cytopenias, morphologic changes—molecular and cytogenetic.

Mikkael Sekeres, MD, MS: For NGS, how available is that to everybody? Is everybody able to send that?

Ellen K. Ritchie, MD: I think that it’s available to me very easily—both in our institution and we can send it out. The complication is paying for the NGS panel. When I send an NGS panel, I always worry about whether or not insurance is going to cover that panel for that particular patient. It governs actually where you can send that particular panel because, while I have my favorite places to send NGS panels where I feel very secure in what the results are, sometimes I have to send it somewhere where I’m actually not familiar with that organization, and that’s insurance driven. I think there are challenges to sending the NGS panel, mainly because you’re concerned about coverage. But I think it’s very helpful, when you get these results back, to help stratify your patients as to what their risk is of having a more serious disease.

Mikkael Sekeres, MD, MS: We have representatives from Illinois, Ohio, New York, and Florida, and I believe it’s state by state whether or not NGS panels for myeloid malignancies are covered. What about you, Rami? What about in Florida—how well are they actually covered?

Rami Komrokji, MD: I think they’re well covered, and I think it’s becoming more standard-of-care to get them. I think the utilization varies a little bit by the community practices in oncology. They are available now even for community oncologists. I would say, in our practice, still more than half of the patients, when we see them referred for a second opinion, have not had an NGS test done. It’s becoming more used but still a lot of the patients are not getting those at the time of diagnosis, which I think is important. It’s important to emphasize that they are not part of the diagnostic criteria. Having a mutation is not…diagnostic. But it definitely helps you make the diagnosis in the right setting.

The challenge—obviously we know about that patients with idiopathic cytopenias of unknown significance could have mutations. Patients could have what we call CHIP [clonal hematopoiesis of indeterminate potential], which is clonal hematopoiesis by aging. Mutations are not diagnostic, but there is no doubt that they help in the right settings. If you find an SF3B1 mutation with ring sideroblasts, I think that’s going to help you. In monocytosis we see a concomitant TET2, SRSF2 mutation. That’s going to help you with the diagnosis, but it’s important that the WHO does not include them as diagnostic criteria.

Jamile M. Shammo, MD: I’m very happy that you say that, because often I’ve seen community physicians making a diagnosis of potential MDS just because the NGS panel shows an abnormality, and yet you don’t have morphologic abnormality consistent with dysplasia. I think it’s important to put that together to make an accurate diagnosis.

Mikkael Sekeres, MD, MS: That’s a really great point. There are abnormalities in NGS that can be revealed that people acquire as they age, what Rami referred to as CHIP, the DNMT3A abnormalities. ASXL1 and TET2 are probably the biggest culprits that we’ve been made aware of. They’re also common in MDS.

Transcript Edited for Clarity

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