Updates in Myelodysplastic Syndrome - Episode 2

Clinical Presentation and Symptoms of MDS


Mikkael Sekeres, MD, MS: Let’s take a step back for a second and talk about the World Health Organization [WHO] classification of MDS [myelodysplastic syndrome]. How did it change in 2016, and how does it inform what you talk to patients about?

Jamile M. Shammo, MD: Yeah. I think the first thing that you have to think about is the distinction between lower-risk disease and high-risk disease. When it comes to that, you have to think about the blast percentage. Anything below 5%, the question becomes how many lines of dysplasia or lineages are affected by dysplasia. Here the WHO 2016 totally eliminated the word refractory anemia because it’s been replaced by either single-lineage or multilineage dysplasia, depending on the lineages. But remember, all those patients had to have a blast percentage below 5% in order to belong to that category. The next question becomes, how many ring sideroblasts do you have on the iron stain? If it’s anything over 15%, or if it’s 5% plus SF3B1 mutation on the NGS [next-generation sequencing] panel, then you make the diagnosis of MDS RS [ring sideroblast]. Again, you classify them by single lineage versus multilineage dysplasia.

If you have a blast count over 5%, then again, you’re talking about excess blast 1, up to 9% or 2, between 10% and 19%. Finally, there’s 1 category which is MDS with del [deletion] 5q. There again, all patients have to have blast count below 5% and only either deletion of 5q plus 1 genetic abnormality, excluding chromosome 7, either del 7 or… It could be anything else except that specific mutation. Finally, for all other cases that cannot be classified in either one of those categories I just mentioned, it’s MDS unclassified.

Mikkael Sekeres, MD, MS: Wow, I’m really impressed. You did it off the top of your head. That was the entire summary of the World Health Organization’s classification. She is amazing. How do patients tend to present to you? What are the classic symptoms for somebody with MDS?

Ellen K. Ritchie, MD: It comes in a multivariate way. There are some patients that have no symptoms that are going for a hip replacement. They find that they have low blood counts, and they end up coming to me. I think fatigue is a major symptom that some patients have when they present to their primary care physician—that they’re just incredibly tired and worn out and they can’t do the things that they used to do. They are found to have cytopenias, and they’re sent to a hematologist. There are other patients that present more dramatically. There are patients who present with MIs [myocardial infarctions] because they have low hemoglobin hematocrit, which is a very dramatic presentation; bleeding of some kind; or infections that have been recurrent. I saw a patient the other day who for the last year has had UTIs [urinary tract infections], or cellulitis, or various infections, where, unbelievably, she’s gotten antibiotics from an MD with no CBC [complete blood count]. So, after her 10th infection this year, which was a tooth infection, finally someone did a CBC where she was found to be profoundly neutropenic. But these are the different ways, I think, that patients present to me: some in a very nonsymptomatic manner, all the way up to a dramatic presentation.

Rami Komrokji, MD: I agree. I think it’s important to remember that the presentation is really unspecific. It’s resultant of the cytopenias and their complications. It’s important to remember that most…MDS patients are anemic, and, unfortunately, many of them will become transfusion-dependent down the road. MDS is actually 1 of the 5 common causes of anemia in older patients, and that anemia is not an aging phenomenon. There is always a cause for the anemia. Anemia tends to be the most common…sequela of anemia. As mentioned, some patients present with the extreme of a heart attack or unstable angina. Then, obviously, if patients are thrombocytopenic or neutropenic, there are often complications.

Mikkael Sekeres, MD, MS: So, if I could summarize what I’ve just heard from everyone, the fabulous insights into people, they will either present with symptoms that are reflective of their underlying cytopenias—multiple infections; fatigue from anemia, or other things that go along with anemia—I’ve seen headaches and heart attacks also—or bleeding from thrombocytopenia. They tend to be older, so median age of 71 years. I think it’s fair to worry about MDSs in somebody who’s in his or her 70s or 80s, and myelodysplastic syndrome does increase in incidence rate with age. I guess the one thing we haven’t covered yet is what’s the distinction between MDSs and acute myeloid leukemia [AML], since you’re the expert with the World Health Organization?

Jamile M. Shammo, MD: Yes. Well, thank you. It’s interesting because I may be old school, and I believe that the new WHO classification considers AML as anything 20% or greater in terms of blasts, either in the bone marrow or in the peripheral blood. But I do think that patients who have blasts between 20% and 30%, and it’s been shown also repeatedly in various prognostic schema, that their outcome really isn’t all that different from those who have EB, or excess blasts 2. There is a subset of older patients who may have had MDS that may have blast percentage around 21% to 22%, but they don’t necessarily behave in the same fashion de novo AML might. They have more of an indolent course. But, technically speaking, for clinical trial inclusion, 20% is the cutoff that might distinguish both—and I’m curious to hear what you guys think.

Ellen K. Ritchie, MD: I agree with you that it’s really the same disease. As you go, that 26% blast patient really is going to behave just like your RAEB [refractory anemia with excess blasts]-2 patient. But, for clinical trial purposes, they definitely fit that 20% cutoff and are usually treated in our institution, in a clinical trial if possible, at that 20% cutoff. But, when I talk to patients, 20% is so arbitrary. At their prior bone marrow biopsy, they were 18%, and I repeated a bone marrow biopsy and it’s 26%. They’re suddenly terribly upset that they had AML, but I have to explain it really is the same disease. I don’t see that there’s a real distinction.

Mikkael Sekeres, MD, MS: It’s a great point, and I think I make similar points to both of you. I’m sure, Rami, with my patients that the arbitrary distinction between 17%, 18%, and 19% blasts as well as 21%, 22%, and 23% could be differences in counting by a pathologist. There are studies that have shown…that pathologists, even with blasts, don’t necessarily agree, or moving a bone marrow biopsy needle a millimeter over and getting a slightly different sample from the marrow because the marrow itself is heterogeneous.

Patients hear the word leukemia and get very scared, and I think putting that in context that MDS and leukemia with 20% to 30% blast is really part of a continuum. We started this discussion talking about next-generation sequencing and identifying some of these somatic mutations that patients can acquire over a lifetime. The distinction between lower-risk MDS, higher-risk MDS, and low-blast-count AML is the acquisition of an additional 1 or 2 abnormalities that have occurred over years.

Transcript Edited for Clarity