MDS: Typical Patient Presentation, Diagnostic Process, and Evolving Terminology


Moderator Rami Komrokji, MD, introduces the panel and invites expert pathologist Sanam Loghavi, MD to lead a discussion on the typical patient presentation and diagnostic process in MDS, which was recently renamed as ‘myelodysplastic neoplasms’ in the 2022 5th edition of the World Health Organization (WHO) classification of the disease state.


Rami Komrokji, MD: Hello and welcome to this OncLive® Peer Exchange titled, “Key Advances in Diagnosis, Treatment, and Management of Myelodysplastic Syndromes.” I’m Rami Komrokji, a hematologist and vice chair of the Malignant Hematology Department and the head of the leukemia and MDS section at Moffitt Cancer Center in Tampa, Florid]. I’m joined today by a panel of experts in the field of MDS [myelodysplastic syndromes]. I would like to welcome my esteemed fellow panelists to introduce themselves. Dr Cluzeau?

Thomas Cluzeau, MD, PhD: Hello. My name is Thomas Cluzeau, from Nice University Hospital in Nice, France. I am a member of the group of oncologists for myelodysplasia.

Guillermo Garcia-Manero, MD: Hi. My name is Guillermo Garcia-Manero. I’m from the University of Texas MD Anderson Cancer Center in Houston, Texas.

Sanam Loghavi, MD: Hello. I’m Sanam Loghavi. I’m a hematopathologist and a molecular pathologist at MD Anderson Cancer Center in Houston, Texas.

Uwe Platzbecker, MD: Hello. My name is Uwe Platzbecker, from the University Hospital Leipzig in Leipzig, Germany.

Rami Komrokji, MD: Welcome, everyone, and thank you for joining me. Today, we are going to discuss a number of updates in MDS that were presented at recent meetings, including the American Society of Hematology [ASH] 2022 meeting. We will discuss the data in the context of other recent updates to the treatment landscape and their impact on clinical practice. Let’s get started. We will cover the disease background, talk about diagnosis, risk stratification. Sanam, I’m going to ask you to set the stage for us. You are the best to tell us about how to diagnose and classify this disease, and how patients present. So, please.

Sanam Loghavi, MD: Sure, happy to. Myelodysplastic syndromes, essentially, are bone marrow failure syndromes. The patients typically present with sequelae of cytopenias. So anemia, it can be shortness of breath, tiredness, infections if they have leukopenia or neutropenia, and then thrombocytopenia can present with bleeding. But for diagnosis, the gold standard of getting a diagnosis of myelodysplastic syndrome is doing a bone marrow biopsy. On a bone marrow biopsy, nowadays, adequate diagnosis and prognostication of MDS require molecular testing, cytogenetic testing, which includes a conventional karyotype, and FISH [fluorescence in situ hybridization]. You don’t necessarily have to do it all, but it can be a constellation of these. For molecular testing, most academic and private practice settings now have panel-based NGS [next-generation sequencing] testing that covers genes that are recurrently mutated in myeloid malignancies. Then, obviously, morphology remains the gold standard for making a diagnosis of myelodysplastic syndrome.

Rami Komrokji, MD: One thing to bring up is what are the things that could mimic MDS, especially in the hematopathology, when you review those cases. Are there things to highlight for the audience to keep in mind? What’s the differential diagnosis in those cases?

Sanam Loghavi, MD: Of course. I would say it depends on the setting you’re practicing in. For a practice like mine, most patients who present to my practice do have MDS. But it’s more likely that patients who present with cytopenias do not have MDS, and they have other causes for their cytopenias. This could include nutritional deficiencies, like vitamin B12 deficiency, folate deficiency. Copper deficiency can give you morphologic dysplasia, often with neutropenia and anemia. Then there are other, more common, non-neoplastic conditions, like other diseases, infections can cause cytopenias, HIV can cause cytopenias. You can see morphologic changes in the bone marrow that are associated with HIV. So, there is a list of things you have to rule out and exclude before you go to a bone marrow biopsy that are more common. But once you get to an unexplained reason for the patient’s cytopenias, you have to start thinking about MDS and do a biopsy.

