During a live event, Karen Seiter, MD, discussed the role of the JAK/STAT pathway in myeloproliferative neoplasms and the use of ruxolitinib to treat myelofibrosis.
Karen Seiter, MD
Professor of Medicine
New York Medical College
Director of the Adult Leukemia Service
Westchester Medical Center
Valhalla, NY
CASE SUMMARY
- A 68-year-old woman presented to her physician with symptoms of mild fatigue.
- Spleen was palpable 6 to 7 cm below the left costal margin
- Past medical history: no known comorbidities
- Next-generation sequencing testing: JAK2 V617F mutation
- Karyotype: 46,XX
- Bone marrow biopsy: megakaryocyte proliferation and atypia with evidence of reticulin fibrosis
- Blood smear: leukoerythroblastosis
- Diagnosis: primary myelofibrosis
Risk
- Dynamic International Prognostic Scoring System: intermediate-1
- Mutation-Enhanced International Prognostic Scoring System for Transplantation-Age Patients: intermediate risk
Laboratory Values
- Red blood cell count: 3.40 ×106/μL
- Hemoglobin level: 9.7 g/dL
- Hematocrit: 32.3%
- Mean corpuscular volume: 94 μm3
- White blood cell count: 23,000/μL
- Platelet count: 450,000/μL
- Peripheral blood blasts: <1%
Peers & Perspectives in Oncology: What disease states are currently classified as myeloproliferative neoplasms (MPNs)?
Seiter: The latest classification is the 2022 World Health Organization [WHO] classification.1,2 As a clinician, when we have myeloproliferative diseases, we think of MPNs [as meaning the patient] has too much of something: The WBC count is too high but with maturing myeloid and not with a lot of blasts, or the hemoglobin [level] is too high, or the [platelet count is] too high. That would be potentially chronic myelocytic leukemia [CML], polycythemia vera [PV], essential thrombocytopenia [ET], and for primary myelofibrosis, the most common presentation would be somebody with either anemia, with abdominal distension or early satiety from splenomegaly. The WBC count could be high; it could be low; platelets could be high, or they could be low.
When we’re working up patients with MPN, the first step is always to make sure that they don’t have CML, because CML can look like myelofibrosis because CML can present with a high platelet count. The first step is always to [test for] the Philadelphia chromosome and perform BCR::ABL1 testing to make sure it’s not CML.
Most of these patients are going to have a bone marrow [biopsy] done. There’s always the debate about, if you have somebody with a hemoglobin level of 20 g/dL, where it looks pretty clear that they have PV, do you need a bone marrow [biopsy] in order to formally diagnose the patient? You do because that’s part of the diagnostic criteria. But sometimes, if you have a much older patient with frailty, you have to consider the goals of care. Sometimes, there may be cases of patients who don’t get the bone marrow biopsy done. The only time it would be reasonable is if the hemoglobin level is high; for anything else, there are so many other things that [it] could be that it’s important to do the bone marrow biopsy for a diagnosis.
Mastocytosis used to be [listed among the] MPNs, but [the WHO] made it its own classification. MPNs with eosinophilia are a separate category. Now we have the myelodysplastic syndrome [MDS]/MPN overlap; that’s a separate category. Then, we have MDS, secondary myeloid neoplasms, and acute myeloid leukemia.