Work-up of Myelodysplastic Syndromes

Hetty Carraway, MD: When this happens, what is the standard work-up for myelodysplastic syndrome [MDS] that you recommend for patients with MDS that may help your colleagues in the region?

Guillermo Garcia-Manero, MD: The standard first test is to do a simple CBC [complete blood count]. That is going to tell you if you have a low white blood cell count, if you have anemia—the most common feature that we see in our patients—or if you have low platelets, something that we refer to as thrombocytopenia. Seeing that will prompt a number of secondary tests. You will test to see if there’s a reason for the anemia, looking for iron deficiency, vitamin B12, and folate, for instance. Sometimes the patients will present with some inflammatory type of feature, so you might want to make sure there’s no connective tissue disorder or some type of infection.

The bottom line is that the patient will need a test we call a bone marrow examination. A bone marrow examination has two different procedures. In one, the bone marrow aspirate, we retrieve blood from inside the bone marrow cavity with a relatively thin needle. That’s where the stem cells of the bone marrow, which later create the blood, reside. The other test is a bone marrow biopsy, where we retrieve a little bit of bone from that area with a slightly thicker needle, and it allows us to look at the architecture of the bone marrow. Those two specimens allow us to look at the shape of the cells, which we call morphology. This is how we confirm the diagnosis, as do other tests such as the chromosome test and genomic analysis. Sometimes we use something called flow cytometry, which is another way to look at the shape, or paint the cells if you will, to confirm the diagnosis when we are in doubt.

This is very important because a number of years ago, we did an analysis here at The University of Texas MD Anderson Cancer Center that questioned whether we should do a bone marrow test on every patient that comes to our center. Like the Cleveland Clinic, MD Anderson is basically a referral hospital. To my surprise, we found a 15 to 20 percent discrepancy rate between the inside and outside tests. It’s not to say that the doctors outside Cleveland Clinic or MD Anderson don’t know how to perform these diagnostic procedures, but sometimes these diseases can be complex to diagnose. Sometimes the time from the original visit to the second visit makes the disease change. The bottom line is that a second look in our referral center results in changing the diagnosis and, often, the treatment in close to 20 percent of our patients. This is a key part of the assessment of our patients. When they come to see you for a second opinion, you need to confirm the diagnosis, the percentage of blasts, cytogenetics, and molecular alterations.

Hetty Carraway, MD: I completely agree. The work-up for a patient with myelodysplastic syndrome is pretty complex, and we often get patients with their first diagnosis. But when patients come for a second opinion, we review the outside bone marrow biopsy if we can get it. That can be challenging because it takes so much time. There are occasions when we just repeat the bone marrow biopsy in order to make sure our diagnosis is at the same level. We’ll talk more about this in terms of the risk level for MDS.

But all the things you highlighted really do matter in assessing the state of the myelodysplastic syndrome for that individual patient. The bone marrow aspirate is a key component to understanding a patient’s inherent risk of progression to a more aggressive type of disorder such as leukemia, or even if there are certain features to the MDS that tell us if it will be a slower-progressing MDS. For all those reasons, it helps us guide therapy and some of the ultimate decisions that we come together to make.

We also do a lot of the same blood work that you talked about with regard to working up any inflammatory disorder. We look for other entities like LGL [large granular lymphocytic] and PNH [paroxysmal nocturnal hemoglobinuria] by blood work, and even an EPO [erythropoietin] level. We’ll talk about why that’s something we check for patients specifically if they have anemia as part of their presentation, which many of our patients with MDS do.

Transcript Edited for Clarity