A Case of Uncontrolled Polycythemia Vera


Expert Prithviraj Bose, MD, reviews standard practices in diagnosing and risk stratifying uncontrolled polycythemia vera in the context of a patient case.


Prithviraj Bose, MD: Hi, and welcome to this Targeted Oncology™ program on case-based peer perspectives. Today’s topic is polycythemia vera [PV]. I’m Prithviraj Bose. I’m part of the leukemia faculty at [The University of Texas] MD Anderson [Cancer Center] in Houston, Texas. We’re going to start with the case of a 60-year-old man with uncontrolled PV, and then we’ll get into some of the discussion around the points that the case brings up.

This is a 60-year-old gentleman who presented in March 2020 with frequent itching, dizziness, and headache. Labs revealed a hemoglobin of 20 g/dL, hematocrit of 61%, an MCV [mean corpuscular volume] of 82 µm3, a white blood cell count of 11 per mm3, and a platelet count of 391 per mm3. The bone marrow revealed trilineage proliferation and pleiomorphic megakaryocytes. Molecular testing revealed the JAK2 V617F mutation, and the allele burden was 69%. The patient was diagnosed with polycythemia vera and was started on a baby aspirin, 81 mg per day, and phlebotomies.

In June 2020, 3 months after the diagnosis, the patient was seen again. He had had 3 phlebotomies in the prior 3 months and had continued symptoms. At that point, 1 g per day of Hydrea was added to the treatment plan. Fast-forward to September, 6 months after he was diagnosed, and he had had 6 phlebotomies since his visit in March. At this point, the hydroxyurea dose was increased to 1500 mg per day. In December, 9 months from his initial diagnosis, the patient was still dependent on phlebotomy. He a new complaint of pruritis, an emergent itching issue. The hydroxyurea at this point was increased to 2000 mg per day: 4 pills, 2 g per day.

In March 2021, a full year after he was initially diagnosed, he was still requiring phlebotomies. At this point, he started to complain of fullness after eating, an early satiety situation. The spleen at this point was palpable: 7 cm below the left costal margin. Clearly, we have a patient who has PV. He is started with phlebotomies and aspirin, and then hydroxyurea is added. The dose is progressively increased because of the issues we went over. We are a year out from diagnosis, and the spleen is big, phlebotomy is still required, and there are persistent symptoms. With that, we’ll get into our discussion on PV, starting with the diagnosis and the presentation.

Polycythemia vera is the most common myeloproliferative neoplasm. The criteria to diagnose PV have been updated. There are new criteria as of 2016. There are 3 major criteria and only 1 minor criterion. The first major criterion are the hemoglobin and hematocrit thresholds, which are slightly different in men and women. In men, it’s 16.5 g/dL or higher [for the hemoglobin]; in women, it’s 16 or higher g/dL. The second criterion has to do with the bone marrow biopsy. This didn’t used to be a major criterion, but now it is. The bone marrow biopsy typically shows, as in our case, pleomorphic megs, a panmyelosis picture with all 3 cell lines increased, as in our patient. The third major criterion is the JAK2 V617F mutation, which is found in 95% of patients with PV; another 4% will have an exon 12 mutation.

Those are your 3 major criteria. There’s 1 minor criterion, which is a subnormal or low EPO [erythropoietin] level. What’s needed for diagnosis are all 3 major criteria, which would satisfy the requirement, or the first 2 major criteria and the minor criterion. The order of the major criteria matters. The first 2 would be the hemoglobin/hematocrit and the bone marrow, along with the minor criterion, which is low EPO. This provision is there for the 1% or so who may not have the JAK2 mutation. Otherwise, the majority are going to be able to fulfill all 3 major criteria: the hemoglobin/hematocrit thresholds, the classic bone marrow appearance, and the JAK2 mutation.

Coming back to this patient, 1 of the first questions we face after we know the PV diagnosis, is what is the risk stratification? This patient 60 years old, but I would call this patient high risk, because we have traditionally considered 60 and older to be high risk, with younger than 60 being low risk. Regardless of age, if they’ve had a history of thrombosis, that makes them high risk. That wasn’t mentioned in our case. We’ll go just with the age, but because he’s 60, I’d call this a high-risk patient. The risk stratification hasn’t evolved, although there’s a lot of new information on the importance of white blood cells and how that may impact thrombotic risk and other risks. But the conventional risk stratification remains the simplistic classification based on age and prior thrombosis.

Transcript edited for clarity.

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