Diagnosis and Risk Stratification of Myelofibrosis


Srdan Verstovsek, MD, PhD, provides an overview of how myelofibrosis is diagnosed and what criteria are used for risk stratification.

John Mascarenhas, MD: Welcome to this CancerNetwork® presentation titled “Expert Insights Into the Treatment of Myelofibrosis.” I’m your host, Dr John Mascarenhas. I’m the director of the adult leukemia program and leader of clinical investigation within the Myeloproliferative Disorders Program at Mount Sinai in New York, New York. Joining me are Aaron Gerds, Raajit Rampal, and Srdan Verstovsek. I’d like each of them to introduce themselves, starting with Aaron.

Aaron Gerds, MD: Hi. Thank you so much, John. It’s a pleasure to be here with all of you. My name is Aaron Gerds and I’m an associate professor of medicine and the lead for our patients with myelofibrosis and MPNs [myeloproliferative neoplasms] at the Cleveland Clinic Taussig Cancer Center.

John Mascarenhas, MD: Thanks for joining us, Aaron. Raajit?

Raajit Rampal, MD, PhD: Hi, John. It’s good to be here with everybody. I’m Raajit Rampal. I’m an associate member and the acting chief of leukemia service at Memorial Sloan Kettering Cancer Center [in New York, New York], and I’m actively involved in investigations of clinical agents in MPNs.

John Mascarenhas, MD: Welcome, Raajit. Srdan?

Srdan Verstovsek, MD, PhD: Thank you, John. Hello, everybody. It’s a pleasure to join. I’m Srdan Verstovsek, a professor of medicine in the leukemia department at [The University of Texas] MD Anderson Cancer Center in Houston, Texas, where I’m a director of the [Hanns A. Pielenz] Clinical Research Center for Myeloproliferative Neoplasms.

John Mascarenhas, MD: Thanks for joining us, Srdan, and thank you all for participating. We met a few months ago and discussed the myelofibrosis landscape at that time. We’re going to talk about where we are now. We’ll review 2 patient scenarios, share our insights, and discuss recent updates in the treatment of patients with myelofibrosis. Let’s begin.

How is myelofibrosis diagnosed? What are some of the challenges faced when diagnosing patients? How do you risk-stratify patients with myelofibrosis? Srdan, I’ll ask you to start with this question.

Srdan Verstovsek, MD, PhD: The myelofibrosis diagnosis depends on a very good bone marrow sample. You need to have a bone marrow biopsy done. You can’t do it without the biopsy. You have to show the involvement of the bone marrow with the disease. This is where we have the first challenge. Many times, the sample isn’t very good. Even if it’s good, sometimes it’s confusing. In some patients, there aren’t too many fibers. There are some patients with no fibers, even when we [diagnose] them [as having] prefibrotic myelofibrosis.

A biopsy needs to be done, and you look at those fibers with different colors. You look at the percentage of the blasts, which are perhaps related to the aggressiveness of the disease, and you send the sample for analysis of chromosomes that have a prognostic importance, which I’m going to talk about in a second. You combine this with the findings in the blood. You look at the blood cell count and anemia. You look at the left shift or look for leukoerythroblastosis, the presence of bone marrow cells in the blood. You look at elevation in chemistry, a test called LDH, lactate dehydrogenase. You look at the enlargement of the spleen. You look at the symptoms. You have criteria to fulfill, which would call for a clinician to put this together. It’s a bone marrow finding with the chemistry, physical exam, and blood cell count that all comes down to whether there’s myelofibrosis.

The difficulties include not only the sampling of the bone marrow but also combining all this. Genetic testing on JAK2, calreticulin, or MPL is part of the diagnostic process. That may not be available. The sample may be poor, or the sensitivity of the test might not be there and you have triple-negative disease where you’re confused. Is this really myelofibrosis? Perhaps it’s MDS [myelodysplastic syndromes] with fibrosis. Differential [diagnosis] comes in. Expertise certainly counts when you have questions about fulfilling the diagnostic criteria.

Once you’re done with diagnosis, you go to prognostication. You want to know who has a life expectancy of less than 5 years. You’d refer that patient to a transplanter to go through a transplant procedure if possible to save the patient’s life, because that’s a justifiable procedure in that case. You would account for parameters, some of those that you got from the workup for diagnosis: degree of anemia, blasts in the blood, and symptoms. There are some others that would lead you to do more testing, NGS [next-generation sequencing] testing for the presence or absence of other nondriver mutations, including what I mentioned earlier about cytogenetic chromosomal analysis into prognostication.

There are a variety of prognostic scoring systems, 7 or 8 that are listed in the NCCN [National Comprehensive Cancer Network] guidelines, which you can apply…for the patients you’re looking at, depending on the results of the different tests you may have. The goal is to identify patients who will do worse than others, to refer them to transplant.

John Mascarenhas, MD: Srdan, beautifully put together. Out of curiosity, which of the risk stratification tools do you typically use?

Srdan Verstovsek, MD, PhD: At the first visit, the simpler, old-fashioned ones—IPSS [International Prognostic Scoring System] or DIPSS [Dynamic IPSS]—are the rule because they’re simpler in the sense that you’ll look at the blast, basically blood count symptoms, and you don’t need to have extensive genetic testing or chromosomal analysis done at the first visit. You don’t even have those results. When you do the testing at the subsequent visit, you may be more precise by incorporating more complex prognostic scoring systems with those genetic or karyotypic abnormalities to enhance your prediction of the future.

Transcript edited for clarity.

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