Rami Komrokji, MD: Guillermo, is it standard now that we get NGS testing on all the patients?

Guillermo Garcia-Manero, MD: This is a very interesting conversation. We’re at the annual ASH meeting, and there is a lot of discussion about this. I think, in the United States, and in European countries, it should be the standard. But the reality is that may not be something we have in every country, in every continent. It’s an interesting question because we are moving into these very sophisticated molecular prognostic classifications, such as the IPSS-M [International Prognostic Scoring System-Molecular]. But the question is, what’s going to happen? Are we going to have 2 systems to look at this? Obviously, if you have access to this kind of technology, I don’t see why you would not use it. But does everybody have it? No. We’re going to have to figure out how we move forward. So, the short answer is, yes, you need the molecular panel.

Rami Komrokji, MD: I always emphasize to even our fellows that the most important step is establishing the diagnosis. And many times, it sounds like a straightforward thing. But it’s dependent on a good hematopathologist who reviews the slides. I think there is a difference in the pattern between Europe, where you still read your aspirates, your hematologists are better than us, vs us, who are dependent completely on hematopathology. But it’s crucial. During our practice, we’ve discussed cases all the time, patients who were thought to have MDS received treatment with hypomethylating agents for a year, and they had iron deficiency or copper deficiency. As simple as it looks, getting all the testing and establishing the diagnosis is probably the most important first step.

Uwe Platzbecker, MD: Can I challenge Sanam again and ask her a question? Shouldn’t we call MDS now myelodysplastic neoplasm, according to the recent update from the WHO [World Health Organization]? Would you agree?

Sanam Loghavi, MD: I agree. For some background, the fifth edition of the WHO classification of the disease state has renamed myelodysplastic syndromes as myelodysplastic neoplasms, with the intention of emphasizing the neoplastic nature of the disease, and that this is a malignancy. I think they’re keeping the abbreviation the same for the sake of consistency, and not to confuse it with MPNs [myeloproliferative neoplasms]. But yes, if you want to be up to date, the correct terminology is myelodysplastic neoplasms.

Uwe Platzbecker, MD: We use it in our clinic now as a common term, and you just mentioned that MDS, the acronym, stays the same, which makes it easy. But I think also for reasons of consistency with MPN, where you may say it is ET [essential thrombocythemia] and neoplasm, I think it is, on a molecular basis, but more indolent than many MDS cases. So at least we have adopted it in our clinic. Just for the sake of completeness, I wanted to ask you that.

Guillermo Garcia-Manero, MD: Of course, we’re going to follow the terminology that is accepted. And I am a supporter of the last edition of the WHO more than the ICC [International Consensus Classification]. I disagree with a lot of the concepts in the ICC. But when it comes to the acronym, I’m not sure. Because there was a discovery in the last few years that was important to me, this crosstalk between comorbidities, mutations, and myelodysplastic syndrome. The question is, by changing the name, we’re negating the syndromic aspect of this disease. In other words, we all accept that maybe there could be a connection between cardiovascular disease, mutation, and MDS. And by focusing on MPN, we may somehow be missing that point. And it’s just for.

Uwe Platzbecker, MD: That’s a topic for the next WHO edition.

Rami Komrokji, MD: It’s an important point.The background, even in the United States, is that, for many years, insurance would not recognize that MDS is a type of cancer and they would not cover it.

Sanam Loghavi, MD: That was one of the reasons behind that, yes.

Rami Komrokji, MD: I think the name is a bit like, MDS, we are so used to it, so it’s difficult to change. But also, to Guillermo’s point, I think we still have to think of MDS as a spectrum. That point is very well taken.

Transcript edited for clarity.

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