Thrombosis, Myelofibrosis, and Acute Myeloid Leukemia

Prithviraj Bose, MD:In PV [polycythemia vera], the goal of treatment really has centered on preventing thrombosis, and this is driven by the fact that PV patients have a prolonged survival, inferior to that of the age- and sex-matched population, however. So they don’t have a normal survival, but they have a good survival. And because of that, the focus really has been on preventing thrombosis and also bleeding, to a lesser extent. So really the whole goal of management in a big way is to prevent thrombosis.

There is unfortunately a risk of progression to MF [myelofibrosis] in all patients with PV. There is always some risk, as well as of transformation to AML [acute myeloid leukemia], which could happen straight from PV or with an intervening MF phase. The risks are low, but we have estimates of about 10 or 15 years. And over, say, a 15-year period, you could have something like a 5% to 7% risk of developing myelofibrosis and a smaller one of developing AML. There are some risk factors for these things that have been identified. For example, if you have fibrosis at the very beginning, at the very outset in your marrow, then you have a higher risk of developing post-PV MF. For AML, there have again been a number of risk factors identified. One of them has been exposure to multiple cytotoxic drugs. Fortunately, we don’t see that much anymore, but in the past, patients who had multiple alkylating agents had a higher risk.

We did say that this patient is low-risk because she’s under age 60 and has never had a clot. And while that is sort of the correct onset if it were on a test, there are other features that we need to look at. This patient, for example, has some leukocytosis, which we are increasingly concerned about because there seems to be a correlation with thrombosis as well as worse survival in patients who have leukocytosis. That has actually been shown in a number of studies that have linked white blood cell counts 11 and higher to both worse survival and a higher risk of thrombosis. While patients with low-risk PV are typically managed with phlebotomy and aspirin, there are a few other indicators of initiating cytoreductive therapy that are recognized in guidelines, such as the NCCN [National Comprehensive Cancer Network] Guidelines. And some of those are frequent phlebotomy requirements, progressive leukocytosis, symptomatic thrombocytosis, splenomegaly that’s symptomatic and is not really responding, and things of that nature.

Transcript edited for clarity.

Case: 58-Year-Old Woman Diagnosed With Polycythemia Vera

November 2018

• A 58-year old woman presents to PCP complaining of abdominal pain, dizziness and headaches
• PE: BP 140/85; Splenomegaly ~6 cm below left costal margin
• PMH: No prior history of thrombosis
• Lab values:
  • HGB: 17.1 g/dL
  • Hct: .50 L/L
  • RBC: 71 x 10¹²/L
  • WBC: 13.2 x 10⁹/L
  • Serum EPO: 4.1 mU/mL
• Bone Marrow Biopsy: Erythroid hyperplasia
• Cytogenetics: JAK-V617Fmutation