Case Studies in Myeloproliferative Neoplasms - Episode 9
Dr Jamile Shammo reviews the case of a 72-year-old man with primary myelofibrosis.
Ruben Mesa, MD: We recognize that myelofibrosis, in many ways, is the most challenging of the MPNs [myeloproliferative neoplasms]. It is the rarest but the most life-threatening and frequently the most impactful for individuals. Jamile, why don’t you take us through a case with high-risk myelofibrosis?
Jamile M. Shammo, MD: A 72-year-old man presented to his physician complaining of intermittent abdominal pain and 6 months of unexplained weight loss. We don’t know exactly how much weight loss. The spleen was palpable at 7 cm below the left costal margin. I’m impressed that someone still knows how to palpate spleens. A CBC [complete blood count] was done, and because of the results, the patient was referred to hematology for evaluation. To the right, you’ll see the CBC results. Hemoglobin was 10 g/dL; hematocrit was 39%; white blood cell count was high, 33,000 per mm3; platelets were 101,000 per mm3; and there were 3% blasts in the peripheral blood. The peripheral blood smear demonstrated leukoerythroblastic picture with nucleated threads and immature cells in the periphery. JAK2 V617F mutational analysis was positive. The hematologist decided to do a bone marrow biopsy, which was remarkable for megakaryocytic proliferation with some atypia, and the reticulin stain was positive for 3+ reticulin fibrosis. Therefore, with the anemia, the presence of megakaryocytic proliferation, and 3+ reticulin fibrosis—let’s assume that the BCR-ABL, or the Philadelphia chromosome, was negative. You have now met the criteria for diagnosis of primary myelofibrosis.
Ruben Mesa, MD: I’m mindful that, as we discussed in PV [polycythemia vera], we need an accurate diagnosis, prognosis, and assessment of disease burden to come up with our treatment plan. Stephen, why don’t you walk us through this. What does that beginning part look like as you’re working the patient up, doing the bone marrow biopsy, using risk assessment tool, and coming to the diagnosis? Before we pivot and talk about therapy, how do you assess where they stand?
Stephen Oh, MD, PhD: It’s quite obvious, but in the initial work-up of myelofibrosis, the absolutely key part of that is the bone marrow biopsy. As Prithviraj [Bose] outlined with PV, we know that a bone marrow biopsy is 1 of the major criteria. Here, if anything, it’s even more important. You have to do the bone marrow biopsy to establish the diagnosis. You have to demonstrate that you see the megakaryocyte, atypia, and the characteristic reticulin fibrosis. Sometimes we’re surprised. In fact, when we do the bone marrow biopsy, it sometimes points us in a different direction. Some cases you see trilineage dysplasia, and it turns out that it’s MDS [myelodysplastic syndromes] and not myelofibrosis. Bone marrow is key.
One other key part of the work-up is testing for the 3 common driver mutations: JAK2, CALR, and MPL. The vast majority of patients with myelofibrosis are going to be positive for 1 of those 3. There is also a subset of patients in that triple-negative category, so even if all 3 mutations are absent, it does not rule out a diagnosis of myelofibrosis. But the majority are going to be positive for 1 of 3.
As you gain this information for an individual patient, you confirm the diagnosis of myelofibrosis and then begin to think about risk stratification and prognosis. There are a variety of different prognostics, scorings, and schemes that can be utilized. Some were developed specifically for at diagnosis only, and others can be used at any point in the disease course—as well as some distinction between primary myelofibrosis or post-PV or post–ET [essential thrombocythemia] myelofibrosis. I tend to use the MIPSS70+ [Mutation-Enhanced International Prognostic Scoring System 70+] for patients with primary myelofibrosis. That allows me to incorporate a variety of clinical features as well as molecular features, including JAK2, CALR status, as well as high-molecular-risk mutations such as ASXL1, SRSF2, etc. That tends to be the tool that I use most commonly these days to risk stratify patients with myelofibrosis.
This transcript has been edited for clarity.