Managing the Risk of Thrombosis

Maintaining Hematocrit (Hct) Level <45% Was Evaluated in a Randomized Clinical Study (Marchioli et al, 2013)1

The CYTO-PV trial was a randomized clinical trial that examined risk for cardiovascular death or major thrombosis associated with specific hematocrit levels in patients with polycythemia vera (PV).

The study included 365 adult patients with PV being treated with phlebotomy, hydroxyurea (HU), or both.

Patients were randomized into one of two groups with different target Hct levels.

  • One group received more aggressive treatment for an Hct target less than 45% (low-Hct group), and the other group received less aggressive treatment for an Hct target of 45% to 50% (high-Hct group)
  • The composite primary endpoint was the time until cardiovascular death or major thrombotic events
  • Therapy options for maintaining Hct levels within the respective treatment groups were phlebotomy, cytoreductive drugs, or both
  • Baseline characteristics were balanced between both groups
  • ≈50% had received an initial diagnosis of PV within 2 years before enrollment
  • 67.1% were at high risk because of age ≥65 or previous thrombosis
Image of chart showing the probability of remaining event free in the CYTO-PV study (N=365)
 
In a multivariable, time-dependent analysis, the results indicate the risk of thrombosis was increased in patients with a WBC count >7 × 109/L (ie, HR >1), becoming statistically significant at WBC >11 × 109/L HR=3.90 (95% CI: 1.24-12.3); P=0.022
Kaplan-Meier curves for primary composite endpoint. Adapted with permission from the Massachusetts Medical Society. CI, confidence interval; Hct, hematocrit; HR, hazard ratio; WBC, white blood cell.

Additional Analysis From the CYTO-PV Study

Elevated WBC Counts >11 × 109/L Increased the Risk of Thrombosis2

  • In a multivariable time-dependent analysis, WBC counts >11 × 109/L were associated with increased risk of thrombosis (HR, 3.9; 95% CI, 1.24-12.3; P = 0.02)2
  • In this analysis, there was a trend for increased risk of thrombosis with WBC count >7 × 109/L (ie, HR >1) that became statistically significant in patients with WBC counts >11 × 109/L2
  • These results are consistent with other literature that suggests leukocytosis may increase the risk of thrombosis3,4
Image of chart showing Time-dependent Mulitivariable Analysis on the Risk of Major Thrombosis in (CYTO-PV) study
*Adjusted for age, gender, cardiovascular risk factors, previous thrombosis, and Hct levels.2

REVEAL Study

In a Prospective, Observational Study, Some Patients Continued to Have Elevated Counts, Despite Treatment With HU5

  • The median of the maximum Hct value among evaluable patients (n=1106) who received HU for ≥3 months was6:
    • 48.3% for those who reported a value >45%
    • 42% for those who reported a value ≤45%

Patients Who Were Treated With HU and Receiving Phlebotomy (PBT) Were More Likely to Have Elevated Blood Counts6

  • After 3 months of HU, 32.9% (457/1390) of patients continued to undergo PBTs6
    • Of 414 evaluable patients who received a PBT after 3 months of HU, 82.9% continued to have Hct >45%
Chart showing Elevated laboratory values by PBT 3 months of enrollment and HU exposure
References

1. Marchioli R, Finazzi G, Specchia G, et al; for the CYTO-PV Collaborative Group. N Engl J Med. 2013;368(1):22-33. 2. Barbui T, Masciulli A, Marfisi MR, et al. Blood. 2015;126(4):560-561. 3. Gangat N, Strand J, Li CY, Wu W, Pardanani A, Tefferi A. Br J Haematol. 2007;138(3):354-358. 4. Landolfi R, Di Gennaro L, Barbui T, et al. Blood. 2007;109(6):2446-2452. 5. Grunwald MR, Burke JM, Kuter DJ, et al. Clin Lymphoma Myeloma Leuk. 2019;19(9):579-584.e1. 6. Grunwald MR, Altomare I, Burke JM, et al. Poster presented at: 59th Annual Meeting and Exposition of the American Society of Hematology; December 9–12, 2017; Atlanta, GA.

 
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