Expert Insights

Part 3: Elevated White Blood Cell Count and Thrombotic Risk

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Narrator: Clinical characteristics of advanced PV may include hematocrit greater than or equal to 45% plus one additional risk factor despite treatment with hydroxyurea and phlebotomy. Specifically, clinical characteristics of advanced PV may include hematocrit greater than or equal to 45% plus elevated white blood cell count greater than 11x109 per liter or burdensome disease-related symptoms such as fatigue, early satiety, inactivity, concentration problems, and itching.

Dr Shammo: The CYTO-PV study was a prospective, randomized study of patients who have PV with the idea of identifying the appropriate hematocrit cutoff level as it relates to the risk of thrombotic events, primarily fatal cardiovascular events and major thrombosis.

Narrator: In the Cytoreductive Therapy in Polycythemia Vera (CYTO-PV) study of 365 adult patients with PV treated with phlebotomy, hydroxyurea, or both, patients were randomized to 1 of 2 groups—either the low-Hct group (with more intensive therapy to maintain a target Hct level less than 45%) or the high-Hct group (with less intensive therapy to maintain a target Hct level of 45% to 50%).

The composite primary end point was the time until cardiovascular death or major thrombosis.

Baseline characteristics were balanced between the groups. Approximately 50% of patients had received an initial diagnosis of PV within 2 years prior to randomization. 67.1% of patients (n = 245) were at high risk because of age greater than or equal to 65 years or previous thrombosis.

Dr Shammo: There was a retrospective analysis of the CYTO-PV data that was conducted to answer the question as to whether leukocytosis represents another risk factor for thrombosis as has been the case in prior retrospective evaluations.

But for the CYTO-PV study in particular, to separate the impact of leukocytosis from the high hematocrit, the investigators looked at a specific statistical model that they utilized in order to drive that point. And that was called "multivariate time dependent analysis" which evaluated in 4 different quartiles, the type of leukocytosis this patient had, and the propensity or the risk of developing a thrombotic event.

And it appeared that patients who had white cell count greater than 11,000 had 4-times higher likelihood of developing a thrombotic event compared to those who had a white cell count around 7,000. And this too, was statistically significant.

Narrator: Actively monitor for hematocrit plus in your patients with polycythemia vera.

Image of Jamile M Shammo, MD, FASCP, FACP
Jamile M Shammo, MD, FASCP, FACP Associate Professor Rush University Medical Center | Chicago, IL
As principal investigator of clinical trials in her area of expertise, Dr Shammo is heavily involved in education, research, and administrative activities in the Division of Hematology/Oncology. She is recognized nationally for her expertise in bone marrow failure syndromes/paroxysmal nocturnal hemoglobinuria (PNH) and was chosen to serve as a national coordinator for the US PNH registry.