Myelodysplastic Syndromes: Translating Genetics to Clinical Practice - Episode 2

WHO Criteria and Diagnosis in MDS

May 12, 2016

Transcript:Mikkael A. Sekeres, MD, MS: I wonder if I could ask a follow-up question about the biology of MDS. How do you think the World Health Organization (WHO) classification reflects that biology and how do you think changes in the WHO—and we are on the cusp of a brand new WHO for myeloid neoplasms—is going to change how we reflect on the biology of the disease?

Jamile Shammo, MD: I think it remains to be seen how the final version of the new WHO classification is going to be, but it would seem that it’s going to be looking at unilineage dysplasia versus multilineage dysplasia versus MDS with RAEB-1 or RAEB-2, as opposed to your standard refractory anemia with excess blasts, which doesn’t have to be utilized anymore. So, I think it may be a cleaner version of what we already have and probably will make those patients fall into specific buckets that will make it easier to study prospectively relative to mutation analyses, cytogenetic impact, and treatment outcomes.

Rami S. Komrokji, MD: I think relevant to your question about integrating the biology in the WHO classification, currently, there is not much. Obviously, they recognize the deletion 5q as an entity because it has some therapeutic implication. I think, in 2008, there was some change saying that if patients have cytopenias with no other explanation, and certain cytogenetic abnormalities, they can be called presumptive MDS. So, that’s reflecting part of the biology. I think there had been so many discussions in many of the panels, which you are involved in, as well, about integrating the next-generation sequencing, the somatic mutations into the WHO criteria. One thing proposed is the refractory anemia with ring sideroblasts. Maybe if they have more than 5% ring sideroblasts and an SF3B1 mutation, that will be called refractory anemia with ring sideroblasts. I think this is going to be a changing field. Acquired somatic mutations are not yet integrated into the presumptive diagnostic criteria for MDS, and I don’t think they will be in the next WHO revision.

Mikkael A. Sekeres, MD, MS: I wonder if we could shift gears a little bit. Ellen, how do you diagnose MDS, and what are the challenges in diagnosing MDS?

Ellen K. Ritchie, MD: I feel that you need to do bone marrow biopsy in order to diagnose MDS, and for a lot of patients, that’s a huge hurdle. Their primary care doctor has referred them to me because they have a little anemia or they have a little thrombocytopenia. And when looking at this scenario, I feel it’s necessary to do a bone marrow—but there’s no other way to make this diagnosis. So, bone marrow biopsy with aspirate and a good core is important to making a good diagnosis of this disease. We also send off aspirate for cytogenetics, and we send off aspirate experimentally for next-generation sequencing, which will help add to the picture of what we think is happening in that particular patient.

I think now is a very challenging time, in some ways, to make a diagnosis of MDS because sometimes we do a bone marrow biopsy where it’s not clearly MDS, but the next-generation sequencing comes back with a couple of mutations or you find an isolated cytogenetic abnormality, which may or may not be important. So, the patient wants to know, “Do I have myelodysplastic syndrome?”, and it’s a much more complicated picture than it has been in the past. If a patient has overwhelming dysplasia, and you have cytogenetic abnormalities, and abnormalities in next-generation sequencing, it’s actually an easier discussion to have because it’s very, very clear what the diagnosis is for the patient.

I think it’s also very hard on patients when we don’t have a real diagnostic bone marrow biopsy the first time. Sometimes we have to go back and do it 3 months later or 4 months later, and explaining that it may not be that we get a good specimen and good diagnosis the first time is also a challenging thing, I think, for the physician to discuss with the patient.

Transcript Edited for Clarity